The objective was to develop chitosan atorvastatin (ATR) nanocrystals loaded into Poly
(lactic-co-glycolic) acid (PLGA) injectable in situ gel (ISG) system that can minimize initial drug burst
and enhance hypolipidemic effect. ATR nanocrystals were successfully characterized for size, morphology,
crystallinity and drug-excipients interaction. The effects of varied polymer concentration and
gelling solvents were evaluated for initial burst release and in vivo efficacy. Short term stability study was also conducted
for the promising formulation. Nanocrystals of size 254 nm were prepared using low molecular weight chitosan and were
of smooth surface with multiple scaffolds like structures. X-ray powder diffraction revealed the crystalline structure of the
prepared nanocrystals while no drug-excipients interactions were observed. Addition of nanocrystals did not significantly
alter gelation property of the ISG system that showed acceptable syringeability. The promising ISG formulation was
achieved with 45% PLGA in N-methyl pyrrolidone: benzyl benzoate (1:3). In-vitro dissolution study illustrated lower initial
ATR burst and prolonged drug release from nanocrystal based ISG when compared to plain ATR ISG. The pharmacokinetic
and hypolipidemic biochemical parameters were comparable in the two formulations. The promising formulation
exhibited minimum drug degradation at 4 °C and so could be considered as an ideal ISG delivery system.
Keywords: Atorvastatin, nanocrystals, PLGA, in-situ gel, hypolipidemic efficacy.
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