Low-frequency dielectric spectroscopy as a tool for studying the compatibility between pharmaceutical gels and mucous tissue.

This interdisciplinary work demonstrates how low-frequency dielectric spectroscopy, a technique that is frequently used within physics, can be used to assess the possibilities of intimate surface contact between a polymer gel and mucous tissue, which is generally considered to be the first step in the mucoadhesion process. The dielectric responses of five different gels, of freshly excised porcine nasal mucosa and of systems made by combining the two were measured. All spectra were modeled by a Randles electric circuit containing a diffusion element, a barrier resistance in parallel with a capacitance, and a high-frequency resistance. The results were used to create a measure of the compatibility between the gel and the mucus, which we have named the compatibility factor. Thus, the compatibility factor provides us with a measure of the ease with which a charged species passes the interface between a gel and the mucus layer. The compatibility factor is calculated from the high frequency (kHz region) response of the gel, of the mucosa, and of the combined system. The two highest compatibility factors in this study were obtained for gels based on crosslinked poly(acrylic acid) and chitosan, which was in agreement with the results from mucoadhesion measurements that were performed using a tensile strength method.

[1]  P. Alexandridis,et al.  Effect of pharmaceutically acceptable glycols on the stability of the liquid crystalline gels formed by Poloxamer 407 in water. , 2002, Journal of colloid and interface science.

[2]  H. Hägerström,et al.  Interpretation of mucoadhesive properties of polymer gel preparations using a tensile strength method , 2001, The Journal of pharmacy and pharmacology.

[3]  L. Bromberg Enhanced nasal retention of hydrophobically modified polyelectrolytes , 2001, The Journal of pharmacy and pharmacology.

[4]  J. Carlfors,et al.  Rheological evaluation of Gelrite in situ gels for ophthalmic use. , 1998, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  Dahl,et al.  Anatomy, physiology and function of the nasal cavities in health and disease. , 1998, Advanced drug delivery reviews.

[6]  David S. Jones,et al.  Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers , 1997 .

[7]  M. Donovan,et al.  Intranasal mucociliary clearance of putative bioadhesive polymer gels , 1996 .

[8]  D. Craig,et al.  The Effects of Ageing on the Rheological, Dielectric and Mucoadhesive Properties of Poly(Acrylic Acid) Gel Systems , 1996, Pharmaceutical Research.

[9]  D. Craig,et al.  Dielectric Analysis of Pharmaceutical Systems , 1995 .

[10]  D. Craig,et al.  An investigation into the rheological, dielectric and mucoadhesive properties of poly(acrylic acid) gel systems , 1995 .

[11]  J. Newton,et al.  An investigation into the structure and properties of Carbopol 934 gels using dielectric spectroscopy and oscillatory rheometry , 1994 .

[12]  Robert Gurny,et al.  Gamma scintigraphic study of precorneal drainage and assessment of miotic response in rabbits of various ophthalmic formulations containing pilocarpine , 1993 .

[13]  Susi Burgalassi,et al.  Evaluation of muco-adhesive properties and in vivo activity of ophthalmic vehicles based on hyaluronic acid , 1989 .

[14]  Clive G. Wilson,et al.  The influence of solution viscosity on nasal spray deposition and clearance , 1988 .

[15]  R. Rowe,et al.  The characterization of heterogeneous gels by means of a dielectric technique: II. Formulation and structural considerations , 1988 .

[16]  R. Rowe,et al.  The characterization of heterogeneous gels by means of a dielectric technique: I. Theory and preliminary evaluation , 1987 .

[17]  Robert A. Huggins,et al.  Application of A-C Techniques to the Study of Lithium Diffusion in Tungsten Trioxide Thin Films , 1980 .

[18]  L. Illum BIOADHESIVE FORMULATIONS FOR NASAL PEPTIDE DELIVERY , 1999 .

[19]  Ramon Bragós,et al.  Electrical bioimpedance methods: applications to medicine and biotechnology , 1999 .

[20]  Javed Ali,et al.  Mucoadhesive Drug Delivery Systems , 1997 .

[21]  N. Peppas,et al.  Hydrogels as mucoadhesive and bioadhesive materials: a review. , 1996, Biomaterials.

[22]  J. Robinson,et al.  Oral cavity as a site for bioadhesive drug delivery , 1994 .

[23]  M. Lanza,et al.  Low-frequency dielectric investigations in polymer-like lecithin gels , 1993 .

[24]  J. Newton,et al.  Dielectric characterisation of sodium alginate gels , 1992 .

[25]  Nikolaos A. Peppas,et al.  Pharmaceutical and Medical Aspects of Bioadhesive Systems for Drug Administration , 1988 .

[26]  J. Randles Kinetics of rapid electrode reactions , 1947 .

[27]  E. Warburg,et al.  Ueber das Verhalten sogenannter unpolarisirbarer Elektroden gegen Wechselstrom , 1899 .