Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Preparation and Pharmacokinetics in Rats of Celecoxib Nanosuspension / 中国药师

Objective:To prepare celecoxib nanosuspension ( CXB-NSs) and study the pharmacokinetics of CXB-NSs in rats. Methods:CXB-NSs were prepared by an anti-solvent precipitation and high pressure homogenization method. The particle size, polydispersion index ( PdI) and zeta potential of the nanosuspension were studied. Totally 12 Wistar rats were randomly divided into CXB-NSs group and CXB suspension group, and gastric drug dose was 100 mg·kg-1 . CXB concentration in plasma was determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, polydispersion index, zeta potential of CXB-NSs was (442. 5 ± 61. 9) nm, 0. 312 ± 0. 057 and ( -31. 6 ± 3. 9) mV, respectively. AUC (0-t) of CXB suspension and CXB-NSs was (5.13 ±0.77) and (13.51 ±3.18) mg·L-1·h, half time (t1/2) was (12.31 ±1.91) and (12.73 ±1.83) h, Tmax was (2. 48 ± 0. 37) and (1. 41 ± 0. 27) h and Cmax was (0. 94 ± 0. 31) and (2. 38 ± 0. 25) mg·L-1 , respectively. Conclusion:CXB-NSs can remarkably increase bioavailability in rats.