| 1. |
- Bengtsson, Jörgen, et al.
(författare)
-
The use of a deuterated calibrator for in vivo recovery estimations in microdialysis studies
- 2008
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:8, s. 3433-3441
-
Tidskriftsartikel (refereegranskat)abstract
- One of the crucial issues in quantitative microdialysis is the reliability of recovery estimates to correctly estimate unbound drug tissue concentrations. If a deuterated calibrator is used for retrodialysis, the calibrator has the same properties as the study drug. However, recovery of the calibrator may be affected by the presence of the drug in the tissues. The aim of this study was to investigate the recovery of deuterated morphine with time in the absence and presence of morphine in rat tissues. Microdialysis probes were placed in the brain and blood of eight rats. Ringer's solution containing D3-morphine was perfused throughout the study and recovery was estimated. After a stabilization period of 3 h, an exponential infusion of morphine was administered over 4 h. The presence of morphine did not affect the recovery of D3-morphine from brain or blood. The average recovery values (SD) were 0.145 (0.039) and 0.131 (0.048) during the stabilization and infusion periods, respectively, for the brain probe and 0.792 (0.055) and 0.790 (0.084), respectively, for the blood probe. The recovery of deuterated morphine was stable over time in the brain and in blood, and was not affected by the presence of pharmacologically concentrations of morphine.
|
|
| 2. |
- Bergstrom, P. O., et al.
(författare)
-
Crystal structure and physical properties of two polymorphs of ropivacaine HCl
- 2006
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:3, s. 680-688
-
Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of two polymorphs of ropivacaine HCl have been determined, as well as their relative stability up to 100 degrees C. A geometric restriction for a solid-state transition between the two polymorphs has been identified. The packing density along the H-bonded chains form the basis for a model explaining the kinetic crystallization of the metastable form. The difference in stability and physicochemical properties between the two polymorphs can be attributed to the difference in crystal structure.
|
|
| 3. |
|
|
| 4. |
- Boström, Emma, et al.
(författare)
-
Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833
- 2005
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 94:5, s. 1060-1066
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood-brain barrier (BBB) with concomitantly administered P-gp substrates.
|
|
| 5. |
|
|
| 6. |
- Brohede, Ulrika, et al.
(författare)
-
Characterization of the drug release process by investigation of its temperature dependence
- 2004
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:7, s. 1796-1803
-
Tidskriftsartikel (refereegranskat)abstract
- Temperature-dependent drug release from disintegrating tablets made of NaCl-containing agglomerated micronized cellulose (AMC) granules has been studied to characterize the release process. Release measurements on tablets compacted at three different compaction pressures; 50, 100, and 200 MPa, were performed at seven different temperatures; 6, 23, 33, 43, 50, 55, and 63°C using the recently developed alternating ionic current method. Tablets compacted at different compaction pressures showed similar release rates. The release process was found to be diffusion-controlled, and the activation energy of the diffusion coefficient was comparable to that obtained for diffusion in pure water. The results show that the AMC granules in contact with water swell to a size and shape that is only slightly affected by their compaction history and the ion diffusion operates mainly within liquid-filled pores within the AMC granules. By using the temperature dependence of the release process, it was possible to reach this conclusion without any assumptions concerning the number and radii of the granules into which the tablets disintegrated. Further, the magnitude of the effective diffusion coefficient was found to be ∼7.5 · 10−10 cm2/s, which is ∼four orders of magnitude lower than for unhindered diffusion of Na+ and Cl− in water but similar to the diffusion coefficient for protons and OH− ions in microcrystalline cellulose.
|
|
| 7. |
- Brohede, Ulrika, et al.
(författare)
-
Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:11, s. 3087-3099
-
Tidskriftsartikel (refereegranskat)abstract
- Release of NaCl in both the axial and radial directions from cylindrical ethyl cellulose tablets were investigated by the alternating ionic current method. The pore structure of the investigated binary mixtures was examined by mercury porosimetry and scanning electron microscopy, and the nm range fractal surface dimension of tablet pore walls was extracted from krypton gas adsorption isotherms. The drug release was shown to consist of two overlapping processes of which the first was ascribed to dissolution of NaCl close to the tablet boundary followed by subsequent diffusion through a thin ethyl cellulose layer and a second from which a porosity percolation threshold of 0.22 could be extracted. As well, a cross-over to effective-medium behaviour at a porosity of 0.44 was observed. The presented findings showed that drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces. Thus, the present study brings forward knowledge important for the tailoring of controlled drug delivery vehicles with optimum release patterns.
|
|
| 8. |
|
|
| 9. |
- Elfstrand, Lidia, et al.
