| 51. |
- Eleftheriadis, Georgios K., et al.
(författare)
-
Automated digital design for 3D-printed individualized therapies
- 2021
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 599
-
Tidskriftsartikel (refereegranskat)abstract
- Customization of pharmaceutical products is a central requirement for personalized medicines. However, the existing processing and supply chain solutions do not support such manufacturing-on-demand approaches. In order to solve this challenge, three-dimensional (3D) printing has been applied for customization of not only the dose and release characteristics, but also appearance of the product (e.g., size and shape). A solution for customization can be realized via non-expert-guided processing of digital designs and drug dose. This study presents a proof-of-concept computational algorithm which calculates the optimal dimensions of grid-like orodispersible films (ODFs), considering the recommended dose. Further, the algorithm exports a digital design file which contains the required ODF configuration. Cannabidiol (CBD) was incorporated in the ODFs, considering the simple correspondence between the recommended dose and the patient's weight. The ODFs were 3D-printed and characterized for their physicochemical, mechanical, disintegration and drug release properties. The algorithm was evaluated for its accuracy on dose estimation, highlighting the reproducibility of individualized ODFs. The in vitro performance was principally affected by the thickness and volume of the grid-like structures. The concept provides an alternative approach that promotes automation in the manufacturing of personalized medications in distributed points of care, such as hospitals and local pharmacies.
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| 52. |
- Elversson, J, et al.
(författare)
-
Aqueous two-phase system as a formulation concept for spray-dried protein
- 2005
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 294, s. 73-87
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates to what extent an aqueous two-phase system (ATPS) can encapsulate and protect the secondary structure of a protein during spray drying. The ATPSs contained polyvinyl alcohol (PVA) and dextran solutions, in different proportions. A model protein, bovine serum albumin (BSA) and, in some experiments, trehalose were added to the ATPS prior to spray drying. Electron spectroscopy for chemical analysis (ESCA), differential scanning calorimetry (DSC), UV spectrophotometry, size exclusion high-performance liquid chromatography (SEC-HPLC) and Fourier transform infrared spectroscopy (FTIR) were used for analysis of solid and reconstituted samples. The anticipated function of the ATPS was to improve the stability of the protein by preventing interactions with the air–liquid interface during drying and by improving the encapsulation of the protein in the dried powder. BSA was found to preferentially partition to the dextran phase and in the absence of PVA, BSA dominated the powder surface. In samples containing PVA, the polymer mainly covered the powder surface, even though the dextran-rich phase was continuous, thus preventing protein surface interactions and providing improved encapsulation. However, PVA was found to cause partial loss of the native structure of BSA although the protein was well encapsulated during spray drying
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| 53. |
- Elversson, Jessica, et al.
(författare)
-
In situ coating : an approach for particle modification and encapsulation of proteins during spray-drying
- 2006
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 323:1-2, s. 52-63
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present a method for in situ coating of individual protein particles in a respirable size. The aim of the coating was to influence the particle/powder properties, and to reduce or prevent surface-induced conformational changes of the protein, during spray-drying, which was the method used for simultaneously preparing and coating particles. The investigated formulations included bovine serum albumin (BSA), trehalose and either of the two non-ionic polymers, hydroxypropyl methylcellulose (HPMC) and poly(ethylene oxide)–poly(propylene oxide) triblock co-polymer (Poloxamer 188). Complete protein coating as measured by electron spectroscopy for chemical analysis (ESCA) was achieved at a polymer concentration of approximately 1% of the total solids weight, and could be predicted from the dynamic surface tension at the air/water interface, as measured by the pendant drop method. Further, particle properties such as: size, dissolution time, powder flowability, and apparent particle density, as measured by gas pycnometry, were affected by the type and concentration of the polymer. In addition, the particle surface morphology could possibly be correlated to the surface elasticity of the droplet surface during drying. Moreover, an extensive investigation (Fourier transform infrared spectroscopy, circular dichroism and size exclusion chromatography) of the structural effects of protein encapsulated in a polymeric coating suggested that in situ coating provide particulate formulations with preserved native conformation and with a high stability during rehydration.
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| 54. |
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| 55. |
- Evenbratt, Hanne, 1980, et al.
(författare)
-
In vivo study of an instantly formed lipid-water cubic phase formulation for efficient topical delivery of aminolevulinic acid and methyl-aminolevulinate
- 2013
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 452:1-2, s. 270-275
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1 g cubic phase in less than 1 min confirmed by X-ray diffraction, consisting of an ether lipid, 1-glyceryl monooleyl ether (GME), an aprotic solvent (propylene glycol or pentane-1,5-diol) and water. The efficacy of the cubic formulation was tested in vivo by administrating formulations containing 3% (w/w) of the HCl salts of delta-aminolevulinic acid (ALA) or methylaminolevulinate (MAL) to hairless mice. The endogenous formation of protoporphyrin IX (PpIX) was monitored spectrophotometrically as a marker for cellular uptake of active compound. As reference, a commercial product containing 16% (w/w) MAL in an oil-in-water emulsion (Metvix (R)), and a cubic phase based on an ester lipid (glyceryl monooleate, GMO), previously shown to facilitate topical delivery of both ALA and MAL, were applied. It was found that in general the cubic phases gave rise to higher fluorescence levels than the mice exposed to the commercial product. The instantly formed cubic formulations based on GME demonstrated the same efficiency as the GMO based formulations. The results imply that instantly formed cubic formulations opens up new opportunities, particularly for transdermal drug delivery of substances subject to stability problems in, e. g. aqueous environments.
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| 56. |
- Fadda, Hala M, et al.
(författare)
-
Intra- and inter-subject variability in gastric pH following a low-fat, low-calorie meal
- 2022
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 625
-
Tidskriftsartikel (refereegranskat)abstract
- Food can alter drug bioavailability through gastric pH changes. Time spent at gastric pH ranges is reported here, including variability data following ingestion of a light, mixed, 260 kcal meal. pH data was obtained for 20 healthy subjects undergoing SmartPill™ wireless motility capsule investigations on three separate visits. Gastric phase pH was sorted into pH < 2, 2-3, 3-4, 4-5 and > 5. All visits and all subjects were pooled to determine median time (25-75th percentiles) in minutes. Gastric emptying time was 176 (137-205) min with the majority of time, 111 (67 - 163), spent at pH < 2. Times spent at pH 2-3 and 3-4 were similar: 17 (5.7 - 35.6) and 18 (7.2-29.3). Time spent at pH 4-5 was 9 (1.3-20.6) and at pH > 5 was 0.7 (0-4.4). Intra-subject variability as determined by robust coefficient of variation (RCV)% was 30 % for pH < 2, 57 % for pH 2-3, 71 % for pH 3-4, 106 % for pH 4-5 and 144 % for pH > 5. Inter-subject variability RCV% was 49 % for pH < 2, 89 % for pH 2-3, 54 % for pH 3-4, 97 % for pH 4-5 and 148 % for pH > 5. Inter-subject variability can be up to approximately twofold higher than intra-subject variability at the lower pH ranges.
