Push-Pull Osmotic Pumps Using Crosslinked Hard Gelatin Capsule as a Structural Assembly for Delivery of Drugs with Different Water Solubilities

Abstract

The aim of this work was to prepare push-pull osmotic pump capsules using crosslinked hard gelatin capsules as a structural assembly for delivery of four model drugs with different water solubilities including diltiazem hydrochloride, propranolol hydrochloride, ambroxol hydrochloride, and paracetamol. A hard gelatin capsule was crosslinked in formaldehyde vapor for 12 h. Then, a push-pull osmotic pump capsule was prepared, and formulation factors were investigated, i.e., the amount and solubility of model drugs, the amount of polyethylene oxide in pull layer, and size of the capsule. Drug release was evaluated to clarify the release characteristic in several release mediums. Results showed that drug release was independent of drug solubility, drug amount, and capsule size. Almost all of the drug release approached Higuchi’s release model. However, ambroxol hydrochloride could not deliver via this device because of its rather high-density drug particle. Reduction of the polyethylene oxide amount resulted in less drug release. Increasing osmolality of the medium reduced drug release. Drug release studies using a medium with digestive enzymes did not alter drug release compared to medium without enzymes. Push-pull osmotic pump capsules prepared from stored crosslinked hard gelatin capsule shells provided reproducible drug release characteristic. This developed push-pull osmotic pump capsule is an alternative osmotic pump device for delivery of drugs with different water solubilities.