(författare)
-
The effect of starch material, encapsulated protein and production conditions on the protein release from starch microspheres.
- 2009
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549. ; 98, s. 3802-3815
-
Tidskriftsartikel (refereegranskat)abstract
- The present study describes the preparation of 11 batches of starch microspheres for drug delivery. Parameters such as the type of starch material, the type of protein, and the incubation time of the process were varied, and the obtained microspheres differed in yield, encapsulation efficiency and physical properties. The crystalline/ordered structure (obtained through X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC)), the microscopic appearance and the surface morphology (viewed with scanning electron microscopy (SEM)) were found to differ between the batches depending on the starch type, encapsulated protein and incubation conditions that were employed. Freeze-drying was found to have a destructive effect on the ordered structure of the starch and this effect varied with regard to preparation conditions. Drug release experiments demonstrated that the release from the starch matrix depended on the type of protein as well as on the incubation time during the manufacturing at temperatures of 6 degrees C and 37 degrees C. The enzymatic degradation of starch was slightly different between the materials depending on the crystalline/ordered structure that had formed during the preparation. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
|
|
| 10. |
- Elversson, Jessica, et al.
(författare)
-
An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:4, s. 905-912
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate an atomic force microscopy (A-FM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either ""solid"" or ""hollow."" A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm(3) corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the 3 average effective particle density was 0.95 g/cm, indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.
|
|
| 11. |
- Elversson, J, et al.
(författare)
-
Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying
- 2003
-
Ingår i: Journal of Pharmaceutical Sciences. - : Wiley. - 0022-3549 .- 1520-6017. ; 92, s. 900-910
-
Tidskriftsartikel (refereegranskat)abstract
- To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration
|
|
| 12. |
- Elversson, Jessica, et al.
(författare)
-
Particle size and density in spray drying : effects of carbohydrate properties
- 2005
-
Ingår i: Journal of Pharmaceutical Sciences. - : Wiley. - 0022-3549 .- 1520-6017. ; 94:9, s. 2049-2060
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol, and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e., scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and light microscopy), differential scanning calorimetry (DSC), gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density, measured by gas pycnometry, was found negatively correlated to the feed concentration. Due to the nonlinear relationship between the feed concentration and the particle size, it was concluded that higher solids load would cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles.
|
|
| 13. |
- Elversson, J, et al.
(författare)
-
Particle size and density in spray drying - effects of carbohydrate properties
- 2005
-
Ingår i: Journal of Pharmaceutical Sciences. - 0022-3549 .- 1520-6017. ; 94, s. 2049-2060
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e. scanning electron microscopy, confocal laser scanning microscopy and light microscopy), differential scanning calorimetry, gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density was found negatively correlated to the feed concentration. Due to the non-linear relationship between the feed concentration and the particle size, it was concluded that higher solids load may cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles
|
|
| 14. |
|
|
| 15. |
- Fransén, Nelly, et al.
(författare)
-
Changes in the mucoadhesion of powder formulations after drug application investigated with a simplified method
- 2008
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:9, s. 3855-3864
-
Tidskriftsartikel (refereegranskat)abstract
- The residence time in the nasal cavity can be prolonged by dry particles that absorb water and subsequently increase the viscosity of the mucus layer. A novel nasal drug delivery system based on interactive mixtures has previously been developed, where fine particles of the active component are adhered to the surface of mucoadhesive carrier particles by dry mixing. The surface coverage may alter the original mucoadhesiveness of the carrier particles and to investigate this, a simplified tensile strength method was developed and evaluated. Reliable results were obtained with a plastic coated absorbent paper covered by a mucin solution as a substitution for porcine nasal mucosa and should also be applicable to other dry particle systems. The method showed that the swelling of sodium starch glycolate particles was slightly delayed, corresponding to the degree of hydrophobic surface coverage. Carrier particles of partly pregelatinized maize starch were not influenced by the addition of a hydrophobic substance, probably because of the rough particle shape that inhibited a complete surface coverage. It was concluded that the surface coverage of carrier particles in interactive mixtures only could cause a short delay in water absorption that should not affect their mucoadhesive characteristics in vivo.
|
|
| 16. |
- Frenning, Göran, et al.
