Development and In vitro-In vivo Characterization of Chronomodulated Multi-Particulate Drug Delivery System of Terbutaline Sulphate for Treatment of Nocturnal Asthma by box–Behnken Statistical Design

Abstract

The objective of the present study was to develop a chronotherapeutic multi-particulate drug delivery system (CMPDDS) of Terbutaline sulphate (TS) intended for treatment of nocturnal asthma attacks. The formulation is capable of simultaneously releasing drug from an immediate release component and a sustain release component. In this study capsules containing immediate release powder blend and sustained release granules containing TS were formulated. Sustained release granules were formulated using Ethyl cellulose (EC), HPMC K15M, and Carbopol 971P. Optimization of sustained release granules was done by response surface methodology employing Box Behnken design. The CMPDDS were evaluated for physical characterization and In vitro drug release studies. The optimized CMPDDS formulation (MP1) was able to sustain the drug release for a period of 12 h. The accelerated stability studies showed no significant changes in physicochemical properties and release behaviour. Further in vivo pharmacokinetic studies were performed on rabbits to determine pharmacokinetic parameters. The formulation MP1 showed Cmax=169.87± 4.133 ng/mL at 4 h Tmax. The area under the curve for the formulation MP1 was 2079.95 ± 41.64 ng.h/mL. It can be concluded from the study that the CMPDDS of TS can be successfully formulated and used for the chronotherapy of nocturnal asthma.