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| 57. |
- Fager, Cecilia, 1990, et al.
(författare)
-
3D high spatial resolution visualisation and quantification of interconnectivity in polymer films
- 2020
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier B.V.. - 0378-5173 .- 1873-3476. ; 587
-
Tidskriftsartikel (refereegranskat)abstract
- A porous network acts as transport paths for drugs through films for controlled drug release. The interconnectivity of the network strongly influences the transport properties. It is therefore important to quantify the interconnectivity and correlate it to transport properties for control and design of new films. This work presents a novel method for 3D visualisation and analysis of interconnectivity. High spatial resolution 3D data on porous polymer films for controlled drug release has been acquired using a focused ion beam (FIB) combined with a scanning electron microscope (SEM). The data analysis method enables visualisation of pore paths starting at a chosen inlet pore, dividing them into groups by length, enabling a more detailed quantification and visualisation. The method also enables identification of central features of the porous network by quantification of channels where pore paths coincide. The method was applied to FIB-SEM data of three leached ethyl cellulose (EC)/hydroxypropyl cellulose (HPC) films with different weight percentages. The results from the analysis were consistent with the experimentally measured release properties of the films. The interconnectivity and porosity increase with increasing amount of HPC. The bottleneck effect was strong in the leached film with lowest porosity.
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| 58. |
- Ferreira, Magda, et al.
(författare)
-
Levofloxacin-loaded bone cement delivery system : highly effective against intracellular bacteria and Staphylococcus aureus biofilms
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 532:1, s. 241-248
-
Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a major pathogen in bone associated infections due to its ability to adhere and form biofilms on bone and/or implants. Moreover, recrudescent and chronic infections have been associated with S. aureus capacity to invade and persist within osteoblast cells. With the growing need of novel therapeutic tools, this research aimed to evaluate some important key biological properties of a novel carrier system composed of acrylic bone cement (polymethylmethacrylate – PMMA), loaded with a release modulator (lactose) and an antibiotic (levofloxacin).Levofloxacin-loaded bone cement (BC) exhibited antimicrobial effects against planktonic and biofilm forms of S. aureus (evaluated by a flow chamber system). Moreover, novel BC formulation showed high anti-bacterial intraosteoblast activity. This fact led to the conclusion that levofloxacin released from BC matrices could penetrate the cell membrane of osteoblasts and be active against S. aureus strains in the intracellular environment. Furthermore, levofloxacin-BC formulations showed no significant in vitro cytotoxicity and no allergic potential (measured by the in vivo chorioallantoic membrane assay). Our results indicate that levofloxacin-loaded BC has potential as a local antibiotic delivery system for treating S. aureus associated bone infections.
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| 59. |
- Fichtner, Frauke, et al.
(författare)
-
Effect of preparation method on compactability of paracetamol granules and agglomerates
- 2007
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 336:1, s. 148-158
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the effect of fracture strength of paracetamol particles on their compactability. For this purpose two series of paracetamol particles were prepared by crystal agglomeration and by granulation using different solvents. A free flowing particle size fraction of all types of particles was characterized with respect to their shape, degree of agglomeration and single fracture strength. The powders were compressed to tablets and the compression mechanism of the particles and the evolution in tablet micro-structure were assessed by compression parameters derived from the Heckel and Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile strength and porosity were determined. The degree of deformation and fragmentation during compression varied between agglomerates and granules and was dependent on their failure strength. The granules varied in compactability with particle failure strength while the agglomerates showed limited variation. It is proposed that, the dominant mechanism of compression for the granules was permanent deformation while for the agglomerates it was fragmentation. It was thus found that the compression mechanism of the particles was dependent on both the degree of agglomeration and the particle failure strength.
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| 60. |
- Fichtner, Frauke, et al.
(författare)
-
Particle size distribution and evolution in tablet structure during and after compaction
- 2005
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 292:02-jan, s. 211-225
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the effect of the distribution in size of free-flowing particles for the evolution in tablet structure and tablet strength. For sucrose and sodium chloride, three powders of different size distributions were prepared by mixing predetermined quantities of particle size fractions. For paracetamol, three batches with varying particle size distributions were prepared by crystallisation. The powders were formed into tablets. Tablet porosity and tensile strength were determined directly after compaction and after short-term storage at two different relative humidities. Tablets were also formed after admixture of a lubricant (magnesium stearate) and the tablet tensile strength was determined. For the test materials used in this study, the spread in particle size had no influence on the evolution in tablet porosity and tensile strength during compression. However, the spread in particle size had a significant and complex influence on the short-term post-compaction increase in tablet tensile strength. The effect of the spread was related to the instability mechanism and the presence of lubricant. It is concluded that the distribution in size of free-flowing particles is not critical for the tablet porosity but may give significant effects on tablet tensile strength due to a post-compaction reaction.
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| 61. |
- Fonteyne, Margot, et al.
(författare)
-
Impact of microcrystalline cellulose material attributes : A case study on continuous twin screw granulation
- 2015
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 478:2, s. 705-717
-
Tidskriftsartikel (refereegranskat)abstract
- The International Conference on Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of material attributes, manufacturing process options and process parameters. The present case study evaluates the effect of unspecified variability of raw material properties upon the quality attributes of granules; produced using a continuous from-powder-to-tablet wet granulation line (ConsiGma (TM) 25). The impact of different material attributes of six samples of microcrystalline cellulose (MCC) was investigated. During a blind study the different samples of MCC were used separately and the resulting granules were evaluated in order to identify the differences between the six samples. Variation in size distribution due to varying water binding capacity of the MCC samples was observed. The cause of this different water binding capacity was investigated and was caused by a different degree of crystallinity. Afterwards, an experimental design was conducted in order to evaluate the effect of both product and process variability upon the granule size distribution. This model was used in order to calculate the required process parameters to obtain a preset granule size distribution regardless of the type of MCC used. The difference in water binding capacity and its effect on granular properties was still present when combining the MCC grades with different binders.
