Preparation and Evaluation of Controlled Porosity Osmotic Pump Tablets of Doxofylline Using Fractional Factorial Design: Recent Development

Over the past few decades, oral controlled-release formulations were developed due to their natural, convenience and ease of administration with patient acceptance and safety due to its cost-effective manufacturing process. Many pharmaceutical products for oral delivery are immediate release type which does not control the release of drug and absorption. The study involves the formulation and optimization of Doxofylline Controlled Porosity Osmotic Pump Tablets by using a Fractional Factorial design with an aim to achieve zero-order release and reduce dosage frequency. Doxofylline core tablets were formulated by wet granulation method using HPMC K100M, Polyvinyl Pyrrolidone K30 and Potassium chloride, and sodium chloride as Osmogens. Core tablets were coated with Cellulose Acetate as a Semi-permeable membrane and Sorbitol and PEG 400 as pore-forming agents. Formulations were optimized by using a Fractional Factorial design, with the effect of formulation variables like different ratios of osmogens and polymer concentration in the core tablet. Eight formulations were developed and evaluated for physicochemical parameters and in-vitro drug release. Drug–excipient compatibility was performed by Fourier transform infrared spectroscopy and differential scanning calorimetry. From the in-vitro dissolution data formulation DF1 batch was optimized showing 100.0± 0.64 % drug release in 24 hrs and exhibited zero order kinetics. The release was independent of the pH and agitational intensity. SEM studies showed the formation of pores in Semi-permeable membranes. As the drug peak is retained in the optimized formulation this study proved that there is no incompatibility between the drug and excipients used in the formulation. From these studies, it was concluded that drug release from the osmotic drug delivery system is independent of physiological conditions and hydrodynamical conditions of the body. The desired zero-order release rate was obtained by optimizing the number of osmogens and polymer concentrations. Moreover, with an increase in polymer concentration drug release was decreased and with an increase in concentration of osmotic agent increased drug release rate was observed which indicates the mechanism of drug release was due to osmotic pressure created by the osmotic agent.