STUDY OF IN-VITRO RELEASE OF CORTICOIDS IN TOPICAL FORMULATIONS

Two glucocorticoid drugs (betamethasone disodium phosphate, BMNaP, and betamethasone acetate, BMA) were incorporated into topical formulatio ns based on hydrogels of Aquacoat(TM) latex with either Carbopol 940 o r polyethylenglycol (PEG). The effects are analysed of the route of pr eparation, concentration of Aquacoat latex added, pH, and addition of plasticizers on the rate of release of drugs from the preparations. Ou r results demonstrate that drug solubility in the hydrogel is the esse ntial factor dominating release mechanisms. Thus, over 90% of the solu ble compound BMNaP is recovered from Carbopol systems 24 h after the b eginning of the experiment, regardless of preparation route, latex con centration or pH. When solubility-related mechanisms are not available (BMA is almost insoluble in water or aqueous solvents), some control on release rates is achieved: adsorption of the active compound on the latex particles and its subsequent desorption causes a slower rate of release the greater the latex concentration (up to similar to 30%). S onication of drug + latex systems seems to slow down release mechanism s, probably due to improved adsorption of BMA on the polymer particles . No significant effect of pH is observed on BMA release, suggesting t hat BMA solubilization caused by pH increase (no pH's higher than 7 we re tested) cannot compensate for adsorption-desorption mechanisms domi nating the release of this drug. When the base of the preparation was PEG, almost 100% of either BMA or BMNaP was released shortly after pre paration of the systems, at whatever concentration of Aquacoat latex. The same behaviour was found when glycerin or propylenglycol were adde d as plasticizers. However, in PEG-based preparations containing eithe r citric acid or buthyl phtalate, release of corticoids, mainly BMA, c an be controlled to a large extent by changing the concentrations of a ny of such plasticizers.