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| 62. |
- Fredenberg, Susanne, et al.
(författare)
-
Development of mass transport resistance in poly(lactide-co-glycolide) films and particles - A mechanistic study.
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 409:1-2, s. 194-202
-
Tidskriftsartikel (refereegranskat)abstract
- Poly(d,l-lactide-co-glycolide) (PLG) is the most frequently used biodegradable polymer in the controlled release of an encapsulated drug. The purpose of this work was to explain the surprisingly slow diffusion through this polymer, and locate the major source of mass transport resistance. Diffusion of human growth hormone (hGH) and glucose through PLG films was undetectable (using a diffusion cell), although the degraded polymer contained several times more water than polymer mass. In vitro release of hGH from PLG-coated particles also showed a surprisingly slow rate of release. Non-porous regions inside the PLG films were detected after three weeks of degradation using dextran-coupled fluorescent probes and confocal microscopy. The findings were supported by scanning electron microscopy. Diffusion through PLG films degraded for five weeks was significantly increased when the porosity of both surfaces was increased due to the presence of ZnCl(2) in the buffer the last 3 days of the degradation period. The results indicated high mass transport resistance inside the films after three weeks of degradation, and at the surfaces after five weeks of degradation. These results should also be applicable to microparticles of different sizes. Knowledge of the reason for transport resistance is important in the development of pharmaceuticals and when modifying the rate of drug release.
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| 63. |
- Fredenberg, Susanne, et al.
(författare)
-
Encapsulated zinc salt increases the diffusion of protein through PLG films.
- 2009
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 370, s. 47-53
-
Tidskriftsartikel (refereegranskat)abstract
- The use of microspheres and nanospheres of poly(d,l-lactide-co-glycolide) (PLG) as a controlled-release drug delivery system has been the subject of great interest for at least two decades within the field of pharmaceuticals. Salts of zinc and other divalent cations are sometimes co-encapsulated in PLG particles to control the pH or to stabilize encapsulated proteins or peptides. Zinc salts are known to affect pore formation and other processes that may lead to the release of an encapsulated drug. In this study the effect of encapsulated zinc acetate on protein diffusion through PLG films was investigated. PLG films, with and without encapsulated zinc acetate, were degraded in Hepes buffer for different periods of time. The films were subsequently subjected to various kinds of analyses: diffusion properties (using a diffusion cell), porosity (using scanning electron microscopy) and thickness (using light microscopy and an image-analysis program). Encapsulated zinc acetate had a considerable effect and increased the diffusion coefficient of lysozyme through PLG films degraded for 18 days or longer. Films containing zinc acetate became porous, while those without zinc acetate only developed cavities on the surface. Zinc salts may thus be used as release-modifying agents. This effect should be considered when using zinc salts as protein stabilizers or pH neutralizers.
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| 64. |
- Fredenberg, Susanne, et al.
(författare)
-
The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-A review.
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 415:1-2, s. 34-52
-
Tidskriftsartikel (refereegranskat)abstract
- Poly(d,l-lactic-co-glycolic acid) (PLGA) is the most frequently used biodegradable polymer in the controlled release of encapsulated drugs. Understanding the release mechanisms, as well as which factors that affect drug release, is important in order to be able to modify drug release. Drug release from PLGA-based drug delivery systems is however complex. This review focuses on release mechanisms, and provides a survey and analysis of the processes determining the release rate, which may be helpful in elucidating this complex picture. The term release mechanism and the various techniques that have been used to study release mechanisms are discussed. The physico-chemical processes that influence the rate of drug release and the various mechanisms of drug release that have been reported in the literature are analyzed in this review, and practical examples are given. The complexity of drug release from PLGA-based drug delivery systems can make the generalization of results and predictions of drug release difficult. However, this complexity also provides many possible ways of solving problems and modifying drug release. Basic, generally applicable and mechanistic research provides pieces of the puzzle, which is useful in the development of controlled-release pharmaceuticals.
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| 65. |
- Frenning, Göran, et al.
(författare)
-
Computational fluid dynamics (CFD) studies of a miniaturized dissolution system
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 521:1-2, s. 274-281
-
Tidskriftsartikel (refereegranskat)abstract
- Dissolution testing is an important tool that has applications ranging from fundamental studies of drugrelease mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400 rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400 rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen.
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| 66. |
- Frenning, Göran
(författare)
-
Modelling drug release from inert matrix systems : From moving-boundary to continuous-field descriptions
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 418:1, s. 88-99
-
Forskningsöversikt (refereegranskat)abstract
- The purpose of this review is to provide a comprehensive overview of mathematical procedures that can be used to describe the release of drugs from inert matrix systems. The review focuses on general principles rather than particular applications. The inherent multiscale nature of the drug-release process is pointed out and multiscale modelling is exemplified for inert porous matrices. Although effects of stagnant layers and finite volumes of release media are briefly discussed, the systematic analysis is restricted to systems under sink conditions. When the initial drug loading exceeds the drug solubility in the matrix, Higuchi-type moving-boundary descriptions continue to be highly valuable for obtaining approximate analytical solutions, especially when coupled with integral balance methods. Continuous-field descriptions have decisive advantages when numerical solutions are sought. This is because the mathematical formulation reduces to a diffusion equation with a nonlinear source term, valid over the entire matrix domain. Solutions can thus be effortlessly determined for arbitrary geometries using standard numerical packages.
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| 67. |
- Gautschi, Nicolas, et al.
(författare)
-
Rapid determination of drug solubilization versus supersaturation in natural and digested lipids
- 2016
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 513:1-2, s. 164-174
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations (LBFs) represent one of the successful formulation approaches that enable oral delivery of poorly water-soluble drugs. This work presents a simple equilibrium approach based on solubility in lipids and their corresponding digestion media to estimate a maximum drug supersaturation ratio (SRmax). This value of drug concentration normalized by the solubility in the aqueous digestion phase indicates the propensity for drug precipitation. A set of 16 structurally diverse drugs was first measured for their solubility in tricaprin and tricaprylin and results were compared to an empirical model based on molecular predictors. In the next step, digestion media were either prepared by in vitro lipolysis or by assembling a composition to mimic the endpoint of digestion. It was found that drug solubility in the pure lipids mainly was related to the melting point in that increased values resulted in reduced solubility. The solubility values measured in the lipolysis media correlated well with those obtained from assembled digestion media. Interestingly, the solubilization upon digestion was typically higher when using tricaprin than tricaprylin in spite of that the latter oil (as pure excipient) generally was a more potent solvent. This work suggests that a simplified digestion screen can be used to facilitate evaluation of formulations during early development. Estimation of SRmax provides an early risk assessment of drug precipitation for LBFs. The method is easily scaled down to the microtiter plate format and can be used for selecting candidate formulations that merit further evaluation in more complex and dynamic in vitro tests.
