Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment ofperiodontal disease

This study describes the formulation, characterisation and preliminary clin ical evaluation of mucoadhesive, semi-solid formulations containing hydroxy ethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), poly carbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydroch loride). Each formulation was characterised in terms of drug release, hardn ess, compressibility, adhesiveness (using a texture analyser in texture pro file analysis mode), syringeability (using a texture analyser in compressio n mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formula tions ranged from 0.78+/-0.02 to 1.27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymer ic component significantly increased the time required for 10 and 30% relea se of the original mass of tetracycline, due to both increased viscosity an d, additionally, the unique swelling properties of the formulations. Increa sing concentrations of each polymeric component also increased the hardness , compressibility, adhesiveness, syringeability and mucoadhesion of the for mulations. The effects on product hardness, compressibility and syringeabil ity may be due to increased product viscosity and, hence, increased resista nce to compression. Similarly, the effects of these polymers on adhesivenes s/mucoadhesion highlight their mucoadhesive nature and, importantly, the ef fects of polymer state (particularly PC) on these properties. Thus, in form ulations where the neutralisation of PC was maximally suppressed, adhesiven ess and mucoadhesion were also maximal. Interestingly, statistical interact ions were primarily observed between the effects of HEC and PC on drug rele ase, mechanical and mucoadhesive properties. These were explained by the ef fects of HEC on the physical state of PC, namely swollen or unswollen. In t he preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% H EC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride) . The clinical efficacy of this (test) formulation was compared to an ident ical tetracycline-devoid (control) formulation in nine periodontal pockets (greater than or equal to 5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal h ealth as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechani cal plaque removal, the tetracycline-containing semi-solid systems describe d in this study would augment such therapy by enhancing the removal of path ogens, thus improving periodontal health. (C) 2000 Elsevier Science B.V. Al l rights reserved.