Development of osmotically controlled drug delivery system using crosslinked and non-crosslinked hard gelatin capsules

Abstract

The aim of this study was to explore the release characteristics of an elementary osmotic pump capsule (OPC) by using a crosslinked and a noncrosslinked hard gelatin capsule shell. The influences of drug solubility, film thickness and orifice size on drug release from the system were examined. Diltiazem hydrochloride (freely water soluble drug) and propranolol hydrochloride (water soluble drug) were used as the model drugs. Sodium chloride was used as the osmotic agent. Crosslinked hard gelatin capsules were prepared by controlled exposure to formaldehyde vapours. The OPC was prepared by filling the capsule No. 1 with the mixture of the model drug (90 mg), lactose and sodium chloride. Core capsules were coated using hydroxypropyl methylcellulose as subcoating and cellulose acetate as the semipermeable membrane; then the coated capsule was drilled on the rounded end position. Drug release studies were conducted using water, different ionic strength and pH solutions with isotonicity as the dissolution media. Lag time of drug release from the OPC using the crosslinked capsule was longer than that the non-crosslinked capsule shell. Diltiazem hydrochloride OPC using the non-crosslinked and crosslinked capsules could prolong drug release about 9 hours and closed to zero-order drug release rate up to 80 % of drug release (R[superscript 2] > 0.9). Propranolol hydrochloride OPC using a non-crosslinked capsule and a crosslinked capsule could prolong drug release about 9 and 12 hours, respectively. About 90 % of the drug was released as zero-order rate for propranolol hydrochloride OPC (R[superscript 2] > 0.9). It was found that propranolol hydrochloride OPC using the crosslinked capsule shell provided less fluctuations of release rate at various time intervals than using the non-crosslinked capsule. But the characteristics of release rate at various time points of diltiazem hydrochloride OPC prepared using different types of capsule shell was apparently similar. This might be attributed to the higher water soluble property of diltiazem hydrochloride. Ionic strength of dissolution media had effect on drug release of OPC. But drug release of OPC was independent of pH of dissolution media.