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| 68. |
- Govender, Rydvikha, 1989, et al.
(författare)
-
Enabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs
- 2021
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 602
-
Tidskriftsartikel (refereegranskat)abstract
- Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy.
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| 69. |
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| 70. |
- Hedenus, P, et al.
(författare)
-
Characterisation of instantaneous water absorption properties of pharmaceutical excipients.
- 2000
-
Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 202:1-2, s. 141-9
-
Tidskriftsartikel (refereegranskat)abstract
- Powders absorb water by both capillary imbibition and swelling. The capillary process is almost instantaneous but swelling occurs over a period of time. An isothermal transient ionic current technique was used in this study to characterise the instantaneous absorption properties (rate and capacity) of a few selected pharmaceutical excipients. The results indicate that the instantaneous and long term water absorption properties of pharmaceutical powders can differ considerably. The rate of instantaneous water absorption appears to correlate with the total surface area while the absorption capacity correlates more with the porosity of the powder.
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| 71. |
- Heidarian, Mina, et al.
(författare)
-
Influence of water-cellulose binding energy on stability of acetylsalicylic acid
- 2006
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 323:1-2, s. 139-145
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate how the energies of water binding in cellulose tabletting excipients influence the availability of moisture to induce hydrolysis of acetylsalisylic acid (ASA). Cellulose powders of varying degree of order, denoted as low-crystallinity cellulose (LCC) and high-crystallinity cellulose (HCC), were produced by treating ordinary microcrystalline cellulose (MCC) in ZnCl2 solutions of varying concentrations. Microcrystalline cellulose (MCC) and lactose monohydrate were used as reference excipients. The samples were then studied by X-ray diffraction, scanning electron microscopy, and differential scanning calorimetry (DSC). Different ratios of each excipient mixed with ASA were stored at 40% RH and 50 degrees C for 35 days to investigate the hydrolytic stability of the mixtures. Stability studies indicated that as concentration of HCC and MCC in binary mixtures with ASA was raised from 1 to 50% (w/w), ASA became increasingly unstable with respect to hydrolysis. Although LCC contained more moisture than the other celluloses, no such trend was observed in the LCC and lactose samples. DSC analysis revealed that each water molecule on the average was bound by more than three hydrogen bonds in the LCC and lactose structures and therefore remained predominantly unavailable to induce hydrolysis. The current study elucidates the necessity of evaluating the energy of water bindings in a pharmaceutical excipient when predicting the excipient's performance in mixtures comprising moisture-sensitive drugs.
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| 72. |
- Hellrup, Joel, et al.
(författare)
-
Pharmaceutical micro-particles give amorphous sucrose higher physical stability
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 409:1-2, s. 96-103
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore how pharmaceutical micro-sized filler particles affect the amorphous stability of sucrose in sucrose/filler particle composites produced by freeze-drying. Focus was put on the filler particles' properties crystallinity, hygroscopicity, hydrophobicity, and surface area, and their influence on physical stability of the amorphous phase. The micro-sized filler particles were examined with Blaine permeametry, gas adsorption, pycnometry, gravimetric vapour sorption, X-ray diffraction, and light microscopy before composites of sucrose and micro-sized filler particles were prepared by freeze-drying. The stability of the composites was examined with X-ray diffraction, differential scanning calorimetry (DSC), and microcalorimetry. All composites were amorphous and showed higher stability compared to pure amorphous sucrose, which was evident from a delay in heat and moisture-induced crystallization. However, calcium carbonate and oxazepam micro-sized filler particles lost their ability to stabilize the amorphous sucrose when exposed to humidity. The dry glass transition temperature (T-g) was higher for the composites, indicating the stabilization was mediated by a reduced molecular mobility of the amorphous phase.
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| 73. |
- Hellrup, Joel, et al.
(författare)
-
Powder compression mechanics of spray-dried lactose nanocomposites
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 518:1-2, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the structural impact of the nanofiller incorporation on the powder compression mechanics of spray-dried lactose. The lactose was co-spray-dried with three different nanofillers, that is, cellulose nanocrystals, sodium montmorillonite, and fumed silica, which led to lower micron sized nanocomposite particles with varying structure and morphology. The powder compression mechanics of the nanocomposites and physical mixtures of the neat spray-dried components were evaluated by a rational evaluation method with compression analysis as a tool using the Kawakita equation and the Shapiro-Konopicky-Heckel equation. Particle rearrangement dominated the initial compression profiles due to the small particle sizes of the materials. The strong contribution of particle rearrangement in the materials with fumed silica continued throughout the whole compression profile, which prohibited an in-depth material characterization. However, the lactose/cellulose nanocrystals and the lactose/sodium montmorillonite nanocomposites demonstrated increased yield pressure compared with the physical mixtures indicating increased particle hardness. This increase has likely to do with a reinforcement of the nanocomposite particles by skeleton formation of the nanoparticles. In summary, the rational evaluation applying compression analysis proved to be a valuable tool for mechanical evaluation for this type of materials unless they demonstrate particle rearrangement throughout the whole compression profile.
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| 74. |
- Hellrup, Joel, 1983-, et al.
(författare)
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Production and characterization of aluminium oxide nanoshells on spray dried lactose
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 529:1-2, s. 116-122
-
Tidskriftsartikel (refereegranskat)abstract
- Atomic layer deposition (ALD) enables deposition of dense nanometer thick metal oxide nanoshells on powder particles with precise thickness control. This leads to products with low weight fraction coating, also when depositing on nano- or micron sized powder particles. This study aimed at investigating the aluminium oxide nanoshell thickness required to prevent moisture sorption. The nanoshells were produced with ALD on spray-dried lactose, which is amorphous and extremely hygroscopic. The particles were studied with dynamic vapor sorption between 0 and 50% RH, light scattering, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and polarized light microscopy. The ALD did not induce any recrystallization of the amorphous lactose. The dynamic vapor sorption indicated that the moisture sorption was almost completely inhibited by the nanoshell. Neat amorphous lactose rapidly recrystallized upon moisture exposure. However, only ca. 15% of the amorphous lactose particles recrystallized of a sample with 9% (by weight) aluminium oxide nanoshell at storage for six months upon 75% RH/40 degrees C, which indicate that the moisture sorption was completely inhibited in the majority of the particles. In conclusion, the aluminium oxide nanoshells prevented moisture sorption and dramatically improved the long term physical stability of amorphous lactose. This shows the potential of the ALD-technique to protect drug microparticles.
