FORMULATION DEVELOPMENT OF DOLUTEGRAVIR SODIUM LOADED NANO LIPID CARRIERS FOR IMPROVED SOLUBILITY AND PERMEABILITYAbstract
Dolutegravir sodium (DTG) is a poorly soluble antiretroviral drug that belongs to BCS class II approved by the FDA for treatment of HIV infections; however, DTG has several shortcomings, including low solubility in water, low oral bioavailability, hepatotoxicity, and instability in an acidic environment. After oral administration, 84% of the dose is excreted from the body in an unchanged form due to its poor solubility. To overcome the above mentioned difficulties, Nano Lipid Carriers (NLCs) are selected as a potential drug delivery system for the present research work. NLC suspension was formulated using melt emulsification sonication technique using a combination of solid lipid (8% w/v), i.e., Glyceryl monostearate (GMS), Gelucire 50/13, Dynasan 118, and liquid lipid Capmul MCM EP along with a blend of Tween 80 and Span 80 as a surfactant, Sodium cholate (0.4 w/v) as surface charge modifier and BHT (0.01%w/v) as a preservative. Response surface methodology using 23 factorial designs with three independent variables, that is, lipid concentration (A), surfactant concentration (B), sonication time (C) was applied to determine the optimum levels for particle size, entrapment efficiency. Optimized batch NLC-F2 suspension was composed of an 80:20 ratio of solid to liquid lipid and 5% w/v of Tween 80: Span 80 blend in a 70:30 ratio. NLCs were characterized by Scanning Electron Microscopy. The average Particle size of the optimized batch was 123.1 nm with a polydispersity index value of 0.406 and zeta potential -16.1 mV. The DTG loaded NLCs suspension formulation offered good in-vitro release (96.32 % in 48 h) and permeability of (94.02% in 8 h) using the rat intestinal model.
N. A. Shaikh and R. R. Lala *
Department of Pharmaceutics, Prin. K. M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai, Maharashtra, India.
30 June 2020
20 November 2020
06 May 2021
01 July 2021