Abstract

FORMULATION AND DEVELOPMENT OF MICROEMULSION OF RALOXIFENE FOR NASAL DRUG DELIVERY

Kasturi* and Samip Shah

ABSTRACT

Raloxifene (RLX) is a selective estrogen receptor modulator, currently used in the prevention as well as treatment of osteoporosis in post menopausal women. By virtue of extensive pre-systemic clearance, limits its absolute bioavailability to only 2 % after 60 mg dose. The objective of present investigation was to develop and evaluate microemulsion (ME) of RLX to overcome these issues. The solubility of RLX in oils and surfactants was evaluated to construct pseudo ternary phase diagram by detecting the area for preparation of microemulsion and its optimization done by 32 factorial design. Under the factorial design, 9 formulations were primarily prepared by titration method taking concentration of oil as first independent factor (X1) as well as concentration of surfactant mixture (X2) as second independent factor and were evaluated for globule size and % transmittance as two dependent factors Y1 and Y2 respectively. The optimized formula of Raloxifene loaded Oil-in-water (o/w) microemulsion containing 5% oil (Capmul MCM), 48.15% surfactant mixture (Tween-80 : PEG-200, 2:1) and 46.85% distilled water was formulated and characterized for %transmittance, pH, viscosity, density, centrifugation, globule size, drug content and in-vitro release. It was found that optimized microemulsion was stable and transparent with average globule size of 58.9 nm, zeta potential of +20 mV, polydispersity index (PDI) of 0.35 and showed no toxicity during histopathological evaluation on sheep nasal mucosa. Hence, by formulating into microemulsion, the solubility of raloxifene was significantly enhanced.

Keywords: Factorial design, Microemulsion, Optimization, Pseudoternary phase diagram, Raloxifene, Solubility.