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| 75. |
- Hens, Bart, et al.
(författare)
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Formulation predictive dissolution (fPD) testing to advance oral drug product development : An introduction to the US FDA funded '21st Century BA/BE' project
- 2018
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 548:1, s. 120-127
-
Forskningsöversikt (refereegranskat)abstract
- Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.
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| 76. |
- Herder, Jenny, 1975, et al.
(författare)
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Initial studies of water granulation of eight grades of hypromellose (HPMC)
- 2006
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 313:1-2, s. 57-65
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to investigate the water granulation mechanism of the hydrophilic matrix polymer HPMC in a high shear mixer and to relate the properties of the granules and tablets to the molecular weight and the degree of substitution for eight HPMC grades. Although the hydrophilic matrix system is a well known drug delivery one, there is a difficulty in that the desirable water granulation technique often causes problems in the presence of relatively large amounts of HPMC due to its hydrophilicity. The results of this study show that the properties of the granules and the tablets fall into two groups according to whether the molecular weight of the polymer is high or low. The granules of low molecular weight were smaller and more compact, with better flow properties but with less tensile strength of the compacts, whereas the opposite was valid for granules of high molecular weight. The explanation for these differences is linked to the proposed granulation mechanism of HPMC, in which the properties of the gel layer are important. The dominant factors governing the properties are the molecular weight and, to lesser extent, the degree of substitution.
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| 77. |
- Hyun, Sang-Min, et al.
(författare)
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Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate
- 2019
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 554, s. 61-71
-
Tidskriftsartikel (refereegranskat)abstract
- Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann’s triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7° ± 0.50° and 86.65° ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05° ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.
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| 78. |
- Höckerfelt, Mina Heidarian, et al.
(författare)
-
The crystallinity of cellulose controls the physical distribution of sorbed water and the capacity to present water for chemical degradation of a solid drug
- 2014
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 477:1-2, s. 326-333
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the research was to investigate the effect of moisture content of cellulose on the degradation of a drug in binary mixtures with cellulose. Physical mixtures of acetylsalicylic acid and two forms of cellulose, either microcrystalline cellulose or low crystalline cellulose, in the proportion 1:1 were stored at 50°C at a series of relative humidities (0-90%) for up to 175 days. The degradation rate constant of the drug increased with increased cellulose moisture content in a bi-regional fashion, with a low and a high degradation rate region. The shift from region 1 to 2 occurred at higher moisture content for the low crystalline cellulose. The relationships between rate constant and the temperature of maximum endothermic value overlapped for the two celluloses. It is proposed that the amount of water available for degradation of a solid drug is controlled by the water presenting capacity of cellulose which is dependent of the mechanism of sorption of water in cellulose. The water sorption of water can for cellulose satisfactorily be described by a two-site residence model with cellulose crystallinity as the structural correlate to the distribution between the two residence sites.
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| 79. |
- Ivanov, Alexander, et al.
(författare)
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Boronate-containing polymers form affinity complexes with mucin and enable tight and reversible occlusion of mucosal lumen by poly (vinyl alcohol) gel
- 2008
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 358:1-2, s. 36-43
-
Tidskriftsartikel (refereegranskat)abstract
- Copolymers of N-acryloyl-m-aminophenylboronic acid (NAAPBA) with N,N-dimethylarcrylamide (DMAA) formed insoluble interpolymer complexes with mucin from porcine stomach at pH 9.0. The complex formation based on boronate-sugar interactions took place between the similarly charged macromolecules and resulted in coacervate particles formation, which depended both on pH and ionic strength of the solution. the coacervation rate displayed a maximum at the intermediate DMAA_NAAPBA copolymer: mucin weight ratio, that is a pattern typical of interpolymer complex formation.
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| 80. |
- Johannesson, Jenny, et al.
(författare)
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3D-printing of solid lipid tablets from emulsion gels
- 2021
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 597
-
Tidskriftsartikel (refereegranskat)abstract
- Interest in 3D-printing technologies for pharmaceutical manufacturing of oral dosage forms is driven by the need for personalized medicines. Most research to date has focused on printing of polymeric-based drug delivery systems at high temperatures. Furthermore, oral formulation development is continuously challenged by the large number of poorly water-soluble drugs, which require more advanced enabling formulations to improve oral bioavailability. In this work, we used semi-solid extrusion (SSE) printing of emulsion gels with three types of emulsified lipid-based formulations (LBFs) to produce solid lipid tablets incorporating the poorly water-soluble drug, fenofibrate. Tablets were successfully 3D-printed from emulsion gels using SSE at room temperature, making the methodology particularly useful for thermolabile compounds. The tablets were well-defined in mass and disintegrated rapidly (<15 min). Importantly, the oil droplet size reconstituted after dispersion of the tablets and subsequent lipid digestion was similar to traditional liquid LBFs. This work demonstrates the successful use of SSE for fabricating solid lipid tablets based on emulsion gels. The method is further promising for on demand production of personalized dosage forms, necessary for flexible dosage adjustment in e.g., pediatric patients, when poorly water-soluble compounds constitute the core of the therapy.
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| 81. |
- Johannesson, Jenny, 1990-, et al.
(författare)
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Quality attributes for printable emulsion gels and 3D-printed tablets : Towards production of personalized dosage forms
- 2023
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 646
-
Tidskriftsartikel (refereegranskat)abstract
- 3D-printing technology offers a flexible manufacturing platform with the potential to address the need of personalized dosage forms. However, quality aspects of such small-scale, on-demand production of pharmaceutical products intended for personalization is still limited. The aim of this study was therefore to study critical quality control attributes of lipid tablets produced by semi-solid extrusion (SSE) 3D printing from emulsion gels incorporating a poorly water-soluble drug. Quality attributes for both the printable emulsion gel and the printed dosage forms were assessed. The emulsion gel was shown to be printable with accurate dosing for at least one month of storage at 4 degrees C. Tablets were 3D printed in different sizes and a correlation, R2 value of 0.99, was found between the weight and the drug content. The 3D-printed tablets complied with the mass and drug content uniformity requirements described in the European Pharmacopoeia.. Solid-state characterization of the tablets during short-term storage revealed no signs of crystallinity of the drug. Lastly, the lipid digestion and drug release were unchanged after short-term storage of the tablets. This study demonstrates the potential of SSE 3D printing for personalized dosing of a lipid-based formulation strategy and discusses central quality attributes for the printable formulation and the 3D-printed dosage form.
