1.
Unga, Johan, 1976, et al.
(författare)
Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions
2009
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 73:2, s. 260-268
Tidskriftsartikel (refereegranskat) abstract
The solid state behaviour of polyethylene glycol 4000 (PEG 4000) and dispersions of a homologous series of parabens (methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- (BP)) were examined and compared to the paraben solubility in liquid PEG 400. Dispersions were prepared by co-melting different amounts of paraben (5-80% (w/w)) and PEG 4000 and were studied using a combination of differential scanning calorimetry (DSC) and small and wide angle X-ray diffraction (SAXD/WAXD). Depending on the concentration of parabens in the dispersions, DSC showed melting peaks from folded and unfolded forms of PEG, a eutectic melting and melting of pure parabens. The fraction of folded PEG increased and the melting temperatures of both PEG forms decreased with increasing paraben content. In an apparent phase diagram of PP-PEG dispersions a eutectic mixture appeared above 5% PP. In addition, a melting peak corresponding to the paraben appeared for dispersion containing more than 60% PP. Similar phase diagrams were shown for the other parabens. The SAXD data and a 1D correlation function analysis revealed that MP and BP were incorporated into the amorphous domains of the lamellae of solid PEG to a higher degree than EP and PP. In addition, the lamellae thickness of PEG and the fraction of amorphous domains increased more for MP and BP compared to EP and PP. BP showed the highest solubility of the parabens followed by MP, EP and PP in both liquid and solid PEG. Furthermore, the thickness of the amorphous domains of the PEG in the different parabens-PEG dispersions could be correlated to the solubility in liquid PEG 400.
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.
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.
5.
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
6.
Bramer, Tobias, et al.
(författare)
Implications of regular solution theory on the release mechanism of catanionic mixtures from gels
2009
Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 71:2, s. 214-225
Tidskriftsartikel (refereegranskat) abstract
The aim of this study was to apply the regular solution theory of mixed micelles to gain new insights on the drug release mechanism, when using catanionic mixtures as a method of obtaining prolonged release from gels. Synergistic effects were investigated at equilibrium and quantified in terms of regular solution theory interaction parameters. The drug release from catanionic aggregates was studied both in a polymer free environment, using dialysis membranes, and in gels, using a modified LISP paddle method. The drug release kinetics was modelled theoretically by combining the regular solution theory with Fick's diffusion laws assuming a contribution to the transport only from monomeric species (stationary aggregates). The theoretical predictions were found to be in reasonably good agreement with experiments. An analysis of the calculated distribution of species between aggregated and monomeric states was shown to provide further insights into the release mechanism.
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.
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.
9.
10.
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.
