Formulation Optimization and Pharmacokinetic Studies of an Enteric Coated Sustained Release Mucoadhesive Tablet of Zaltoprofen

The objective of present study was to prepare and evaluate Zaltoprofen (ZLT) enteric coated oral mucoadhesive sustained release (SR) tablet in order to improve its GI residence time and improve its bioavailability by using natural biopolymers like xanthan gum and semisynthetic polymer HPMC for its safe use in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis condition. The sustained release polymers, hydroxypropyl methylcellulose (HPMC) of different viscosities and xanthan gum evaluated in different proportions as a major matrix material. Drug-polymer compatibility studies by FTIR and DSC gave confirmation about their purity and showed no interaction physically between drug and selected polymers. ZLT matrix tablets were prepared by wet granulation.  The effect of polymer concentration on the drug release profile and in-vitro bioadhesion of the matrix tablets was studied. A 32 full factorial design was utilized in the optimizing the levels of HPMC and Xanthan gum. Concentration of HPMC K4M and the concentration of xanthan gum per tablet were used as the independent variables.  The dependent variables were the bioadhesive strength, percent drug dissolved at 2, 6 and 10 hours. The data obtained were fit to a model and polynomial equations were generated. Response surface graph was generated based on these equations. Formulation composition with desired release characteristics and bioadhesive strength were found to be predictive using this model. The optimized factorial batch was further given the coating of Opadry® enteric (94 series) polymer in order to avoid GI disturbances. The Z-22 tablets were kept for stability study at 40°C ±2°C and 75% ± 5% RH for a period of 6 months according to ICH guidelines. The formulation was found to be stable after 6 months of study. The pharmacokinetic parameters Cmax, Tmax, Mean Residence Time (MRT) and Area under Curve (AUC) of developed SR tablet were found to be improved with significant difference (p