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| 82. |
- Jonsson, Henrik, 1987-, et al.
(författare)
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Crack nucleation and propagation in microcrystalline-cellulose based granules subject to uniaxial and triaxial load
- 2019
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 559, s. 130-137
-
Tidskriftsartikel (refereegranskat)abstract
- Cracking patterns in four kinds of granules, based on the common pharmaceutical excipient microcrystalline cellulose (MCC) and subject to compressive load, were examined. The initial pore structure and the location of initial failure under uniaxial compression were assessed using X-ray micro-computed tomography, whereas contact force development and onset of cracking under more complex compressive load were examined using a triaxial testing apparatus. Smoothed particle hydrodynamics (SPH) simulations were employed for numerical analysis of the stress distributions prior to cracking. For granules subject to uniaxial compression, initial cracking always occurred along the meridian and the precise location of the crack depended on the pore structure. Likewise, for granules subject to triaxial compression, the fracture plane of the primary crack was generally parallel to the dominant loading direction. The occurrence of cracking was highly dependent on the triaxiality ratio, i.e. the ratio between the punch displacements in the secondary and dominant loading directions. Compressive stresses in the lateral directions, induced by triaxial compression, prevented crack opening and fragmentation of the granule, something that could be verified by simulations. These results provide corroboration as well as further insights into previously observed differences between confined and unconfined compression of granular media.
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| 83. |
- Kaialy, Waseem, et al.
(författare)
-
Effect of carrier particle shape on dry powder inhaler performance
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 421:1, s. 12-23
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER = 1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER = 4.83 ± 0.18, ECM: ER = 5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a “limit” as increasing carrier ER from 4.83 ± 0.18 (ACM) to 5.89 ± 0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2 = 0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability.
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| 84. |
- Katta, Jyothi, et al.
(författare)
-
Spherical Crystallization of benzoic acid
- 2008
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 348:1-2, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with the development of a method for spherical crystallization of benzoic acid. Benzoic acid is dissolved in ethanol, water is used as anti-solvent and chloroform is used as bridging liquid. After an introductory screening of different methods, the influence of the amount of the bridging liquid, the solute concentration and the stirring rate is investigated. The product particle characterization includes the particle size distribution, morphology and strength. The mechanical strength of single agglomerates has been determined by compression in a materials testing machine, using a 10 N load cell. It is found that favourable properties are obtained if the bridging liquid is added during the crystallization. Larger and stronger well-shaped agglomerates are formed. The stress-strain curves are J-shaped with no clear fracturing of the particles, and are well correlated by an exponential-polynomial equation.
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| 85. |
- Kaunisto, Erik, et al.
(författare)
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Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.
- 2011
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 418, s. 54-77
-
Tidskriftsartikel (refereegranskat)abstract
- The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed.
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| 86. |
- Kazlauske, Jurgita, 1981, et al.
(författare)
-
Determination of the release mechanism of Theophylline from pellets coated with Surelease (R)-A water dispersion of ethyl cellulose
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 528:1-2, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease (R) and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease (R) films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 mm) of the coating layer controlling the drug release rate.
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| 87. |
- Kazlauske, Jurgita, 1981, et al.
(författare)
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The importance of the molecular weight of ethyl cellulose on the properties of aqueous-based controlled release coatings
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 519:1-2, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- Previous investigations of aqueous based ethyl cellulose (EC) latex dispersions have mainly focused on the commercially available viscosity grade 20 cps. In this study, dispersions of EC with varying viscosity grades (which correspond to molecular weights), ranging from 4 to 100 cps, were produced and characterised. The dispersions showed particle sizes around 200 nm and highly negative ζ-potentials (approx. −100 mV), which indicated stable dispersions as confirmed by sedimentation studies. The different latexes were used to produce free-standing film coatings. We hypothesised that the different viscosity grades of EC would result in different properties of the films. We found that an increase in viscosity grade (and higher molecular weight) resulted in lower coalescence between the particles during film formation and thus to higher water permeability than in film coatings of lower molecular weight. After exposure to water the EC 4 cps and 20 cps film coatings had a more porous structure in the side facing the air during production and drying after immersion in water. Molecular weight is therefore a factor that should be considered when producing pharmaceutical coatings for controlled release.
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| 88. |
- Knöös, Patrik, et al.
(författare)
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Quantifying the release of lactose from polymer matrix tablets with an amperometric biosensor utilizing cellobiose dehydrogenase.
- 2014
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 468:1-2, s. 121-132
-
Tidskriftsartikel (refereegranskat)abstract
- The release of lactose (hydrophilic) from polymer tablets made with hydrophobically modified poly(acrylic acid) (HMPAA) have been studied and compared it to the release of ibuprofen, a hydrophobic active substance. Lactose is one of the most used excipients for tablets, but lactose release has not been widely studied. One reason could be a lack of good analytical tools. A novel biosensor with cellobiose dehydrogenase (CDH) was used to detect the lactose release, which has a polydiallyldimethylammonium chloride (PDADMAC) layer that increases the response. A sample treatment using polyethylenimine (PEI) was developed to eliminate possible denaturants. The developed methodology provided a good approach to detect and quantify the released lactose. The release was studied with or without the presence of a model amphiphilic substance, sodium dodecyl sulphate (SDS), in the release medium. Ibuprofen showed very different release rates in the different media, which was attributed to hydrophobic interactions between the drug, the HMPAA and the SDS in the release medium. The release of hydrophilic lactose, which did not associate to any of the other components, was rapid and showed only minor differences. The new methodology provides a useful tool to further evaluate tablet formulations by a relatively simple set of experiments.
