Formulation and Evaluation of Modified Pulsincap as Pulsatile Drug Delivery System for Treatment of Rheumatoid Arthritis

Abstract

The aim of the present study was to design and evaluate a modified pulsincap pulsatile drug delivery system of etodolac for treatment of rheumatoid arthritis. Capsule body was made water insoluble by cross linking with formaldehyde vapour. It was filled with drug, osmogen NaCl and super disintegrant sodium starch glycolate to expel the drug after predetermined lag time. A hydro gel plug made of HPMC K4M was placed in the capsule body to achieve desired drug release after lag time for chronotherapy of rheumatoid arthritis. Untreated cap was then fitted to the treated body was sealed. Entire unit was coated with 5% Eudragit S-100 to prevent variable gastric emptying. A 32 full factorial design was used for optimization in which concentration ratio of NaCl and SSG (X1), and the weight of hydrogel plug (X2) were selected as independent variables while lag time and t90% were taken as dependent variables. FTIR and DSC studies confirmed drug excipient compatibility. Developed formulation was evaluated for in-vitro drug release in pH 1.2, phosphate buffer pH 6.8 and phosphate buffer pH 7.4. Statistical analysis confirmed the significance of selected independent variables. Response surface plot and contour plot indicate augmentation of the line toward the weight of hydrogel plug factor indicating greater significance. Formulation with highest desirability containing 34.4 mg of SSG, 137.6 mg of NaCl and 48 mg of HPMC K4M plug was selected as an optimized formulation as it provided the desired lag time of 6 hours and t90% of about 477 mins. Accelerated stability study performed on optimized formulation suggested stable and viable formulation. A stable, efficient formulation modified pulsincap of Etodolac as a pulsatile drug delivery system was developed with proposed increased patient compliance and improved dosage form efficiency.