(författare)
-
A new method for characterizing the release of drugs from tablets in low liquid surroundings
- 2002
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 91:3, s. 776-784
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to introduce a method capable of determining early drug dissolution in small amounts of liquid. The method is based on the measurement of the alternating ionic current through a cell containing the dissolution medium and the substance to be dissolved. Both the initial and more prolonged absorption of liquid into tablets can also be determined by using the same technique. The method has been tested on two tablet formulations containing agglomerated micronized cellulose and NaCl as a model drug. Release of NaCl was delayed from both formulations; the extent of the delay was strongly formulation-dependent only when the surrounding liquid was in short supply. This finding shows that new drug dissolution phenomena may be encountered in small liquid volumes; these phenomena would not have been seen with the large volume methods normally used in in vitro dissolution tests. Hence, for formulations intended for sublingual, buccal, or rectal administration, i.e., in areas where liquid is scarce, in vitro dissolution tests should be performed in small volumes of dissolution medium.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Hägerström, Helene, et al.
(författare)
-
Low-frequency dielectric spectroscopy as a tool for studying the compatibility between pharmaceutical gels and mucous tissue
- 2003
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 92:9, s. 1869-1881
-
Tidskriftsartikel (refereegranskat)abstract
- This interdisciplinary work demonstrates how low-frequency dielectric spectroscopy, a technique that is frequently used within physics, can be used to assess the possibilities of intimate surface contact between a polymer gel and mucous tissue, which is generally considered to be the first step in the mucoadhesion process. The dielectric responses of five different gels, of freshly excised porcine nasal mucosa and of systems made by combining the two were measured. All spectra were modeled by a Randles electric circuit containing a diffusion element, a barrier resistance in parallel with a capacitance, and a high-frequency resistance. The results were used to create a measure of the compatibility between the gel and the mucus, which we have named the compatibility factor. Thus, the compatibility factor provides us with a measure of the ease with which a charged species passes the interface between a gel and the mucus layer. The compatibility factor is calculated from the high frequency (kHz region) response of the gel, of the mucosa, and of the combined system. The two highest compatibility factors in this study were obtained for gels based on crosslinked poly(acrylic acid) and chitosan, which was in agreement with the results from mucoadhesion measurements that were performed using a tensile strength method.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Körner, Anna, et al.
(författare)
-
Tuning the polymer release from hydrophilic matrix tablets by mixing short and long matrix polymers
- 2005
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 1520-6017 .- 0022-3549. ; 94:4, s. 759-769
-
Tidskriftsartikel (refereegranskat)abstract
- In this work a rotating disc method was developed for studying the dissolution process of bimodal polymer tablets, whose dissolution rates have been tuned by mixing low-molecular weight and high-molecular weight samples of poly(ethylene oxide) in various proportions. The tablets were prepared along different routes, by mixing the polymer fractions as powders or by mixing on a molecular level so that the effect of tablet heterogeneity could be assessed, but also by purifying the original powders so the effect of additives could be determined. When the mixed tablet was dominated by the low-molecular weight fraction, a faster dissolution was observed for the tablet mixed at the powder level. In those cases small gel pieces were released from the tablet during the whole dissolution process. As long as no gel piece erosion was observed, it did not matter if the two polymer fractions were blended on the molecular level or on the powder level, the steady-state dissolution rate was the same. The presence of small amounts of additives in the nonpurified commercial samples had no significant effect on the tablet dissolution within the uncertainty of the experiment.
|
|
| 26. |
- Lafitte, Géraldine, et al.
(författare)
-
Diffusion of nutrients molecules and model drug carriers through mucin layer investigated by magnetic resonance imaging with chemical shift resolution
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549. ; 96:2, s. 258-263
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance imaging (MRI) with chemical shift resolution is a recent extension of MRI and it provides information about species resolved molecular transport on the macroscopic scale in complex systems. In this contribution, we show that by using this novel method, one can predict the behavior of drug and food molecules when they are in contact with the mucosal layer in the gastrointestinal tract. For the first time, the transport properties of a mixture of nutrients (i.e., a solution of ethanol and glucose) and of a model drug carrier (i.e., an equimolar solution of cationic and nonionic surfactants) through a mucin gel have been investigated. This study shows that transport properties of the diffusing molecules through a mucin gel are dependent on their size and physicochemical properties. In addition, we show that mucin gel acts as an efficient selective barrier. It favors the disintegration of mixed micelles of nonionic and cationic surfactants by stopping the diffusion of cationic surfactants with slightly affecting the diffusion of the nonionic surfactants. (c) 2006 Wiley-Liss, Inc.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Nielsen, Flemming S., et al.
