Development of chronotherapeutic formulation for anti-asthmatic drugs

Abstract

The main objective of this work was to develop an oral chronotherapeutic drug delivery system containing anti-asthmatic drugs. In the first phase, effect of various types of cellulose derivative polymers in the presence of Mg stearate as a coating material was studied by using Taguchi design of experiment with theophylline anhydrous as a model drug. HPMC K100, HPC, NaCMC and HEC were included as hydrophilic polymers and EC as hydrophobic polymer in the presence or absence of Mg stearate. According to the statistical prediction, the optimal values obtained were: HPC for type of hydrophilic polymer, hydrophilic polymer/EC ratio in the range of 2.5: 1 to 4: 1 and Mg stearate in the range of 26-30mg. Since, the results from optimization studies were found to be in wider range and suggested further studies to arrive at the optimal settings. Hence in the second phase, a D-optimal design of experiment was employed to identify the optimal composition of ternary blend of EC, HPC and Mg stearate as outer coating material. As response variables % drug release at 8hr, % drug release at 10hr and time required in hr for 10% of drug release (lag time) were considered. The design was quantitatively evaluated by quadratic model and the results of statistical analysis revealed that the interaction factors between EC-HPC and HPC-Mg stearate were found to be highly significant on the studied response variables. In the third phase, the effects of pH, time and enzyme dependent polymers as coating materials were evaluated for formula composition in the preparation of press-coated tablets containing theophylline anhydrous as a model drug by using D-optimal design of experiment.