Rheological characterization of bioadhesive, antimicrobial, semisolids designed for the treatment of periodontal diseases: transient and dynamic viscoelastic and continuous shear analysis.
This study examined the creep behavior and oscillatory and flow properties of tetracycline-containing, bioadhesive semisolid formulations, designed for localized treatment of periodontal disease. Formulations were prepared containing hydroxyethylcellulose (HEC, 1, 3, or 5% w/w), poly(vinylpyrrolidone) (PVP, 2 or 3% w/w), polycarbophil (PC, 1 or 3% w/w), and tetracycline (5% w/w, as the hydrochloride). In creep analysis, each formulation exhibited several distinct regions that were mathematically modelled using a multi-element Voigt model with a residual spring and dashpot. Increasing the concentrations of each polymeric component decreased the elastic compliance (J(0)) yet increased the residual viscosity. In oscillatory analysis, increased polymer concentrations increased the storage modulus (G'), the loss modulus (G") and the dynamic viscosity (eta'), yet decreased the loss tangent (tan delta). The relationships between G' or G" and frequency were observed to plateau at higher frequencies, which is indicative of polymer chain entanglement and network formation. With the exception of formulations containing 1% HEC, the formulations were elastic (tan delta < 1), with large G' and small J(0) values. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymeric component increased the zero-shear viscosity (determined using the Cross model) and was further evidence of polymer chain entanglement. Formulations containing 1% w/w HEC possessed excellent flow properties, however, their thixotropic behavior and essentially elastoviscous nature (large J(0) and tan delta) would be disadvantageous for use in the treatment of periodontal disease because of rapid removal from the pocket and relatively uncontrolled drug release. Despite their advantageous viscoelastic properties, the flow properties of formulations containing 5% w/w HEC were inappropriate, rendering administration through a periodontal syringe potentially difficult. Based on their rheological behavior, formulations containing HEC (3% w/w), PVP (2 or 3% w/w), and PC (1 or 3% w/w) would be suitable for clinical application. However, consideration of other physicochemical properties (e.g., bioadhesion, drug release kinetics) must be performed prior to selection of the most suitable formulation for clinical examination. This study has highlighted the successful complimentary application of creep analysis and oscillatory and flow rheometry for the characterization and development of bioadhesive semisolid formulations for the treatment of periodontal disease.[1]References
- Rheological characterization of bioadhesive, antimicrobial, semisolids designed for the treatment of periodontal diseases: transient and dynamic viscoelastic and continuous shear analysis. Jones, D.S., Brown, A.F., Woolfson, A.D. Journal of pharmaceutical sciences. (2001) [Pubmed]
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