title: Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: in vitro, ex vivo, and in vivo characterization.
abstract: The purpose of the present research was to develop bioadhesive buccal tablets for Felodipine (FDP) and Pioglitazone (PIO), low bioavailability drugs, in a combined dosage form for the management of diabetes and hypertension. Buccal tablets were prepared by direct compression method using bioadhesive polymers hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, and carbopol, alone or in combination of two polymers, and were evaluated for physicochemical properties, swelling index, in vitro bioadhesion, in vivo residence time, in vitro drug release, and ex vivo permeation through porcine buccal membrane. Formulation (PF6) showed peak detachment force (3.12 N), work of adhesion (0.72 mJ), swelling index (196%), erosion (10.8%), in vivo residence time of 280 min, in vitro drug release (99.65% and 98.96% in 6 h for FDP and PIO, respectively) with higuchi model release profile and permeated 66.1 and 64.6 % with a flux of 0.118 and 0.331 mg/h/cm(2) of FDP and PIO through porcine buccal membrane. The bioavailability study for optimized formulation (PF6) in pigs showed 2.05- and 2.13-times statistically significant (p < 0.05) improvement in bioavailability for FDP and PIO, respectively, after administration of buccal tablets compared to oral suspension. The ex vivo-in vivo correlation was found to have a biphasic pattern and followed type A correlation. The stability of the PF6 was studied and no significant changes were detected in drug content and in vitro release and ex vivo permeation through porcine buccal membrane after 6 months.
authors.affiliation: National Facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) Centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India.
authors.forename: Chinna Reddy
authors.initials: CR
authors.lastname: Palem
authors.forename: Ramesh
authors.initials: R
authors.lastname: Gannu
authors.forename: Shravan Kumar
authors.initials: SK
authors.lastname: Yamsani
authors.forename: Vamshi Vishnu
authors.initials: VV
authors.lastname: Yamsani
authors.forename: Madhusudan Rao
authors.initials: MR
authors.lastname: Yamsani
mesh_terms: D000180:Acrylic Resins; D000268:Adhesiveness; D000278:Administration, Buccal; D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D004338:Drug Combinations; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D015736:Felodipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D010539:Permeability; D000077205:Pioglitazone; D011145:Polyvinyls / Q000737:chemistry; D013045:Species Specificity; D013552:Swine; D013607:Tablets; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000180:Acrylic Resins; D000959:Antihypertensive Agents; D004338:Drug Combinations; D005079:Excipients; D007004:Hypoglycemic Agents; D011145:Polyvinyls; D013607:Tablets; D045162:Thiazolidinediones; C006912:carboxypolymethylene; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium; D015736:Felodipine; D000077205:Pioglitazone