(författare)
-
Characterization of prototype self-nanoemulsifying formulations of lipophilic compounds
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549. ; 96:4, s. 876-892
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes the evaluation and characterization of a self-nanoemulsifying drug delivery system (SNEDDS) consisting of a nonionic surfactant (Cremophor RH40), a mixture of long chain mono-, di-, and triacylglycerides (Maisine 35-1 and Sesame oil) and ethanol. Compositions containing 10% (w/w) ethanol, 40%-60% (w/w) lipid content, and 30%-50% (w/w) Cremophor RH40 were identified as pharmaceutically relevant, robust, and self-nanoemulsifying when dispersed in aqueous media. The influence of adding three different lipophilic model drug compounds (danazol, halofantrine, and probucol) to the SNEDDS was evaluated. While danazol precipitated from the SNEDDS after dispersion in aqueous media, halofantrine and procubol remained solubilized. Halofantrine- and procubol-loaded SNEDDS were evaluated in both saline and in media simulating fasted and fed-state intestinal fluid (FaSSIF and FeSSIF) using dynamic light scattering and small-angle X-ray scattering (SAXS) techniques. Stable nanoemulsions with droplet sizes in the range of 20-50 nm were formed in all media and with and without drugs. The mean size of the droplets was neither affected significantly by being dispersed into the media simulating gastro intestinal fluid, nor by addition of the drug.
|
|
| 30. |
- Nordström, Fredrik, et al.
(författare)
-
Analysis of solution nonideality of a pseudomorphic drug system through a comprehensive thermodynamic framework for the design of a crystallization process
- 2004
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:4, s. 995-1004
-
Tidskriftsartikel (refereegranskat)abstract
- Solutions of a semipolar drug belonging to the alpha(v) beta(iii) integrin antagonist class of compounds were studied in a comprehensive thermodynamic framework. The solubility of two pseudomorphic forms (an anhydrate and a monohydrate) was measured at several temperatures and various solvent mixtures of acetonitrile and water. Both forms displayed a bell-shaped solubility behavior as a function of cosolvent composition. Thermodynamic framework used to analyze the data comprised van't Hoff and enthalpy-entropy compensation analyses. The two pseudomorphs exhibited linear temperature dependence from 25 to 65degreesC at all solvent compositions (i.e., ideal behavior with temperature for fixed solvent composition). Plots of enthalpy of solublization and Gibbs free energy showed two distinct regions with contrasting thermodynamic, and consequently, underlying structural properties (indicating non-deal behavior with solvent composition for a fixed temperature). Solubility increased due to entropy effects in the acetonitrile rich region, whereas enthalpy effects dominated solublization in the water-rich region. Quantification of this phenomenon by plotting DeltaH versus DeltaG showed considerable nonlinearity, and that the two regions were separated by a significant discontinuity-a trend rarely seen before in the literature. The reason behind this behavior is believed to be due to the complex interactions in the solution of the drug in water acetonitrile solvent system. A very significant aspect of the comprehensive thermodynamic analysis is that it helped explain the puzzling feature of the data, which showed that the free energy of phase transformation between the two pseudomorphic forms for a given temperature was not independent of the solvent composition. The resulting explanation has major consequences for crystallization process development.
|
|
| 31. |
- Nordström, Fredrik, et al.
(författare)
-
Phase Equilibria and Thermodynamics of p-Hydroxybenzoic acid
- 2006
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:4, s. 748-760
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalence of phases and associated solubilities of p-hydroxybenzoic acid have been investigated in methanol, acetonitrile, acetic acid, acetone, water, and ethyl acetate at temperatures from 10 to 50 degrees C. Thermodynamic data was acquired through determination of van't Hoff enthalpy of solution, enthalpy of fusion, and melting temperature. Indications of polymorphic enantiotropy were found primarily through solubility analysis and FTIR-ATR. A comprehensive thermodynamic investigation disclosed correlation between the van't Hoff enthalpy of solution and the solubility in different solvents. A higher solubility is linked to a lower van't Hoff enthalpy of solution. A thermodynamic analysis to discriminate between different solid phases is presented.
|
|
| 32. |
- Nordström, Josefina, et al.
