1.
Persson, Ann-Sofie, et al.
(författare)
Powder Compression Properties of Paracetamol, Paracetamol Hydrochloride, and Paracetamol Cocrystals and Coformers
2018
Ingår i: Journal of Pharmaceutical Sciences. - : ELSEVIER SCIENCE INC. - 0022-3549 .- 1520-6017. ; 107:7, s. 1920-1927
Tidskriftsartikel (refereegranskat) abstract
The objectivewas to study the relationship between crystal structure, particle deformation properties, and tablet-forming ability for the monoclinic formof paracetamol (PRA), 2 cocrystals and a salt crystal of PRA in addition to 2 coformers (oxalic acid and 4,4'-bipyridine). Thus, the structure-property-performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery. The plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as crystals containing slip planes. In addition, crystals containing slip planes displayed both high and low plasticity. The mechanical properties could not be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity. Furthermore, the elastic deformation could not explain the tablet-forming ability. It was concluded that no relationship between structure-property-performance for PRA and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship, an improved knowledge of crystallographic structure and interparticle bonding during compaction is needed.
2.
Adane, M., et al.
(författare)
The use of extragranular disintegrants in multiple-unit tablet formulations : effect on compressibility, compactibility and disintegration
2007
Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 279-284
Tidskriftsartikel (refereegranskat) abstract
Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.
3.
Alderborn, Göran, et al.
(författare)
Mechanical strength of tablets
2008. - 3
Ingår i: Pharmaceutical Dosage Forms. - New York : Informa Healthcare. - 9780849390166 - 0849390168
Bokkapitel (övrigt vetenskapligt/konstnärligt)
4.
5.
Andersson, Sara B. E., et al.
(författare)
Determination of Intrinsic Drug Dissolution and Solute Effective Transport Rate during Laminar Fluid Flow at Different Velocities
2021
Ingår i: Pharmaceutics. - : MDPI. - 1999-4923 .- 1999-4923. ; 13:6
Tidskriftsartikel (refereegranskat) abstract
The objective of this study was to determine the intrinsic drug dissolution rate (IDR) and the solute effective transport rate of some drugs, using a single particle dissolution technique, satisfying qualified dissolution conditions. The IDR of three poorly water-soluble compounds was measured in milli-Q water using four different fluid velocities. The enveloped surface area of the particles was calculated from the projected area and the perimeter of the particle observed in the microscope. Furthermore, computational fluid dynamics (CFD) simulations were used to theoretically investigate the flow conditions and dissolution rate, comparing box shaped particles and spherical particles with similar dimensions and surface area as the particles used the experiments. In this study, the IDR measurement of the single particles was determined within 5-60 min using particles with an initial projected area diameter (Dp) between 37.5-104.6 mu m. The micropipette-assisted microscopy technique showed a good reproducibility between individual measurements, and the CFD simulations indicated a laminar flow around the particles at all flow velocities, even though there were evident differences in local particle dissolution rates. In conclusion, the IDR and solute effective transport rate were determined under well-defined fluid flow conditions. This type of approach can be used as a complementary approach to traditional dissolution studies to gain in-depth insights into the dissolution process of drug particles.
6.
Andersson, Sara B. E., 1987-
(författare)
Novel and refined small-scale approaches to determine the intrinsic dissolution rate of drugs
2021
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Many drugs are administered as crystalline particles compressed into tablets and taken orally. When the tablet reaches the gastrointestinal tract, it disintegrates and the drug particles dissolve in the gastrointestinal fluid. The dissolved molecules are absorbed across the intestinal membranes into the bloodstream to reach their target sites. Only dissolved molecules can be absorbed, and if a drug has low solubility and/or dissolution rate in gastrointestinal fluid, the drug absorption might be insufficient. Hence, knowing the solubility and dissolution behaviour of a potential drug candidate is necessary early in the drug development process. The aim of this thesis was to evaluate and refine different approaches for measuring and determining dissolution rate, as well as to develop novel in vitro small-scale dissolution methods. First, interlaboratory variability in determination of intrinsic dissolution rate (IDR) and apparent solubility (Sapp) was investigated using a miniaturized dissolution instrument. To minimize the interlaboratory variability, standardized protocols for both the experimental design and the data analyses were required, and a flow chart for performing standardized powder and disc IDR measurements was established. Next, as an alternative to the powder and disc methods, carefully dispersed suspensions were used to determine the IDR, and rapid and more controlled IDR measurements were obtained using suspensions with dispersed primary particles. From the suspension measurements, an IDR/Sapp ratio of the compounds were determined. This ratio can potentially be used to identify whether a compound is likely to show dissolution rate-limited absorption and hence is sensitive to particle size reduction. The final experiments used a single particle dissolution approach to determine the IDR at four different fluid velocities. Computational fluid dynamics (CFD) simulations were used to theoretically investigate the flow conditions and dissolution rates. Single particle dissolution measurements under well-defined conditions gave high-quality dissolution data. An IDR was determined within 5-60 minutes using particles with initial diameters of 37.5-104.6 μm. The single particle dissolution experiments were used to determine the thickness of the effective hydrodynamic boundary layer (heff). The heff values were also assessed by CFD simulations, and a good concordance between experimental and simulated heff values was obtained. The approaches presented in this thesis can be used to derive qualified knowledge about the dissolution properties of drugs with several potential applications in drug development, such as profiling of solid drugs, informed formulation decisions, assisting the modelling of drug dissolution and providing improved understanding of the in vivo-dissolution behaviour
7.
