Effect of Cellulose Acetate (CA-398-10 NF/ EP) on Osmotically Controlled Drug Delivery System of Amitriptyline

Abstract

Background: Amitriptyline hydrochloride is a Tricyclic Antidepressant (TCA) belonging to BCS class I exhibiting only 30-60% bioavailability and often coupled with poor patient compliance. The primary objective was to develop a formulation with commercial viability and to reduce dosing frequency in order to promote adherence of depressed patients to the treatment regime. The study also focused on reducing the dose of amitriptyline by controlling the release using osmotic technology; thereby reducing the side effects of amitriptyline. Methods: Controlled Porosity Osmotic Pump (CPOP) systems eliminate the need for expensive drilling processes and in turn are apt for industrial manufacturing systems where as other osmotic systems have practical limitations. Wet granulation technique was used for the formulation of CPOP tablets of amitriptyline as burst release was observed in directly compressed tablets. Screening of polymers, osmogen and weight gain were performed. Results: F6-D3 (3 % Di-butyl phthalate) with lactose as osmogen and HPMC K 35 M as polymer was optimized. The drug release from the optimized formulation was found to be independent of the effect of agitational intensity and pH. To confirm the osmotic release mechanism, the osmotic pressure of the dissolution medium was increased. The drug release decreased markedly due to an increase in osmotic pressure. Conclusion: Accelerated Stability studies were carried out in ICH certified stability chambers as per the specifications and were found to be stable. It was evident that osmotic pressure generated within the CPOP tablets along with the controlled formation of pores using Cellulose Acetate (CA-398-10 EP/ NP) was able to control the release of amitriptyline hydrochloride for 24 hours. Thus, the Oral Osmotic Drug Delivery system is a promising technology for product life-cycle strategies.