Development of osmotically controlled drug delivery capsules

Abstract

Osmotic system of coated hard gelatin capsule was developed. Gelatin capsule shell was coated by fluidized bed coater using hydroxypropylmethylcellulose and cellulose acetate as subcoating layer and semipermeable membrane, respectively. Propranolol hydrochloride was used as a model drug. NaCl, KC1, lactose and sucrose were used as osmotic agents. Various influential factors ie. orifice size, amount of plasticizer, amount of osmotic agent, osmotically active dissolution medium were investigated. PEG400 was used as plasticizer and pore forming agent. SEM photomicrograph shows porous cellulose acetate membrane after coated capsule contacted the water. The drug release increased as amount of PEG400 was increased as PEG400 could leach out from the cellulose acetate film due to hydrophilic property causing porous structure of the membrane. At the low thickness of coating membrane, the orifice size influenced dramatically on drug release. On the contrary, the orifice size influenced slightly on drug release at the high thickness of coating membrane. The drug release rate increased when amount of sodium chloride in formulation was increased. Whereas, the drug release rate of formulation containing lactose was the highest. Sodium chloride in the formulation might induce aggregation of dissolved gelatin shell due to interaction between gelatin and sodium chloride resulting in obstructing water influx into the coated capsule hence less drug release. Whereas, lactose did not induce aggregation of dissolved gelatin shell resulting in higher drug release. When osmotic pressure of dissolution medium was increased, the drug release decreased. Decreased osmotic pressure difference across the membrane might be a cause of slower drug release rate