(författare)
-
A particle rearrangement index based on the Kawakita powder compression equation
- 2009
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 98:3, s. 1053-1063
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, the effect of original particle size on the Kawakita parameters, denoted a and b, has been studied using four model materials of different compression mechanics. It was found that fine powders, possibly showing significant particle rearrangement at low compression pressures, showed low values of parameter b(-1) and high values of parameter a. It is thus proposed that the product of these parameters is an indication of the overall contribution of particle rearrangement to the compression profile. Above a critical original particle size of a powder, particle rearrangement is negligible for the overall compression profile and below this critical particle size, particle rearrangement becomes significant. A critical particle size of about 40 microm was obtained. A classification of powders into groups dependent on the incidence of particle rearrangement is discussed and it is suggested that a rearrangement index and a classification system could be used as tools to enable rational interpretations of global compression parameters.
|
|
| 33. |
- Nordström, Josefina, et al.
(författare)
-
On the role of granule yield strength for the compactibility of granular solids
- 2008
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:11, s. 4807-4814
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this article was to explore the relationship between mechanical properties of single granules and the evolution in tensile strength and tablet micro-structure. Granules of different expected deformation behavior were used as model materials. It is suggested that the role of plasticity in this context is twofold: firstly, to affect the rate of compactibility and thus the pressure range needed to reach the maximal attained tablet strength and, secondly, to affect the mode of deformation of the granules and thus the maximal attained tablet strength. A decrease in yield pressure of single granules increased the tablet tensile strength at a given compaction pressure. The yield pressure can be controlled by the granule composition and porosity.
|
|
| 34. |
- Paulsson, Mattias, et al.
(författare)
-
Controlled drug release from gels using surfactant aggregates : I. Effect of lipophilic interactions for a series of uncharged substances
- 2001
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 90:9, s. 1216-1225
-
Tidskriftsartikel (refereegranskat)abstract
- Gels are often used for the delivery of drugs because they have rheological properties that will give a long residence time. Most pharmaceutical gels consist of approximately 99% water and a polymer matrix that will not hinder the release of drugs with a small molecular weight. To fully take advantage of the residence time, it is necessary to have a sustained drug release. In this paper it is suggested that surfactant micelles can be used to control the release from gels. The in vitro release under physiological conditions of five parabens from four different poly(acrylic acid) gels (Carbopol 934, 940, 1342) and one gellan gum (Gelrite) gel was measured using a USP dissolution bath modified for gels, and the diffusion coefficients were calculated. The diffusion coefficient of uncharged parabens was generally lower in gels with lipophilic modifications, such as C1342, and the greatest effect was seen for butylparaben, with a diffusion that was 25% lower than that in C934 (lacking lipophilic modification). Addition of surfactant micelles to gels delayed the release of all the uncharged drugs in all types of gels studied. The slowest release was seen for butylparaben in a lipophilically modified gel with micelles present. The diffusion coefficient in such a system was almost 30 times smaller than that in C934 without micelles.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Stålberg, Olle, et al.
(författare)
-
Structure-interaction relationships between the bile acid GCA and pharmaceuticals using multivariate data analysis and capillary electrophoresis
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:8, s. 2057-2073
-
Tidskriftsartikel (refereegranskat)abstract
- Capillary electrophoresis (CE) has been used in an interaction study of 66 pharmaceutical compounds with the bile acid glycocholate (GCA). The developed method proved to have a high precision in its ability to determine the mobility of drugs in buffer and buffer bile acids solutions. The relationship between solute structure and interaction with GCA was studied using two-dimensional descriptors with the in-house software SELMA and a three-dimensional model (quantum mechanical descriptors) in combination with the experimental CE-interaction data. The multivariate analysis method used was projection to latent structures by means of partial least squares (PLS). Two selections of training and test set were used for evaluation of a two-class model on interaction data. In the first selection all observations were used for training set, for example, creating a model, and re-predicting the observations on the model. A successful prediction on 85% of the drugs was observed using this model. The second selection used the 21 first tested compounds in the training set, where 78% of the compounds were correctly predicted using the two-dimensional model (SELMA) on the remaining 45 compounds and, respectively, 82% using the three-dimensional (quantum mechanical) model. Analysis of the impact of the descriptors showed that descriptors relating to hydrophobicity have a large positive effect on the interaction. Descriptors relating to polar properties have a pronounced negative effect on the interaction of drugs with bile acids.
|
|
| 39. |
- Svärd, Michael, et al.
