title: Development, optimization and in vivo characterization of domperidone-controlled release hot-melt-extruded films for buccal delivery.
abstract: OBJECTIVE
  The aim of the present investigation was the development and in vivo characterization of domperidone (DOM) hot-melt extruded (HME) controlled release films by central composite design (CCD) for buccal delivery.
  
  
  METHODS
  Concentration of PEO N750 (X1) and HPMC E5 LV (X2) as independent variables and tensile strength (Y1), percent drug release at 6 h (Q6, Y2) and percent drug permeated at 6 h (Y3, P6) as responses. In total, 13 formulations were prepared and studied. HME films were evaluated for drug excipient compatibility, physico-mechanical properties, drug content, in vitro drug release, bioadhesion, swelling and erosion, ex vivo permeation. Furthermore, statistically optimized formulation was subjected for bioavailability studies in healthy human volunteers.
  
  
  RESULTS
  Statistically optimized formulation exhibited a tensile strength (3.86 kg/mm(2)), 93.62 ± 2.84% of drug release and 63.36 ± 2.12% of drug permeated in 6 h. HME films demonstrated no drug excipient interaction and excellent content uniformity. Furthermore, optimized formulation exhibited elongation at break (38.6% mm(2)), peak detachment force (1.75 N), work of adhesion (3.21 mJ), swelling index (240.4%) and erosion (8.5%). Bioavailability from the statistically optimized buccal films was 3.2 times higher than the oral dosage form (p < 0.05). The ex vivo-in vivo correlation was found to have biphasic pattern and followed type A correlation. The stability of the optimized formulation was studied and no significant changes were detected in 6 months.
  
  
  CONCLUSIONS
  The results indicate that hot-melt extrusion is a viable technique for the preparation of DOM buccal-adhesive controlled release films with improved bioavailability by CCD.
authors.affiliation: a National Facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) Centre, University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Telangana , India and.
authors.forename: Chinna Reddy
authors.initials: CR
authors.lastname: Palem
authors.affiliation: a National Facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) Centre, University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Telangana , India and.
authors.forename: Narendar Reddy
authors.initials: NR
authors.lastname: Dudhipala
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, the University of Mississippi , University , MS , USA.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Battu
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, the University of Mississippi , University , MS , USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
authors.affiliation: a National Facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) Centre, University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Telangana , India and.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Rao Yamsani
mesh_terms: D000278:Administration, Buccal; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004294:Domperidone / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D013552:Swine; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D004294:Domperidone
keywords: Bioadhesion; EVIV correlation; central composite design; controlled release; domperidone; ex vivo permeation; hot-melt extrusion; in vitro dissolution