An Experimental Study on the Development and Evaluation of Mucoadhesive Microspheres for Controlled Drug Delivery

A new strategy of prolonging the residence time of drug in the absorption site and/or sustained therapeutic delivery is the development of mucoadhesive microspheres. The present study was conducted to develop the mucoadhesive microspheres by systematic optimization of formulation and process variables using statistical experimental design and to evaluate the microsystems for safety, efficacy and clinical translational potential in an extensive manner. The microspheres were formulated using the model drug Pioglitazone maleate and the formulation components, chitosan and β-Cyclodextrin through modified emulsion–lyophilization method. Four independent variables (polymer, enhancer, mixing speed, and freeze-drying temperature) at four levels were investigated using four 2⁴ factorial experimental designs for nine formulations. The characterization included particle size analysis, determination of entrapment efficiency, mucoadhesion, in vitro wash-off test and the drug release kinetics were performed in simulated gastric fluid. The surface morphology was studied using scanning electron microscopy, and the chemical compatibility using Fourier transform infrared spectroscopy and differential scanning calorimetry. The results showed that the sodium carboxymethyl cellulose formulations showed maximum mucoadhesion (94.33±2.33% after 1 hour) having particle size range of 31.20±1.88 to 47.54±3.24 μm and entrapment efficiencies range from 54 to 80%. The drug release was controlled and extended with the formulations releasing 91.45±2.55% to 83.43±2.55% of drug in 10 hours. This developed microsphere system also showed good mucoadhesive properties, distinct spherical morphology and a sustained drug-release profile adequate for gastrointestinal delivery. Such observations provide bio-science validation of the development of mucoadhesive microsphere technology for clinical application to diseases that require long residence time within the mucosa and controlled bioavailability.