Physicochemical characterization and preliminary in vivo efficacy of bioadhesive, semisolid formulations containing flurbiprofen for the treatment of gingivitis

• Published in: Journal of pharmaceutical sciences Vol. 88; no. 6; p. 592
• Main Authors: Jones, D S, Irwin, C R, Woolfson, A D, Djokic, J, Adams, V
• Format: Journal Article
• Language: English
• Published: United States 01-06-1999
• Subjects: Acrylic Resins - administration & dosage; Acrylic Resins - chemistry; Adhesiveness; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Cellulose - administration & dosage; Cellulose - analogs & derivatives; Cellulose - chemistry; Compressive Strength; Delayed-Action Preparations; Double-Blind Method; Drug Carriers; Flurbiprofen - administration & dosage; Flurbiprofen - chemistry; Gels - administration & dosage; Gels - chemistry; Gingivitis - drug therapy; Hardness; Humans; Pharmaceutic Aids - administration & dosage; Pharmaceutic Aids - chemistry; Povidone - administration & dosage; Povidone - chemistry
• ISSN: 0022-3549
• DOI: 10.1021/js9803095

In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w), poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t10%, t30%) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t10%, t30% due to excessive swelling (and disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) or 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accumulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.