Modified conventional hard gelatin capsules as fast disintegrating dosage form in the oral cavity.

Fast disintegrating capsules for administration in the oral cavity were prepared either by perforation or by vacuum-drying of conventional hard capsules. When compared to other fast disintegrating dosage forms (e.g. lyophilized sponges or tablets), these capsules have various advantages, in particular, a high drug loading capacity and no compression steps. The disintegration time of conventional hard gelatin capsules (HGC) was reduced from 91 to 39 s by introducing 6-10 small holes (diameter =25-50 microm) into the capsule shell. Vacuum-drying of conventional hard gelatin capsules resulted in brittle capsules, which broke rapidly in the oral cavity. The brittleness of the hard gelatin capsules correlated well with their moisture content. The critical moisture value for sufficient brittleness of hard gelatin capsules was <4% w/w. In contrast, HPMC capsules remained flexible, even at low moisture content. The moisture uptake of various capsule fillers was in the order of Avicel PH101 > lactose > Avicel PH112 > or = mannitol. Hard gelatin capsules filled with mannitol and packaged in bottles with silica gel kept their desired brittleness during 6 months storage at various relative humidities.

Preparation and characterization of novel fast disintegrating capsules (Fastcaps) for administration in the oral cavity.

The objective of this study was to prepare novel capsule-based fast disintegrating dosage forms for the oral cavity (Fastcaps). First, cast films were prepared from various additive-containing gelatin solutions and evaluated with respect to disintegration time and mechanical properties in order to identify suitable formulations for the capsule preparation. The disintegration time of films decreased with decreasing bloom strength and could be further decreased by the addition of sugars or PEGs. Fast disintegrating capsules were successfully prepared by a dipping process, whereby parameters such as the viscosity and temperature of the dipping solution and the dipping velocity of the steel pins were optimized. The required viscosity range of the dipping solution for Fastcap manufacturing was 500-600 cP. The addition of the hydrophilic additives (xylitol, sorbitol or PEG 1500) did not significantly affect the viscosity and gelation temperature of the dipping solution. The in vitro disintegration of Fastcaps (30-45 s) was twice as rapid as the one of regular hard gelatin capsules. In vivo, Fastcaps disintegrated rapidly (9-13 s) and their content was spread throughout the oral cavity within seconds. Lactose and/or microcrystalline cellulose were suitable fillers for Fastcaps. The mechanical properties of Fastcaps were similar to commercially available gelatin capsules, which assures good processability and handling.

Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets.

Weakly basic drugs and their salts exhibit a decrease in aqueous solubility at higher pH, which can result in pH-dependent or even incomplete release of these drugs from extended release formulations. The objective of this study was to evaluate strategies to set-off the very strong pH-dependent solubility (solubility: 80 mg/ml at pH 2 and 0.02 mg/ml at pH 7.5, factor 4000) of a mesylate salt of weakly basic model drug (pK(a) 6.5), in order to obtain pH-independent extended drug release. Three approaches for pH-independent release were investigated: (1) organic acid addition in the core, (2) enteric polymer addition to the extended release coating and (3) an enteric polymer subcoating below the extended release coating. The layering of aspartic acid onto drug cores as well as the coating of drug cores with an ethylcellulose/Eudragit L (enteric polymer) blend were not effective to avoid the formation of the free base at pH 7.5 and thus failed to significantly improve the completeness of the release compared to standard ethylcellulose/hydroxypropyl cellulose (EC/HPC)-coated drug pellets. Interestingly, the incorporation of an enteric polymer layer underneath the EC/HPC coating decreased the free base formation at pH 7.5 and thus resulted in a more complete release of up to 90% of the drug loading over 18 h. The release enhancing effect was attributed to an extended acidification through the enteric polymer layer. Flexible release patterns with approximately pH-independent characteristics were successfully achieved.