Microemulsion Mediated Synthesis of Nanodrugs for Improved Pharmaceutical Formulations

Abstract

Solubility of Active Pharmaceutical Ingredients (APIs) is one of the major challenges in designing a stable and robust drug formulation for pharmaceutical industry. Low dissolution release profile and poor bioavailability of the drug product are issues raised due to the poor aqueous solubility of APIs. Furthermore, formulating the drug formulation is another challenge faced by pharmaceutical industry. The work reported in the present thesis details successful development of three new oil-in-water (o/w) microemulsion (µE) formulations. Functional nanoparticles (NPs) of selected antibacterial, antihypertensive and antihyperlipidemic drugs were prepared by adopting non-conventional technique of lyophilization of drug-loaded µE formulation. The first μE formulation containing N-butyl acetate (15.0%) / tween 20- lecithin (20.2%) / 2- butanol (30.0%) / water (35.0%) was developed for Irbesartan (IBS, an antihypertensive agent). The second μE formulation comprising N-butyl acetate (6.3%) / polysorbate 80-lecithin (15.8%) / ethanol (31.6%) / water (46.3%) was developed for the preparation of NPs of some selected fluoroquinolone antibiotics (FLQ). The third µE formulation consisting of ethyl acetate (18.0%), ethanol (25.0%), brij (25.0%) and water (32.0%) was developed for Ezetimibe (EZM, an antihyperlipidemic drug). The as-formulated μEs caging selected APIs were further freeze dried and lyophilized to obtain non-aggregated drug-NPs. Multiple complementary characterization techniques, namely, Dynamic Light Scattering (DLS), Scanning Transmission Electron Microscopy (STEM), X-Ray Diffraction (XRD), Spectroscopic measurements (FTIR and Fluorescence), Differential Scanning Calorimetry (DSC), Thermal gravimetric analysis (TGA) and dissolution test were used to study the structural morphology of as-obtained NPs. NPs of API were prepared with particle size less than 100nm determined by DLS and STEM technique. Physical form of drug was changed from crystalline to amorphous confirmed by XRD studies. Reduction in particle size of API was achieved. A tremendous enhancement in dissolution profile (IBS; 99.50%, LVF; more than 90% in all three medias, EZM; 98.11%) and long-term stability of drug-NPs was attained that could be vital for the targeting mechanism of the nanodrugs. The as-adopted methodology is simple, requires no specific step as in conventional formulations and can be integrated for pharmacological engineering