Jin Wang1, Binbin Huang1, Jie Dai1, Guoguang Chen1, Lili Ren1,2. 1. School of Pharmacy, Nanjing Tech University 5th Mofan Road, Nanjing 210009, Jiangsu, China. 2. Department of Microbiology and Immunology, Stanford University Stanford, CA 94305, USA.
Abstract
OBJECTIVES: This study aimed to improve the solubility in water and bioavailability in vivo of lurasidone hydrochloride (LUR). METHODS: The saturated aqueous solution method was used to prepare an inclusion complex of LUR with sulfobutylether-β-cyclodextrin, or SBE-β-CD (LUR-SBE-β-CD). A single-factor test was used for the preliminary screening of important preparing conditions including the ethanol concentration, the SBE-β-CD concentration, temperature, and pH. Then central composite design response surface methodology (CCD) was adopted for the optimum craft. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD) were used to confirm the formation of LUR-SBE-β-CD. The in vitro release profiles of LUR-SBE-β-CD were determined at different pHs and in simulated gastrointestinal fluid. RESULTS: The dissolution studies revealed that the dissolution of LUR in LUR-SBE-β-CD was much improved in the four media and simulated gastrointestinal fluid. Similar profiles of LUR-SBE-β-CD were obtained in pharmacokinetic studies whether beagle dogs took food or not. CONCLUSIONS: The bioavailability of LUR can be improved and the food effect can be eliminated by LUR-SBE-β-CD. AJTR
OBJECTIVES: This study aimed to improve the solubility in water and bioavailability in vivo of lurasidone hydrochloride (LUR). METHODS: The saturated aqueous solution method was used to prepare an inclusion complex of LUR with sulfobutylether-β-cyclodextrin, or SBE-β-CD (LUR-SBE-β-CD). A single-factor test was used for the preliminary screening of important preparing conditions including the ethanol concentration, the SBE-β-CD concentration, temperature, and pH. Then central composite design response surface methodology (CCD) was adopted for the optimum craft. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD) were used to confirm the formation of LUR-SBE-β-CD. The in vitro release profiles of LUR-SBE-β-CD were determined at different pHs and in simulated gastrointestinal fluid. RESULTS: The dissolution studies revealed that the dissolution of LUR in LUR-SBE-β-CD was much improved in the four media and simulated gastrointestinal fluid. Similar profiles of LUR-SBE-β-CD were obtained in pharmacokinetic studies whether beagle dogs took food or not. CONCLUSIONS: The bioavailability of LUR can be improved and the food effect can be eliminated by LUR-SBE-β-CD. AJTR
Authors: E A Luna; E R Bornancini; R J Tait; D O Thompson; J F Stobaugh; R A Rajewski; V J Stella Journal: J Pharm Biomed Anal Date: 1996-10 Impact factor: 3.935