title: Construction and in vitro characterization of an optimized porosity-enabled amalgamated matrix for sustained transbuccal drug delivery.
abstract: This research focused on constructing and characterizing an optimized porosity-enabled amalgamated matrix (P-EAM) for sustained transbuccal drug delivery. An interphase, co-particulate, co-solvent, homogenization technique and lyophilization guided through a Box-Behnken experimental design was employed in the fabrication, characterization and optimization of 15 P-EAMs. The effects of varying factor levels on the characteristic in vitro physicochemical performances of the P-EAMs were explored. Formulations had an average weight of 128.44+/-3.48 mg with a dimensional size of 8mm by 5mm. Surface morphology showed varieties of pore structures, widespread distributions and uneven interconnectors. Satisfactory drug-loading was achieved (53.14+/-2.19-99.02+/-0.74%). Overall amount of drug released in 8h was measured by the MDT(50%) value which ranged between 22.50 and 225.00 min. Formulation demonstrated significant levels of ex vivo bioadhesive strength measured as detachment force (F(det)=0.964+/-0.015 to 1.042+/-0.025 N) and work of adhesion (omega(adh)=0.0014+/-0.00005 to 0.0028+/-0.00008 J). The potential of the P-EAMs to initiate and sustain ex vivo transbuccal permeation of drug was shown and measured as a cumulative value of between 25.02+/-0.85 and 82.21+/-0.57% in 8h. Formulations were mesoporous in nature with pore sizes ranging from 40 to 100 A characterized by the presence of interconnectors. Statistical constraints were simultaneously set to obtain levels of independent variables that optimized the P-EAM formulation.
authors.affiliation: Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
authors.forename: Oluwatoyin A
authors.initials: OA
authors.lastname: Adeleke
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
mesh_terms: D000269:Adhesives / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000278:Administration, Buccal; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D044367:Phase Transition; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016062:Porosity; D012212:Rheology; D013499:Surface Properties; D013552:Swine
chemical_list: D000269:Adhesives; D004337:Drug Carriers; D010672:Phenytoin