(författare)
-
Oiling out or molten hydrate-liquid-liquid phase separation in the system vanillin-water
- 2007
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:9, s. 2390-2398
-
Tidskriftsartikel (refereegranskat)abstract
- Vanillin crystals in a saturated aqueous solution disappear and a second liquid phase emerges when the temperature is raised above 51 degrees C. The phenomenon has been investigated with crystallization and equilibration experiments, using DSC, TGA, XRD and hot-stage microscopy for analysis. The new liquid solidifies on cooling, appears to melt at 51 degrees C, and has a composition corresponding to a dihydrate. However, no solid hydrate can be detected by XRD, and it is shown that the true explanation is that a liquid-liquid phase separation occurs above 51 degrees C where the vanillin-rich phase has a composition close to a dihydrate. To our knowledge, liquid-liquid phase separation has not previously been reported for the system vanillin-water, even though thousands of tonnes of vanillin are produced globally every year.
|
|
| 40. |
- Syvänen, Stina, et al.
(författare)
-
Pharmacokinetics of P-glycoprotein inhibition in the rat blood-brain barrier
- 2008
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:12, s. 5386-5400
-
Tidskriftsartikel (refereegranskat)abstract
- This article describes the experimental set-up and pharmacokinetic modeling of P-glycoprotein function in the rat blood-brain barrier using [(11)C]verapamil as the substrate and cyclosporin A as an inhibitor of P-gp. [(11)C]verapamil was administered to rats as an i.v. bolus dose followed by graded infusions to obtain steady-state concentrations in the brain during 70 min. CsA was administered as a bolus followed by a constant infusion 20 min after the start of the [(11)C]verapamil infusion. The brain uptake of [(11)C]verapamil over 2 h was portrayed in a sequence of PET scans in parallel with measurement of [(11)C]verapamil concentrations in blood and plasma and CsA concentrations in blood. Mixed effects modeling in NONMEM was used to build a pharmacokinetic model of CsA-induced P-gp inhibition. The brain pharmacokinetics of [(11)C]verapamil was well described by a two-compartment model. The effect of CsA on the uptake of [(11)C]verapamil in the brain was best described by an inhibitory indirect effect model with an effect on the transport of [(11)C]verapamil out of the brain. The CsA concentration required to obtain 50% of the maximal inhibition was 4.9 microg/mL (4.1 microM). The model parameters indicated that 93% of the outward transport of [(11)C]verapamil was P-gp mediated.
|
|
| 41. |
- Toropainen, Tarja, et al.
(författare)
-
Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method
- 2006
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:10, s. 2235-2245
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 C) the yield of the powder was 65 +/- 12% with 0.14 +/- 0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93 +/- 2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41 +/- 10%) and SEDS-processed budesonide without CD (61 +/- 3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.
|
|
| 42. |
- Tärning, Joel, 1977, et al.
(författare)
-
Pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat.
- 2008
-
Ingår i: Journal of pharmaceutical sciences. - : Elsevier BV. - 1520-6017 .- 0022-3549. ; 97:8, s. 3400-10
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the pharmacokinetic properties of piperaquine in the rat after intravenous and oral administration, and to identify and characterize the main piperaquine metabolites in rat plasma, urine, faeces and bile after intravenous administration. Male Sprague-Dawley rats were administered piperaquine as an emulsion orally or as a short-term intravenous infusion. Venous blood for pharmacokinetic evaluation was frequently withdrawn up to 90 h after dose. Urine, bile and faeces were collected after an infusion in rats kept in metabolic cages or in anesthetized rats. Pharmacokinetic characterization was done by compartmental modeling and non-compartmental analysis using WinNonlin. Piperaquine disposition was best described by a 3-compartment model with a rapid initial distribution phase after intravenous administration. The pharmacokinetics of piperaquine was characterized by a low clearance, a large volume of distribution and a long terminal half-life. Piperaquine displayed a low biliary clearance and less than 1% of the total dose was recovered in urine. The absolute oral bioavailability was approximately 50%. The main metabolite after intravenous administration of piperaquine was a carboxylic acid product identical to that reported in humans. The similarity with results in humans indicates the rat to be a suitable species for nonclinical in vivo piperaquine studies.
|
|
| 43. |
- Welch, Ken, et al.
