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1% (w/v) aqueous solutions of tropicamide (TR), a poorly water-soluble mydriatic-cycloplegic drug, are usually obtained by adjusting the pH to approximately 5.0, at the expense, however, of ocular tolerance and bioavailability. The capacity of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to solubilize TR in pH 7.4 0.02 M phosphate buffer was investigated in the absence and presence of hydrophilic polymers (PVP, CMC and HPMC). Approximately 3.5% (w/v) HP-beta-CD was required to solubilize 1% (w/v) TR in pH 7.4 buffer at room temperature. The required amount was reduced to 0.9% (w/v) by heating at 120 degrees C in the presence of 0.1% (w/v) HPMC. Mydriatic activity tests in rabbits showed an improved bioavailability and maximal mydriatic response for two CD formulations, with and without HPMC, when compared to standard 1% (w/v) TR eyedrops, buffered at pH 5.0. The improved in vivo behaviour of the CD formulations are likely due to their physiological pH, resulting in a reduced irritant effect, although an effect of HP-beta-CD on corneal permeability cannot be dismissed a priori.

Systematic investigations on the diffusion of ibuprofen (IBU) from supersaturated solutions through human epidermis are reported. Significant flux enhancement was obtained from supersaturated solutions compared to the saturated solution. Hydroxypropyl methylcellulose (HPMC), when used as an additive was found to be effective in maintaining the high activity state at high degrees of saturation (DS). The increase in the flux was proportional to the DS. In the presence of 2-hydroxypropyl-beta-cyclodextrin (CD) at DS 2 and 3 a lower flux was observed compared to HPMC. At DS 5 a higher flux enhancement was found suggesting that CD might act as a penetration enhancer at certain CD/drug ratios. Studies on the mechanism of stabilisation of HPMC and CD on IBU crystallisation from supersaturated systems showed that HPMC acts as a growth inhibitor and habit modifier whereas CD does not influence the crystallisation process.

Permeation enhancement of ibuprofen from supersaturated solutions formed using the cosolvent technique was investigated using silicone as a model membrane. Hydroxpropyl methyl cellulose and hydroxpropyl-beta-cyclodextrin were used to stabilise the supersaturated states. Physical stability studies showed best results for low drug concentrations in a 40:60 propylene glycol/water cosolvent system. Variations in flux across model silicone membranes from saturated solutions were observed as the PG content was increased. The flux of IBU increased with the degree of saturation for solutions prepared in a 40:60 PG/water cosolvent mixture. HPMC and CD were found to be effective in enhancing the stability of supersaturated solutions of IBU. The mechanisms of action are different for the two additives and are discussed.