1.
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.
2.
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)
3.
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.
4.
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.
5.
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.
6.
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.
7.
Fichtner, Frauke, et al.
(författare)
Effect of surface energy on powder compactibility
2008
Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 25:12, s. 2750-9
Tidskriftsartikel (refereegranskat) abstract
PURPOSE: The influence of surface energy on the compactibility of lactose particles has been investigated. MATERIALS AND METHODS: Three powders were prepared by spray drying lactose solutions without or with low proportions of the surfactant polysorbate 80. Various powder and tablet characterisation procedures were applied. The surface energy of the powders was characterized by Inverse Gas Chromatography and the compressibility of the powders was described by the relationship between tablet porosity and compression pressure. The compactibility of the powders was analyzed by studying the evolution of tablet tensile strength with increasing compaction pressure and porosity. RESULTS: All powders were amorphous and similar in particle size, shape, and surface area. The compressibility of the powders and the microstructure of the formed tablets were equal. However, the compactibility and dispersive surface energy was dependent of the composition of the powders. CONCLUSION: The decrease in tablet strength correlated to the decrease in powder surface energy at constant tablet porosities. This supports the idea that tablet strength is controlled by formation of intermolecular forces over the areas of contact between the particles and that the strength of these bonding forces is controlled by surface energy which, in turn, can be altered by the presence of surfactants.
8.
9.
Frenning, Göran, et al.
(författare)
An effective-medium analysis of confined compression of granular materials
2009
Ingår i: Powder Technology. - : Elsevier BV. - 0032-5910 .- 1873-328X. ; 194:3, s. 228-232
Tidskriftsartikel (refereegranskat) abstract
A simplified model for confined compression of granular materials is considered, which idealizes the collection of particles as a (central) force network. Applying an effective-medium procedure, an equation with micromechanically well-defined parameters is derived, which relates the applied pressure to the engineering strain of the powder during uniaxial compression. Despite the simplicity of the model, comparison with experimental data for mm-sized spherical granules indicates that this equation is able to satisfactorily predict the overall compression profile from single-particle data.
10.
Frenning, Göran, et al.
(författare)
Aspects of pharmaceutical physics
2009. - 5
Ingår i: Modern Pharmaceutics, Volume 2. - New York : Informa Healthcare USA. - 9781420065688
Bokkapitel (övrigt vetenskapligt/konstnärligt)
