title: Development of Suppositories Containing Flutamide-Loaded Alginate-Tamarind Microparticles for Rectal Administration: In Vitro and in Vivo Studies.
abstract: In the present work the absorption of flutamide from suppositories containing hydrophilic tamarind alginate microparticles after rectal administration in rats was investigated with the purpose of enhancing bioavailability and to avoid hepatic toxicity. Microparticles were developed by ionic gelation method and optimized using one factorial design of response surface methodology. The optimized batch of microparticles had tamarind gum-sodium alginate (1 : 3) ratio and showed entrapment efficiency 94.969% and mucoadhesion strength 94.646% with desirability of 0.961. Suppositories loaded with microparticles were developed by fusion method using poloxamer 407 and poloxamer 188 in combination as suppository base. Kinetic analysis of the release data of microparticle-loaded suppositories showed time-independent release of drug. Higher values of 'n' (>0.89) represent Super Case II-type drug release. The pharmacokinetics of flutamide from flutamide tamarind alginate microparticle-loaded suppository were compared with oral suspension. Cmax of microparticle-loaded suppository was significantly larger than that of oral suspension (1.711 and 0.859 µg/mL, respectively).
authors.affiliation: Research Scholar, Department of Pharmaceutical Sciences, J.N.T. University.
authors.forename: Bharati Shivajirao
authors.initials: BS
authors.lastname: Patil
authors.forename: Hitendra Shaligram
authors.initials: HS
authors.lastname: Mahajan
authors.forename: Sanjay Javerilal
authors.initials: SJ
authors.lastname: Surana
mesh_terms: D000285:Administration, Rectal; D000464:Alginates / Q000737:chemistry*; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D005485:Flutamide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007700:Kinetics; D008297:Male; D020442:Poloxamer / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D013488:Suppositories; D029861:Tamarindus / Q000737:chemistry*
chemical_list: D000464:Alginates; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D006603:Hexuronic Acids; D013488:Suppositories; D020442:Poloxamer; D005485:Flutamide; D020723:Glucuronic Acid