Crosslinked hard gelatin capsule as a structural assembly of elementary and push-pull osmotic pump delivery system

Abstract

The objective of this study was to characterize the crosslinked hard gelatin capsules in order to use as a structural assembly of osmotic pump capsules for delivery of different water solubility model drugs including diltiazem hydrochloride, propranolol hydrochloride, ambroxol hydrochloride, and paracetamol. The hard gelatin capsules (HGCs) were crosslinked by exposure to formaldehyde vapor for 6, 12, and 24 hours. According to the results, the HGC shell crosslinked for 12 hours was selected for preparation of elementary osmotic pump (EOP) and push-pull osmotic pump (PPOP) due to its insoluble property, low formaldehyde residue, stability after storage, and providing reproducible drug release profiles. Drug release from EOP capsules was dependent of drug substance type and loading dose except diltiazem hydrochloride, a very highly water soluble drug. Drug release from PPOP capsules was independent of drug substance type, loading dose, and capsule size. But it was dependent of amount of polyethylene oxide in a pull layer. The osmolality of release medium affected drug release from PPOP capsules more than from EOP capsules. Drug release study using a medium with digestive enzymes did not alter drug release compared to medium without enzymes. EOP and PPOP capsules prepared using 12-month stored crosslinked HGCs gave consistent release profiles compared to those prepared using initial crosslinked HGCs. Almost all of the formulations gave drug release approaching Higuchi’s release kinetic model. However, ambroxol hydrochloride could not deliver via these devices because of its high dense drug particle. In summary, the developed EOP and PPOP capsules were an alternative osmotic device that could be used for drug delivery systems and were applicable for several drugs with different water solubilities.