8.
Berggren, Jonas
(författare)
Engineering of Pharmaceutical Particles : Modulation of Particle Structural Properties, Solid-State Stability and Tabletting Behaviour by the Drying Process
2003
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Relationships between stresses during the drying process, particle structural and functional properties, and particle engineering by the drying process were addressed in this thesis. In the first part, the importance of the drying phase and the effect of the drying rate on the intragranular porosity of microcrystalline cellulose pellets were investigated. Differences in porosities of dried pellets could be explained by liquid-related differences in densification during convective drying rather than by differences in densification during wet agglomeration. An increased drying rate gave more porous pellets with a lower compression shear strength, and thereby stronger tablets. The next part dealt with modulation of solid-state stability and tabletting behaviour of amorphous lactose by incorporation of different polymers by spray drying. Increased content and molecular weight of poly(vinylpyrrolidone) (PVP) resulted in an increased resistance to crystallisation provoked by heat and moisture. The stabilising effect was even more evident after long-term storage. However, the glass transition temperature was almost unaffected and may, therefore, be questioned as a stability indicator for these types of materials. The presence of the polymers resulted in somewhat less deformable particles. Incorporation of PVP increased the compactability, whilst a surfactant decreased it, which could be shown to be related to differences in particle-particle adhesivity between the different particles. This thesis contributes to increased mechanistic understanding in the area of particle engineering that may lead to better prediction and optimisation of the functionality of pharmaceutical particles, which is of the utmost importance in the development and production of solid dosage forms.
9.
Elversson, Jessica, 1972-
(författare)
Spray-Dried Powders for Inhalation : Particle Formation and Formulation Concepts
2005
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Spray drying is a method with a high potential in the preparation of protein particles suitable for pulmonary delivery. However, surface induced denaturation of bio-molecules during atomization and subsequent drying can be substantial and it is therefore important to develop new formulation concept for concurrent encapsulation and stabilization of proteins during spray drying. Hence, with an overall objective to increase the knowledge of the formation of particulate systems for systemic administration of proteins by spray drying, the first part of this thesis, systematically investigated the particle formation by droplet size and particle size measurements. It was described how specific properties, such as the solubility and the crystallization propensity of the solute, can affect the product, e.g. the particle size, internal structures, and possibly particle density. A new method using atomic force microscopy (AFM) for the assessment of the effective particle density of individual spray-dried particles was demonstrated. In the second part, two different formulation concepts for encapsulation of protein during spray drying were developed. Both systems used non-ionic polymers for competitive adsorption and displacement of protein from the air/water interface during spray drying. The aqueous two-phase system (ATPS) of polyvinyl alcohol (PVA) and dextran, and the surface-active polymers, hydroxypropyl methylcellulose (HPMC) and triblock co-polymer (poloxamer 188) used for in situ coating, proved efficient in encapsulation of a model protein, bovine serum albumin (BSA). Inclusion of polymeric materials in a carbohydrate matrix also influenced several particle properties, such as the particle shape and the surface morphology, and was caused by changes in the chemical composition of the particle surface and possibly the surface rheology. In addition, powder performance of pharmaceutical relevance, such as dissolution and flowability, were affected.
10.
Fichtner, Frauke, et al.
(författare)
Drug release from compacted single inert matrix agglomerates
2007
Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 273-277
Tidskriftsartikel (refereegranskat) abstract
The effect of compaction on the drug release from single, sodium chloride loaded, microcrystalline cellulose agglomerates of different porosities was investigated in this study. The drug release from uncompacted agglomerates and from agglomerates regained from tablets compacted at a range of different compaction pressures was monitored measuring the conductivity of the dissolution medium in a recirculation flow-through system. The drug release profiles were described using the mean dissolution time (MDT), the variation of dissolution time (VDT) and the relative dispersion coefficient (RD). It was found that depending on physical structure changes of the matrix, the drug release rate of compacted agglomerates could be enhanced or retarded in comparison with uncompacted agglomerates. The retardation is suggested to be due to a densification of the matrix and the enhancement due to a crack formation in the external surface of the matrix.