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| 89. |
- Larsson, Sylvia
(författare)
-
Understanding flow properties of mannitol powder at a range of temperature and humidity
- 2021
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 596
-
Tidskriftsartikel (refereegranskat)abstract
- Inadequate flowability of powders in industries during handling can cause many problems. For example, lack of flow from hoppers, poor tablet weight consistency, and low production rate in tableting. Many factors are known to commonly affect flow properties of powders, such as temperature, humidity and conditioning duration. In this paper, flow properties of a mannitol powder, which was conditioned between 24 and 72 h at various high relative humidities and temperature, were measured using a shear tester. A statistical model was developed to investigate the relative importance of these variables on the mannitol flow properties. The developed model showed all independent variables are significant in estimating bulk cohesion. Two separate approaches were used to evaluate inter-particle forces in the bulk, and how these changed with environmental conditions. First, inter-particle forces were inferred from the measured bulk properties using the Rumpf model approach. Secondly, inter-particle forces were predicted based on a model of moisture present on the particle surface using a combination of Kelvin model with the Laplace-Young (KLY) equation. The second approach also involved a new method to measure surface energy of mannitol powder based on measurements using Finite Dilution Inverse Gas Chromatography (FD-IGC). The surface energies of the mannitol powder were measured at high temperature (35 degrees C) and at different range of relative humidities. In spite of the fundamentally different approaches to the two ways of inferring inter-particles forces, these forces came out within less than 1.5:1 in magnitude. The Rumpf approach from bulk behaviour data obviously reflected the measured change in behaviour with humidity in particular, but this was not predicted from the KLY approach, however the likely reasons for this are postulated and recommendations for improvement are made.
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| 90. |
- Lindberg, Staffan, 1979-, et al.
(författare)
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PepFect15, a novel endosomolytic cell-penetrating peptide for oligonucleotide delivery via scavenger receptors
- 2012
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 441:1-2, s. 242-247
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Tidskriftsartikel (refereegranskat)abstract
- Gene-regulatory biomolecules such as splice-correcting oligonucleotides and anti-microRNA oligonucleotides are important tools in the struggle to understand and treat genetic disorders caused by defective gene expression or aberrant splicing. However, oligonucleotides generally suffer from low bioavailability, hence requiring efficient and non-toxic delivery vectors to reach their targets. Cell-penetrating peptides constitute a promising category of carrier molecules for intracellular delivery of bioactive cargo. In this study we present a novel cell-penetrating peptide, PepFect15, comprising the previously reported PepFect14 peptide modified with endosomolytic trifluoromethylquinoline moieties to facilitate endosomal escape. Pepfect15 efficiently delivers both splice-correcting oligonucleotides and anti-microRNA oligonucleotides into cells through a non-covalent complexation strategy. To our knowledge this is the first work that describes peptide-mediated anti-microRNA delivery. The peptide and its cargo form stable, negatively charged nanoparticles that are taken up by cells largely through scavenger receptor type A mediated endocytosis.
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| 91. |
- Ljusberg, Helena, et al.
(författare)
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Enzymatic characterization of lipid-based drug delivery systems
- 2005
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 298:2, s. 328-332
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Tidskriftsartikel (refereegranskat)abstract
- The present work introduces a simple and robust in vitro method for enzymatic characterisation of surface properties of lipid dispersions in aqueous media. The initial lipolysis rate in biorelevant media, using pancreatic lipase and a self-microemulsifying formulation (SMEDDS) containing digestible lipids as substrate, was determined. The impact of incorporating two sparingly water soluble model drugs, probucol and halofantrine, into the SMEDDS was studied. It was found that both model drugs reduced the initial rate of lipolysis compared with the vehicle, probucol having a larger effect than halofantrine. The reduction of initial lipolysis rate indicates that probucol and halofantrine are bound in the water/emulsion interface limiting the substrate availability.
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| 92. |
- Lobmann, Korbinian, et al.
(författare)
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Cellulose nanofibers as excipient for the delivery of poorly soluble drugs
- 2017
-
Ingår i: International Journal of Pharmaceutics. - : ELSEVIER SCIENCE BV. - 0378-5173 .- 1873-3476. ; 533:1, s. 285-297
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Tidskriftsartikel (refereegranskat)abstract
- Poor aqueous solubility of drugs is becoming an increasingly pronounced challenge in the formulation and development of drug delivery systems. To overcome the limitations associated with these problematic drugs, formulation scientists are required to use enabling strategies which often demands the use of new excipients. Cellulose nanofibers (CNFs) is such an excipient and it has only recently been described in the pharmaceutical field. In this review, the use of CNF in drug formulation with a focus on poorly soluble drugs is featured. In particular, the aim is to describe and discuss the many unique properties of CNFs, which make CNFs attractive as excipients in pharmaceutical sciences. Furthermore, the use of CNF as stabilizers for crystalline drug nanoparticles, as a matrix former to obtain a long-lasting sustained drug release over several weeks and as a film former with immediate release properties for poorly soluble drug are reported. Finally, the preparation of pharmaceutical CNF foams together with poorly soluble drugs is highlighted; foams, which offer a sustained drug delivery system with positive buoyancy.
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| 93. |
- Mahlin, Denny, et al.
(författare)
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A novel powder sample holder for the determination of glass transition temperatures by DMA
- 2009
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 371:1-2, s. 120-125
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Tidskriftsartikel (refereegranskat)abstract
- The use of a new sample holder for dynamic mechanical analysis (DMA) as a means to characterise the Tg of powdered hydroxypropyl methyl cellulose (HPMC) has been investigated. A sample holder was constructed consisting of a rectangular stainless steel container and a lid engineered to fit exactly within the walls of the container when clamped within a TA instruments Q800 DMA in dual cantilever configuration. Physical mixtures of HPMC (E4M) and aluminium oxide powders were placed in the holder and subjected to oscillating strains (1 Hz, 10 Hz and 100 Hz) whilst heated at 3 degrees C/min. The storage and loss modulus signals showed a large reduction in the mechanical strength above 150 degrees C which was attributed to a glass transition. Optimal experimental parameters were determined using a design of experiment procedure and by analysing the frequency dependence of Tg in Arrhenius plots. The parameters were a clamping pressure of 62 kPa, a mass ratio of 0.2 HPMC in aluminium oxide, and a loading mass of either 120 mg or 180 mg. At 1 Hz, a Tg of 177+/-1.2 degrees C (n=6) for powdered HPMC was obtained. In conclusion, the new powder holder was capable of measuring the Tg of pharmaceutical powders and a simple optimization protocol was established, useful in further applications of the DMA powder holder.
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| 94. |
- Mahlin, Denny, et al.
