title: Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease.
abstract: This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.
authors.affiliation: School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.jones@qub.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Lawlor
authors.forename: A David
authors.initials: AD
authors.lastname: Woolfson
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients; D008298:Maleates / Q000737:chemistry*; D010510:Periodontal Diseases / Q000188:drug therapy*; D010592:Pharmaceutic Aids; D011095:Polyethylenes / Q000737:chemistry*; D011108:Polymers; D011205:Povidone / Q000737:chemistry*; D012212:Rheology; D013752:Tetracycline / Q000008:administration & dosage* / Q000627:therapeutic use*; D014014:Tissue Adhesives; D014783:Viscosity
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D008298:Maleates; D010592:Pharmaceutic Aids; D011095:Polyethylenes; D011108:Polymers; D014014:Tissue Adhesives; C043105:poly(methyl vinyl ether-co-maleic anhydride); D013752:Tetracycline; D011205:Povidone