Catanionic Aggregates in Gels : Prolonged Drug Release and Potential Implications for Topical Use

Abstract: Gels are popular dosage forms.  This topical dosage form may be advantageous compared to oral or parenteral dosage forms. Favorable rheological or bioadhesive properties of gels might provide extended contact times at the site of administration compared to aqueous solutions. However, due to the high water content of gels, these are usually quickly emptied of the drug substance. One way of prolonging the drug release from gels is to contain the drug substance in catanionic aggregates in the gel. These aggregates are formed in solutions of oppositely charged surfactants and a drug can be used instead of one of the surfactants.   In this thesis catanionic aggregates composed of drug substances and oppositely charged surfactants were studied and the possibility to use these aggregates for the purpose of prolonged drug release was investigated. The formation of catanionic aggregates when using drugs was found to be a common occurrence in addition to which, the oppositely charged surfactant can be varied and surfactants of natural origin with a low toxicity were used. Most combinations tested rendered either vesicles or elongated micelles. When the catanionic aggregates were contained in gels the drug release was substantially prolonged. The apparent diffusion coefficients were lowered 10-100 times compared to the reference gels. When gels with catanionic vesicles with substantial prolonged drug release were applied to skin the penetration rate was lowered extensively. No morphological differences were observed between skin samples that had been exposed to formulations containing catanionic aggregates and skin samples exposed to saline solution, air or formulations containing only the drug. Both conventional, covalently linked pre-formed gels and physical gels, where the catanionic vesicles form the cross-links upon interaction with the polymer, can be used for these purposes. When the effect of drug release on aggregate structure was studied, it was shown that vesicles are present in both conventional and physical gels throughout the drug release process.   This thesis shows that catanionic aggregates contained in gels can present an advantageous formulation strategy to prolong the drug release, thereby improving the efficiency of gel formulations.