The aim of the present work was to extend our previous in-vitro drug release studies using semisolid dermatological bases with non-impregnated cellulose acetate membranes. A comparison of the performances of two apparatuses, the more commonly used Franz cell and the new modified USP (mini paddle with ointment holding cell) systems were applied to this work. Five different semisolid as well as two marketed preparations containing 1% diclofenac sodium were used. Complex, slightly non-linear release curves indicating sink conditions were found. This was explained by the co-diffusion of excipients modifying the characteristics of the membrane and the receiving medium dynamically. Although our test model is, as a rule, not suitable to establish an in-vivo-in-vitro correlation, good qualitative as well as quantitative correlations were found within some types of dermatological bases. The correlation between the results of the two in-vitro methods also depends on the type of semisolids studied. The release curve characteristics and the amount of diclofenac sodium released at 6 h were measured. Their repeatability and reproducibility were calculated. The slopes and Q-values were correlated with in-vivo data. In general, the modified USP method provided more precise results than the Franz cell method.

Semisolid products are 8-10% of dosage forms, but -in contrast with the solid dosage forms -we do not have any validated method for their drug release in any Pharmacopoeia. Kinetics of release process and its critical factors in case of 1% diclofenac sodium containing hydrogel, organogel, gelemulsion, o/w and w/o creams were observed under in vitro conditions. Comparison of results between Franz diffusion cell and paddle over disk method was made using synthetic cellulose acetate membrane soaked in buffer solution or in isopropyl myristate. In vivo studies were carried out on male Wistar rats; the carrageenan paw edema decreasing effect of 12 different formulations was measured in comparison with a control group. All products reduced paw edema in rats, although we found significant differences among them both in vitro and in vivo.

Semisolid systems (creams, gels etc.) for dermal application get more and more importance in pharmaceutical and cosmetic industry. However the number of methodologies for their physico-chemical characterization have been increasing; development of methods for the measurement of the active agent's release onto the skin surface is still a challenging task. Beside measuring the amount of the active agent reaching the skin; dissolution testing (also called release testing) can be also a good indicator of product composition changes, therefore it can be used as quality control methodology. The purpose of this study was to investigate the in vitro drug release of active agents from hydrogels, organogels, o/w and w/o creams, emulgels and w/o/w multiple emulsions for dermal use by means of the vertical diffusion cell methodology, for quality control purposes.

No abstract