PubMed · 12008804
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Steve Armstrong. 2002. Dentin bonding.. https://doi.org/10.1111/j.1708-8240.2002.tb00154.x
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Mucoadhesive patches containing 10mg miconazole nitrate were evaluated. The patches were prepared with ionic polymers, sodium carboxymethyl cellulose (SCMC) and chitosan, or non-ionic polymers, polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC) and hydroxypropylmethyl cellulose (HPMC). Convenient bioadhesion, acceptable elasticity, swelling and surface pH were obtained. Patches exhibited sustained release over more than 5h and the addition of polyvinyl pyrrolidone (PVP) generally enhanced the release rate. Optimum release behaviour was shown with patches containing 10% w/v PVA and 5% w/v PVP. Study of the in vivo release from this formulation revealed uniform and effective salivary levels with adequate comfort and compliance during at least 6h. On the contrary, in vivo release of the commercial oral gel product resulted in a burst and transient release of miconazole, which diminished sharply after the first hour of application. Storage of these patches for 6 months did not affect the elastic properties, however, enhanced release rates were observed due to marked changes in the crystal habit of the drug.
The aim of this study was to improve the properties of chitosan as excipient in drug delivery systems by the covalent attachment of thiol moieties. This was achieved by the modification of chitosan with 2-iminothiolane. The resulting chitosan-4-thio-butyl-amidine conjugates (chitosan-TBA conjugates) displayed up to 408.9+/-49.8 micromol thiol groups per gram polymer. Because of the formation of disulfide bonds based on an oxidation process of the immobilized thiol groups under physiological conditions, chitosan-TBA conjugates exhibit in situ gelling properties. After less than 2h, 1.5% (m/v) chitosan-TBA conjugate solutions of pH 5.5 formed covalently cross-linked gels. The viscosity increased in positive correlation with the amount of thiol groups immobilized on chitosan. In addition, also the mucoadhesive properties were strongly improved by the covalent attachment of thiol groups on chitosan. The adhesion time of tablets based on the unmodified polymer on freshly excised porcine intestinal mucosa spanned on a rotating cylinder in an artificial intestinal fluid was extended more than 140-fold by using the thiolated version. Drug release studies out of tablets comprising the chitosan-TBA conjugate demonstrated that an almost zero-order release kinetic was achieved for the model drug clotrimazole within the first 6h. The modification of chitosan with 2-iminothiolane leads, therefore to thiolated polymers, which represent a promising tool for the development of in situ gelling and/or mucoadhesive drug delivery systems.
This study was performed to develop new enhanced anesthetic benzocaine gels with a suitable bioadhesive property for local anesthetic effects. As the concentration of benzocaine in the HPMC gels increased up to 15%, the permeation of drug increased, thereafter slightly increased. The activation energy of drug permeation was 11.29 kcal/mol. Bioadhesive forces were also measured. The permeation rate of drug through the skin was studied using various enhancers, such as glycols, non-ionic surfactants or fatty acids. Among the enhancers used, diethylene glycol showed the most enhancing effects. Analgesic activity was examined using a tail-flick analgesimeter. According to the rat tail-flick test, the value of AUEC (0 - 360min) of 15% benzocaine gels containing diethylene glycol was 4662 +/- 200 s min, while that of gels without diethylene glycol was 3353 +/- 132 s min, showing about 1.39-fold increase in analgesic activity. Fifteen percentage of benzocaine gels containing diethylene glycol showed the most enhanced, prolonged analgesic effects, showing the maximum anesthetic effects at 240 min, while the gels without diethylene glycol showed maximum effect at 180 min.