Improvement of dissolution of poorly soluble drugs by solid deposition on a super disintegrant .2. The choice of super disintegrants and effect of granulation

It is demonstrated that the dissolution from capsules and tablets of poorly soluble, hydrophobic drugs can be strongly improved by solid deposition of the drug upon hydrophilic, strongly swelling carriers like the super disintegrants sodium starch glycolate and croscarmellose sodium. As an effect of its lower swelling power, the super disintegrant crospovidone is far less effective than the other super disintegrants. Wet granulation of poorly soluble drugs with high concentrations of sodium starch glycolate resulted likewise in a strongly improved drug release and bioavailability from capsules and tablets. It was found, however, that granules containing a too high concentration of the super disintegrant slow down the drug release from tablets. This effect is caused by the formation of a viscous barrier of the super disintegrant in the granules during the dissolution process

PREPARATION, CHARACTERIZATION AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRINS .5. STUDY ON THE BINDING-PROPERTIES OF AMYLODEXTRIN, METASTABLE AMYLODEXTRIN AND METASTABLE AMYLOSE

Amylodextrin, metastable amylodextrins, Amylose V and metastable amylose were investigated on their dry binding properties. Amylose V showed poor binding properties. Both amylodextrin and metastable amylodextrin produced tablets showing crushing strengths comparable with microcrystalline cellulose, whereas tablets compressed from metastable amylose even showed crushing strengths which were more than 2-fold greater. Both amylodextrin and metastable amylose showed a granular structure composed of very small primary particles (mean diameter 1-2 mu m). During compression the granulates disaggregated into the primary particles. The latter deformed plastically followed by the formation of hydrogen bonds. Plastic deformation was confirmed by force-displacement curves and formation of hydrogen bonds was supported by the observation of increasing binding on increasing moisture content. Neither amylodextrin nor metastable amylose showed susceptibility for magnesium stearate, while Amylose V did show sensitivity for this lubricant. The difference is explained by the higher specific surface area and poorer flowing properties of amylodextrin and metastable amylose, as compared to Amylose V

PREPARATION, CHARACTERIZATION AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRINS .5. STUDY ON THE BINDING-PROPERTIES OF AMYLODEXTRIN, METASTABLE AMYLODEXTRIN AND METASTABLE AMYLOSE

Amylodextrin, metastable amylodextrins, Amylose V and metastable amylose were investigated on their dry binding properties. Amylose V showed poor binding properties. Both amylodextrin and metastable amylodextrin produced tablets showing crushing strengths comparable with microcrystalline cellulose, whereas tablets compressed from metastable amylose even showed crushing strengths which were more than 2-fold greater. Both amylodextrin and metastable amylose showed a granular structure composed of very small primary particles (mean diameter 1-2 mu m). During compression the granulates disaggregated into the primary particles. The latter deformed plastically followed by the formation of hydrogen bonds. Plastic deformation was confirmed by force-displacement curves and formation of hydrogen bonds was supported by the observation of increasing binding on increasing moisture content. Neither amylodextrin nor metastable amylose showed susceptibility for magnesium stearate, while Amylose V did show sensitivity for this lubricant. The difference is explained by the higher specific surface area and poorer flowing properties of amylodextrin and metastable amylose, as compared to Amylose V.</p

PREPARATION, CHARACTERIZATION, AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRIN .3. DRUG-RELEASE FROM FATTY SUPPOSITORY BASES CONTAINING AMYLODEXTRIN

Drug release from fatty suppository bases containing a solid dispersion of diazepam with amylodextrin or a complex of prednisolone with amylodextrin was analyzed in a flow-through model. Being present as a suspension in the fatty base, particles of complex or solid dispersion are transported to the lipid-water interface by sedimentation. After entering the aqueous phase they partially dissolve. The suppositories showed increased drug release compared with the corresponding suppositories containing drug only. Because of the partial solubility of amylodextrin, drug release was lower than the release from drug-cyclodextrin complexes. Use of the soluble fraction of amylodextrin for both the solid dispersion and the complex further enhanced drug release, but it was still below that of drug-cyclodextrin complexes.</p

PREPARATION, CHARACTERIZATION, AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRIN .3. DRUG-RELEASE FROM FATTY SUPPOSITORY BASES CONTAINING AMYLODEXTRIN

Drug release from fatty suppository bases containing a solid dispersion of diazepam with amylodextrin or a complex of prednisolone with amylodextrin was analyzed in a flow-through model. Being present as a suspension in the fatty base, particles of complex or solid dispersion are transported to the lipid-water interface by sedimentation. After entering the aqueous phase they partially dissolve. The suppositories showed increased drug release compared with the corresponding suppositories containing drug only. Because of the partial solubility of amylodextrin, drug release was lower than the release from drug-cyclodextrin complexes. Use of the soluble fraction of amylodextrin for both the solid dispersion and the complex further enhanced drug release, but it was still below that of drug-cyclodextrin complexes

CONTROLLED-RELEASE OF THEOPHYLLINE MONOHYDRATE FROM AMYLODEXTRIN TABLETS - IN-VITRO OBSERVATIONS

Amylodextrin is a linear dextrin and can be produced by enzymatic hydrolysis of the alpha-1,6 glycosidic bonds of amylopectin. Tablets compacted from pure amylodextrin showed good binding properties and did not disintegrate in aqueous media. Extended and decreasing drug release rates were found for tablets of 300 mg with a diameter of 9 mm containing 70% amylodextrin and 30% theophylline monohydrate, when compacted at 5 kN. Almost-constant drug release rates were obtained for these tablets when compacted at 10 or 15 kN. Nearly constant drug release rates were also shown for amylodextrin tablets with a drug load up to 75% compacted at 10 kN. Both release rate and release profile could be adjusted by selecting tablet thickness and incorporation of either lactose as a highly soluble excipient or talc as a hydrophobic excipient.</p