(författare)
-
Simultaneous Measurement of Drug Release and Liquid Uptake in Pharmaceutical Tablets
- 2003
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 92:6, s. 1242-1249
-
Tidskriftsartikel (refereegranskat)abstract
- A new method is introduced that allows drug release and liquid absorption to be studied simultaneously. The drug release is measured by the alternating ionic current (AIC) method, and the study of liquid uptake is accomplished with a sensitive microbalance from a processor tensiometer. We show that the method can be employed to study anomalous diffusion in the initial phase of the drug release process of disintegrating systems. We also demonstrate that the diffusion layer thickness and the diffusion coefficient in a dissolving system can be obtained with the new measurement technique.
|
|
| 44. |
- Welin-Berger, K., et al.
(författare)
-
In vitro-in vivo correlation in man of a topically applied local anesthetic agent using numerical convolution and deconvolution
- 2003
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476 .- 0022-3549. ; 92:2, s. 398-406
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the relevance of the in vitro permeation method used at our laboratory in predicting in vivo dermal and transdermal absorption. Two different emulsions, a submicron oil-in-water (o/w) emulsion and a semisolid water-in-oil (w/o) emulsion, containing a model compound were investigated. The in vitro permeation rate of the compound from these emulsions was measured using static diffusion cells with human skin as membrane. The emulsions were allowed to remain in contact with the skin in the donor chamber for 15, 60, and 240 min. The study was monitored for 240 min and the steady state flux was calculated. The systemic concentration of the compound was measured in vivo as a function of time after dermal application to healthy volunteers with 15 and 60 min of application. A short-lasting i.v. infusion study in healthy volunteers was used to simulate the i.v. bolus dose. Numerical convolution was used to predict the in vivo plasma concentration of the compound while the in vivo absorption rate of the compound was estimated using numerical deconvolution. To establish correlation, the predicted in vivo flux was compared with the corresponding observed in vitro parameter after adjusting for the lag time. No major differences were seen in the systemic plasma levels between the two emulsions, which is in close agreement with the steady state flux measured in vitro. A linear correlation representing a point-to-point relationship was established for each of the investigated formulations and application times. The longer application time was predicted more accurately for both emulsions.
|
|
| 45. |
- Reusch, T B H, et al.
(författare)
-
Inter- and intralocus recombination drive MHC class IIB gene diversification in a teleost, the three-spined stickleback Gasterosteus aculeatus
- 2005
-
Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 61:4, s. 45-531
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The mutational mechanism underlying the striking diversity in MHC (major histocompatibility complex) genes in vertebrates is still controversial. In order to evaluate the role of inter- and intragenic recombination in MHC gene diversification, we examined patterns of nucleotide polymorphism across an exon/intron boundary in a sample of 31 MHC class IIB sequences of three-spined stickleback (Gasterosteus aculeatus). MHC class IIB genes of G. aculeatus were previously shown to be under diversifying (positive) selection in mate choice and pathogen selection experiments. Based on recoding of alignment gaps, complete intron 2 sequences were grouped into three clusters using maximum-parsimony analysis. Two of these groups had > 90% bootstrap support and were tentatively assigned single locus status. Intron nucleotide diversity within and among loci was low (p-distance within and among groups = 0.016 and 0.019, respectively) and fourfold lower than the rate of silent mutations in exon 2, suggesting that noncoding regions are homogenized by frequent interlocus recombination. A substitution analysis using GENECONV revealed as many intergenic conversion events as intragenic ones. Recombination between loci may explain the occurrence of sequence variants that are particularly divergent, as is the case in three-spined stickleback, with nucleotide diversity attaining d(N) = 0.39 (peptide-binding residues only). For both MHC class II loci we also estimated the amount of intragenic recombination as population rate (4N(e)r) under the coalescent and found it to be approximately three times higher compared to point mutations (Watterson estimate per gene, 4N(e)mu). Nonindependence of molecular evolution across loci and frequent recombination suggest that MHC class II genes of bony fish may follow different evolutionary dynamics than those of mammals. Our finding of widespread recombination suggests that phylogenies of MHC genes should not be based on coding segments but rather on noncoding introns.
|
|
