Development and evaluation of push-pull based osmotic delivery system for pramipexole.

摘要

An oral push-pull system that can deliver pramipexole for extended period of time has been developed and characterized. A bilayer osmotic drug delivery system was developed using a basic design consisting of an oral controlled porosity osmotic pump. Unlike other osmotic systems, which require a preformed orifice for drug release, controlled porosity membranes contain water-soluble pore-formers in the coating membrane. When such systems come in contact with water, the additives dissolve resulting in an in-situ formation of a microporous membrane. The push layer swells releasing the drug at a controlled rate. In advanced Parkinson's disease the usual dose of pramipexole is 1.5 mg three to four times a day. Hence, an attempt was made to develop a once-a-day controlled release system. This may offer significant patient benefits by providing enhanced efficacy and reduced side effects and may also reduce the number of daily doses compared to conventional therapies. This developed push-pull system was compared with other types of osmotic delivery systems, such as an asymmetric membrane coating and a dense coat with mechanical drilling. An optimized system was selected to study the effect of the concentration of a pore-forming agent such as PEG 400 and dibutyl phthalate, the pH of dissolution media, the effect of agitation and osmotic agents on drug release. The osmotic pressure generated was determined using a 3D3 freezing point osmometer. The drug release was found to follow zero order kinetics. Drug release increased with an increase in osmotic pressure. The developed push-pull osmotic system showed the desired once-a-day release kinetics.