title: In vitro, ex vivo and in silico mechanistic elucidation of the performance of an optimized porosity-controlled multi-elemental transbuccal system.
abstract: OBJECTIVE
  To elucidate the mechanisms of construction and performance of a porosity controlled, multi-elemental transbuccal system employing experimental and computational approaches.
  
  
  METHODS
  The production of the formulation was guided through a Box-Benkhen design employing homogenization coupled with lyophilization. The physicochemical and physicomechanical properties of the experimental design formulations were quantified with relevant analytical techniques. The influence of changes in porosity measures on the magnitude of these physical properties were explored mathematically. Furthermore, experimental outputs from the Box-Behnken design formulations were fitted into set limits and optimized using the response surface method. The optimized porosity-controlled formulation was subjected to mechanistic experimental and computational elucidations.
  
  
  RESULTS
  In general, the changes in magnitudes of studied porosity quantities had significant impact on formulation physicochemical and physicomechanical properties. The generation of an optimized formulation validated the stability and accuracy of the Box-Behnken experimental design. Experimental investigations revealed that the construction of this formulation is as a result of non-destructive physical interactions amongst its make-up compounds while its mechanism of performance is anchored mainly upon a gradual collapse of its ordered porous structure. Furthermore, the molecule mechanics simulations quantitatively predicted the molecular interactions inherent to multicomponent matrix formation and the mucoadhesion mechanism.
  
  
  CONCLUSIONS
  The fabrication and performance mechanisms of the porosity-controlled transbuccal system was successfully explored.
authors: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutics, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
authors: Oluwatoyin A
authors: OA
authors: Adeleke
authors: Yahya E
authors: YE
authors: Choonara
authors: Lisa C
authors: LC
authors: du Toit
authors: Pradeep
authors: P
authors: Kumar
authors: Viness
authors: V
authors: Pillay
mesh_terms: D000268:Adhesiveness; D000278:Administration, Buccal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005612:Freeze Drying; D066298:In Vitro Techniques; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism*; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016062:Porosity; D012212:Rheology; D013552:Swine
chemical_list: D004337:Drug Carriers; D010672:Phenytoin
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