FABRICATION AND STATISTICAL OPTIMIZATION OF LIPID-BASED NANOPARTICLES FOR THE ENCAPSULATION OF DOLUTEGRAVIR SODIUMAbstract
Dolutegravir, an integrase strand transfer inhibitor (INSTI), is a BCS class II, poorly soluble antiretroviral medication that has been licenced by the FDA for the treatment of HIV infections. DTG has a number of drawbacks, including limited oral bioavailability (16%), hepatotoxicity, and instability in an acidic environment. Due to the medication’s limited solubility, 84% of the dose is eliminated from the body after oral administration in an unaltered state. Lipid-based nanoparticles have been chosen for the current research study as a viable drug delivery technology to help with the aforementioned challenges. Melt emulsification sonication procedure was used with CAPMUL MCM EP, Glyceryl monostearate, TWEEN 80, SPAN 80, and other ingredients, a total of six formulations were created. The formulations’ particle size, polydispersity index, zeta potential, drug concentration, drug entrapment effectiveness, in-vitro release, and other factors were assessed. The prepared formulations demonstrated zeta potential of -11.78 to-26.6, in-vitro drug release of between 62 and 80.32 percent, and particle sizes varying from 155 to 205 nm. The best formulation, according to the early trial, was F2. Particle size Y1 and in-vitro drug release Y2 were two dependent variables, and F2 was fitted to a 22 factorial design with two independent factors, concentration of span 80 – X1 and sonication duration – X2. 4 runs were compared, and code R2 was determined to be the most optimal formulation. The improved dolutegravir-loaded Nano formulation offers an adequate release and may be appropriate for large-scale manufacturing with improved therapeutic outcome and patient compliance.
Sreethu K. Sreedharan and C. U. Amrutha *
Department of Pharmaceutics, Grace College of Pharmacy, Palakkad, Kerala, India.
16 March 2023
10 May 2023
31 May 2023
01 November 2023