title: Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment.
abstract: BACKGROUND
  Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis.
  
  
  OBJECTIVE
  Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application.
  
  
  METHODS
  Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects.
  
  
  RESULTS
  Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12 h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the -NH groups of metformin and -OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment.
  
  
  CONCLUSIONS
  The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.
authors: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , Princess Nourah bint Abdulrahman University , Riyadh , Saudi Arabia.|b Department of Pharmaceutics, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
authors: Abeer Ahmed
authors: AA
authors: Kassem
authors: c Department of Pharmaceutical Sciences, Faculty of Pharmacy , Beirut Arab University , Beirut , Lebanon.|d Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
authors: Doaa Ahmed Elsayed
authors: DA
authors: Issa
authors: e Department of Oral Medicine, Periodontology, Oral Diagnosis and Radiology, Faculty of Dentistry , Alexandria University , Alexandria , Egypt.
authors: Gehan Sherif
authors: GS
authors: Kotry
authors: f Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing , Pharos University in Alexandria , Alexandria , Egypt.
authors: Ragwa Mohamed
authors: RM
authors: Farid
mesh_terms: D000328:Adult; D000464:Alginates / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry; D003738:Dental Cements / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000737:chemistry; D008875:Middle Aged; D010514:Periodontal Pocket / Q000175:diagnosis / Q000188:drug therapy*; D010518:Periodontitis / Q000175:diagnosis / Q000188:drug therapy; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine; D013873:Thionucleotides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D003738:Dental Cements; D006603:Hexuronic Acids; D013438:Sulfhydryl Compounds; D013873:Thionucleotides; D020723:Glucuronic Acid; D008687:Metformin
keywords: Metformin; controlled release; multiple-layer film; periodontitis; thiolated alginate