(författare)
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The influence of PVP incorporation on moisture-induced surface crystallization of amorphous spray-dried lactose particles
- 2006
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 321:1-2, s. 78-85
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that atomic force microscopy (AFM) may be an appropriate method for characterisation of the re-crystallization of amorphous particles. In this study, spray-dried composite particles consisting of lactose and polyvinyl pyrrolidon (PVP) were characterised by AFM and electron spectroscopy for chemical analysis (ESCA), and their response on increasing the relative humidity (RH) was investigated. The PVP content in the particles used was 0, 5 or 25 wt.% of either PVP K 17 or PVP K90. All composite particles were found to be enriched with PVP at the surface. The incorporation of PVP in the particles influenced the way the particles responded to an increase in RH. The specific RH interval in which the surface of the particles smoothened and the RH where crystallization could be detected, increased with an increase in the amount and molecular weight of the PVP in the particles. The crystallization kinetics of single particles was analysed with AFM and by utilising the JMAK equation. The rate constant for this transformation increased in an exponential manner with increasing RH. Furthermore, above the RH needed for the crystallization to occur, the exponential increase in the crystallization rate was larger for particles with higher polymer content which indicates that the stabilising effect decreases as the water content in the particles becomes higher. In this study we report a method for determination of crystallization kinetics on single composite particles, which is valuable when evaluating the effect of stabilisers in amorphous powders.
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| 95. |
- Mahmoodi, Foad, et al.
(författare)
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A comparison between two powder compaction parameters of plasticity : The effective medium A parameter and the Heckel 1/K parameter
- 2013
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 453:2, s. 295-299
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the research was to introduce a procedure to derive a powder compression parameter (EM A) representing particle yield stress using an effective medium equation and to compare the EM A parameter with the Heckel compression parameter (1/K). 16 pharmaceutical powders, including drugs and excipients, were compressed in a materials testing instrument and powder compression profiles were derived using the EM and Heckel equations. The compression profiles thus obtained could be sub-divided into regions among which one region was approximately linear and from this region, the compression parameters EM A and 1/K were calculated. A linear relationship between the EM A parameter and the 1/K parameter was obtained with a strong correlation. The slope of the plot was close to 1 (0.84) and the intercept of the plot was small in comparison to the range of parameter values obtained. The relationship between the theoretical EM A parameter and the 1/K parameter supports the interpretation of the empirical Heckel parameter as being a measure of yield stress. It is concluded that the combination of Heckel and EM equations represents a suitable procedure to derive a value of particle plasticity from powder compression data.
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| 96. |
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| 97. |
- Marku, Diana, et al.
(författare)
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Characterization of starch Pickering emulsions for potential applications in topical formulations.
- 2012
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 428:1-2, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work has been to characterize starch based Pickering emulsions as a first step to evaluate their possible use as vehicles for topical drug delivery. A minor phase study of emulsions with high oil content has been performed. Emulsion stability against coalescence over eight weeks and after mild centrifugation treatment has been studied. The particle size, rheological properties and in vitro skin penetration of emulsions containing three different oils (Miglyol, paraffin and sheanut oil) was investigated. It was shown that it is possible to produce oil in water starched stabilised Pickering emulsions with oil content as high as 56%. Furthermore, this emulsions show good stability during storage over eight weeks and towards mild centrifugation. The particle size of the systems are only dependent on the ratio between oil and starch and for liquid oils the type of oil do not affect the particle size. The type of oil also affects the cosmetic and rheological properties of the creams but did not affect the transdermal diffusion in in vitro tests. However, it seems as if the Pickering emulsions affected the transport over the skin, as the flux was twice that of what has been previously reported for solutions.
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| 98. |
- Martins, Murillo L, et al.
(författare)
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Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 524:1-2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Since potential changes in the dynamics and mobility of drugs upon complexation for delivery may affect their ultimate efficacy, we have investigated the dynamics of two local anesthetic molecules, bupivacaine (BVC, C18H28N2O) and ropivacaine (RVC, C17H26N2O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The study was carried out by neutron scattering spectroscopy, along with thermal analysis, and density functional theory computation. Mean square displacements suggest that RVC may be less flexible in crystalline form than BVC, but both molecules exhibit very similar dynamics when confined in HP-β-CD. The use of vibrational analysis by density functional theory (DFT) made possible the identification of molecular modes that are most affected in both molecules by insertion into HP-β-CD, namely those of the piperidine rings and methyl groups. Nonetheless, the somewhat greater structure in the vibrational spectrum at room temperature of complexed RVC than that of BVC, suggests that the effects of complexation are more severe for the latter. This unique approach to the molecular level study of encapsulated drugs should lead to deeper understanding of their mobility and the respective release dynamics.
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| 99. |
- Marucci, Mariagrazia, et al.
(författare)
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Evaluation of osmotic effects on coated pellets using a mechanistic model
- 2007
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 336:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a simple experimental methodology and to develop a mechanistic model to characterize the release mechanism from pellets developing cracks during the release process with special focus on osmotic effects. The release of remoxipride from pellets coated with an ethyl cellulose film was chosen as a case study. Dose release experiments at different bulk osmotic pressures revealed that the release process was mainly osmotically driven. The model was used to calculate the solvent permeability of the coating, 1.1 x 10(-10) m(2) h(-1) MPa-1 The model was validated by release experiments using similar pellets having different coating thicknesses. The effective diffusion coefficient of remoxipride in the coating was also calculated and found to be 1.7 x 10(-1) m(2) h(-1). A series of experiments was performed in which the osmotic pressure of the receiving solution was changed during the experiment. From the results of these experiments, the area of the cracks in the film, formed by the hydrostatic pressure built up inside the pellets, was estimated to be 3.5 x 10(-5) m(2)/m(2) coating. It could also be deduced that the solvent permeability of the coating film was affected by swelling in the same way at different osmotic pressures. (C) 2006 Elsevier B.V. All rights reserved.
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| 100. |
- Marucci, Mariagrazia, et al.
(författare)
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New insights on how to adjust the release profile from coated pellets by varying the molecular weight of ethyl cellulose in the coating film
- 2013
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 458:1, s. 218-223
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Tidskriftsartikel (refereegranskat)abstract
- The major aims of this work were to study the effect of the molecular weight (Mw) of ethyl cellulose (EC) on the drug release profile from metoprolol succinate pellets coated with films comprising EC and hydroxypropyl cellulose (HPC) with a weight ratio of 70:30, and to understand the mechanisms behind the different release profiles. A broad range of Mws was used, and the kinetics of drug release and HPC leaching followed. The higher the Mw of EC, the slower the HPC leaching and the drug release processes. Drug release occurred by diffusion through the pores created in the coating by the HPC leaching. A novel method was used to explain the differences in the release profiles: the effective diffusion coefficient (De) of the drug in the coating film was determined using a mechanistic model and compared to the amount of HPC leached. A linear dependence was found between De and the amount of HPC leached and, importantly, the value of the proportionality constant decreased with increasing Mw of EC. This suggests that the Mw of EC affects the drug release profile by affecting the phase separated microstructure of the coating and the hindrance it imparts to drug diffusion.
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