title: Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability.
abstract: The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too.
authors.affiliation: Department of Pharmaceutics, Hamdard University , New Delhi , India .
authors.forename: Naushad
authors.initials: N
authors.lastname: Alam
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rizwan
authors.forename: Akifa
authors.initials: A
authors.lastname: Ahmad
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.forename: Mohammad
authors.initials: M
authors.lastname: Aqil
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D009997:Osmotic Pressure; D011817:Rabbits; D015203:Reproducibility of Results; D013499:Surface Properties; D013607:Tablets; D014292:Trimetazidine / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D014665:Vasodilator Agents; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; D002482:Cellulose; D014292:Trimetazidine
keywords: Absorption; bioadhesion; controlled release; in vitro drug release; osmotic pump