Viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solids for topical application to the oropharynx.
OBJECTIVE
This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx.


METHODS
Oscillatory rheometry was performed using a Carri-Med CSL2-100 rheometer at 20.0 +/- 0.1 degrees C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 x 10(-3) rad) and defined viscoelastic parameters, namely storage modulus (G'), loss modulus (G"), loss tangent (tan delta) and dynamic viscosity (eta'), measured over a defined frequency range (0.01-1.0 Hz).


RESULTS
As the oscillatory frequency was increased, G' G" of all formulations increased, whereas both eta' and tan delta significantly decreased. The magnitude of increase of G' and G" as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G', G", eta' yet decreased tan delta, observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan delta decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient "free-water" was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation eta' increased due to the attendant effects of polymer chain entanglement and polymer state on overall formulation viscosity.


CONCLUSIONS
Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.
Jones
D S
DS
The Pharmaceutical Sciences Group, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, Northern Ireland, United Kingdom. d.jones@qub.ac.uk
Woolfson
A D
AD
Brown
A F
AF
D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D000269:Adhesives / Q000737:chemistry; D000287:Administration, Topical; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002710:Chlorhexidine / Q000008:administration & dosage / Q000737:chemistry*; D004548:Elasticity; D009960:Oropharynx; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011205:Povidone / Q000008:administration & dosage / Q000737:chemistry; D014783:Viscosity
D000180:Acrylic Resins; D000269:Adhesives; D000891:Anti-Infective Agents, Local; D001672:Biocompatible Materials; D011108:Polymers; C030312:calcium polycarbophil; D002482:Cellulose; C002283:hydroxyethylcellulose; D011205:Povidone; D002710:Chlorhexidine