title: Lyophilization monophase solution technique for improvement of the physicochemical properties of an anticancer drug, flutamide.
abstract: Flutamide (FLT), an anticancer drug for prostatic carcinoma, has poor aqueous solubility and low oral bioavailability. This study describes the ability of beta-cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) to form complexes with flutamide with enhanced solubility and dissolution rate in vitro. FLT-CD lyophilized dispersions (LDs) were prepared via lyophilization monophase solution technique using tertiary butyl alcohol (TBA) as a cosolvent. FLT showed an A(L)-type phase solubility diagram consistent with a linear increase in drug solubility as a function of CD concentration. Gas chromatography indicated that the LDs contain 0.02-0.03% w/w residual TBA. Based on the data from differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), FLT was fully amorphous in 1:5 FLT-HPbetaCD LD as indicated by complete disappearance of FLT endothermic and diffraction peaks. The Fourier transform infrared (FTIR) spectra indicated that a FLT-CD interaction took place in the lyophilized complex. The particle sizes of 1:1 FLT-betaCD and FLT-HPbetaCD LDs were 0.92 and 0.82microm, with a high surface area (484.55 and 705.68m(2)/g) and porosity (769.46 and 1020.99e(-3)ml/g), respectively. The dissolution rate of FLT from its CD complexes was enhanced significantly. After 30min in 0.1N HCl, about 73% and 86% of FLT were dissolved from 1:5 FLT-betaCD and FLT-HPbetaCD LDs, respectively, compared to only 13.45% of pure drug. No endothermic peak corresponding to FLT melting was detected in 1:5 FLT-HPbetaCD LD after storage at 20 degrees C and 45% relative humidity for 90days thus indicating the stability of this binary system. These data suggest that cyclodextrins might be useful adjuncts in preparation of immediate-release formulations of FLT.
authors: Department of Industrial Pharmacy, University of Alexandria, Alexandria, Egypt.
authors: Nazik
authors: N
authors: Elgindy
authors: Kadria
authors: K
authors: Elkhodairy
authors: Abdallah
authors: A
authors: Molokhia
authors: Ahmed
authors: A
authors: Elzoghby
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000970:Antineoplastic Agents / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005485:Flutamide / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods*; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D019999:Pharmaceutical Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005485:Flutamide