Preparation Of Oral Fast Dissolvable Film Of Donepezil Hydrochloride

Objectives:To establish and evaluate the formulation and preparation method of donepezil hydrochloride-loaded oral fast dissolving film(DPL-ODF).Methods:The pre-formulation studies of DPL were performed to establish HPLC assay method,the calibration curve of DPL was prepared,and the compatibility of DPL and excipients were investigated.Different ratios of combined polymers composed of maltodextrin and pullulan for ODF were observed to optimize the formulation via orthogonal design method using solvent casting technique.The pharmaceutical properties of DPL-ODF were characterized,such as appearance,weight variations,the micro-structures,mechanical profiles and the dissolution test in simulated saliva fluid.Finally,the preliminary stability test of DPL-ODF was carried out.Results:The HPLC determination method of DPL was stable and reliable.The precision and recovery of DPL could meet the requirements.DPL had good stability in various stressed condition which including high temperature,high humidity and strong light conditions.The optimized formulation and process for DPL-ODF were as follows,API/film-forming material(1:8),MDX/Pullulan(1:9),propylene glycol(20%),drying temperature(40℃)using solvent casting method.The thickness of ODF prepared in the experiment was 75.6±1.36 μm and disintegration time was 9.8±2.5 s.The elastic modulus,tensile strain and tensile stress were 225 ± 119.6 MPa,3.5 ± 0.02 mm·mm-1 and 5.1 ± 1.7 MPa.The drug uniformity in each film(2×3 cm2)was satisfied.Biological microscope observation indicated that DPL-ODF was a compact with smooth surface.The release rates of DPL-ODF in simulated saliva fluid(PBS,pH 6.8)at 3 min and 5 min were 95.1±3.2%and 103.2±4.1%,respectively,which could meet the requirements of ODF.Conclusion:DPL-ODF was successfully prepared by solvent casting method using a combination of maltodextrin and pullulan at appropriate ratio.The appearance,mechanical properties and disintegration of DPL-ODF could all meet specification,and the release in vitro was satisfactory.However,due to the variation of the release rate of DPL-ODF,it is necessary to continue screening and investigate the formulation,preparation process and preservation conditions.