FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF SOLID LIPID NANOPARTICLES OF GEMCITABINE HYDROCHLORIDE

Abstract

Gemcitabine Hydrochloride is a BCS class III drug of choice in the treatment of cancer, as a single or in combination chemotherapy. However, its bioavailability is a major concern due to its short half-life. Solid lipid nanoparticles (SLN) of Gemcitabine Hydrochloride were prepared to enhance its bioavailability, hence anticancer activity. The Quality by Design approach was applied for the formulation of SLN. The Randomized 3² factorial design was used with responses of particle size and % entrapment efficiency (% EE). The optimized batch of Gemcitabine Hydrochloride loaded SLN containing 1gm of GMS as solid lipid, 1gm of Tween80: Sodium Taurocholate as surfactant:co-surfactant and 5mg of Gemcitabine Hydrochloride was prepared by high shear homogenization method followed by Probe sonication for 15min to form nanoparticulate SLN dispersion. The Optimized batch of Gemcitabine Hydrochloride loaded SLN that exhausted mean particle size of 126.1nm, zeta potential -28.6 mV and % EE 74.83% respectively. SEM studies revealed three-dimensional nature of SLN with a slightly rough surface. DSC, results exhibited entrapment of Gemcitabine Hydrochloride in SLN. The optimized batch of SLN was evaluated for in-vitro % drug release using cellulose membrane dialysis bags for 24hrs and showed 63.13% CDR at 24 hrs. Anticancer cell line studies were also performed in human lung cancer cell line (A-549). It concludes that Gemcitabine Hydrochloride loaded Solid lipid Nanoparticles was successfully formulated and evaluated to sustain the drug release by bypassing the first pass metabolism.

Key words: Gemcitabine Hydrochloride, SLN, QbD, High shear homogenization, anticancer activity.