title: Lyophilization monophase solution technique for preparation of amorphous flutamide dispersions.
abstract: Flutamide (FLT) is a poorly soluble anticancer drug. Therefore, lyophilized dispersions (LDs) of FLT with polyvinylpyrrolidone (PVP) K30, polyethylene glycol (PEG) 6000, and pluronic F127 were prepared via lyophilization monophase solution technique with the aim of increasing its dissolution rate. FLT showed an A(L)-type phase solubility diagrams with PVP and PEG, whereas A(N)-type diagram was obtained with pluronic. The amount of residual tertiary butyl alcohol, determined by gas chromatography, was 0.015-0.021% w/w. Differential scanning calorimetry and X-ray diffractometry revealed that FLT-polymer 1:1 LDs were partially amorphous, whereas the 1:3 and 1:5 LDs were completely amorphous. After 6 months storage, polymers under study inhibited FLT recrystallization maintaining its amorphous form. The particle size of FLT-polymer LDs was between 0.81 and 2.13 μm, with a high surface area (268.43-510.82 m²/g) and porosity (354.01-676.23 e⁻³ mL/g). Also, the poor flow properties of FLT could be improved but to a limited extent. FLT dissolution was significantly enhanced with the fastest dissolution that was achieved using pluronic. After 30 min, about 66.52%, 78.23%, and 81.64% of FLT was dissolved from 1:5 FLT-PVP, PEG, and pluronic LDs, respectively, compared with only 13.45% of FLT. These data suggest that these polymers might be useful adjuncts in preparation and stabilization of amorphous immediate-release FLT LDs.
authors.affiliation: Department of Industrial Pharmacy, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
authors.forename: Nazik
authors.initials: N
authors.lastname: Elgindy
authors.forename: Kadria
authors.initials: K
authors.lastname: Elkhodairy
authors.forename: Abdallah
authors.initials: A
authors.lastname: Molokhia
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elzoghby
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005485:Flutamide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005612:Freeze Drying; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010316:Particle Size; D020442:Poloxamer; D011092:Polyethylene Glycols; D011205:Povidone; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012995:Solubility; D012996:Solutions
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D012996:Solutions; D020442:Poloxamer; D011092:Polyethylene Glycols; D005485:Flutamide; D011205:Povidone