A Method to Prepare Solid Lipid Nanoparticles with Improved Entrapment Efficiency of Hydrophilic Drugs

摘要

Introduction: Premise of the present study was to suitably select or modify the constitution of the lipid matrix to achieve significantly high entrapment of hydrophilic drugs within solid lipid nanoparticles (SLNs). Methods and Materials: Isoniazid was selected as a representative hydrophilic drug with a high solubility of 230 mg/ml and a log P of -0.402 at 25℃ (determined as per OECD TG 105 and 107 respectively). Three lipids/fatty acids (Glyceryl monostearate, Compritol 888 ATO and stearic acid) were evaluated out of which Compritol 888 ATO and stearic acid showed favorable interactions (FTIR and DSC studies) with isoniazid. The two lipids were used alone or in combination for preparing SLNs. Formulation of SLNs by microemulsification, method involved pouring the hot micro-emulsion into cold water under constant stirring, which may result in expulsion of the hydrophilic drug from the lipid matrix; hence, partitioning of isoniazid from the hot lipid melts into cold water was also determined. Results and Discussion: Results indicate that combining stearic acid with Compritol 888 ATO in certain ratio (1:4) led to significant entrapment efficiency (EE) of 84.0±1.1%. The formulations were subjected to morphological, physiochemical and in vitro drug release studies. Developed SLNs were found to be stable for 1 year at 4℃. Conclusion: The study demonstrates the benefit of excipient screening techniques in improving entrapment efficiency of a hydrophilic drug.