Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CS
L
, medium CS
M
, high CS
H
molecular weights) and Labrasol
®
in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CS
M
and CS
H
; low cationic charge of CS
L
acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CS
L
increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CS
L
indicates that sustained release was achieved compared with ATR-L and Lipitor
®
. Anti-hyperlipidemic performance was pH dependent where ATR-CS
L
exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor
®
. Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CS
L
exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CS
L
as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.
Purpose: To develop and validate a novel reverse phase high performance liquid chromatographic (RP-HPLC) method for the quantification of atorvastatin in thermosensitive hydrogel
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