PHYSICOCHEMICAL ASPECTS OF DRUG RELEASE .14. THE EFFECTS OF SOME IONIC AND NONIONIC SURFACTANTS ON PROPERTIES OF A SPARINGLY SOLUBLE DRUG IN SOLID DISPERSIONS

The nonionic surfactants polysorbate 80 and polyethylene dodecyl ether (Brij 35), the anionic surfactant sodium dodecyl sulphate (SDS) and the cationic surfactant, dodecyltrimethylammonium bromide (DTAB) were incorporated in dispersions of 10% w/w griseofulvin with PEG 3000 as a carrier. An almost instant and complete dissolution was obtained for dispersions with 1 and 2% w/w SDS. X-ray diffraction revealed that a complete molecular dispersion, i.e. a solid solution, of griseofulvin in PEG/SDS was obtained when 2% w/w SDS was incorporated. A continuous increase in dissolution rate with increase in concentration was observed for dispersions containing the other surfactants but polysorbate 80, Brij 35 and DTAB were not as effective as SDS in increasing the dissolution rate. X-ray diffraction revealed a decrease in the amount of crystalline griscofulvin with increase in surfactant concentration except with polysorbate 80, for which no changes were observed. Differential scanning calorimetry studies supported the results obtained by X-ray diffraction. A relationship between the solubilizing efficiency of the surfactant in aqueous solutions and its ability to increase the solid solubility of a drug in PEG, and subsequently the dissolution rate, was observed. Measurements after 12 months of storage revealed that the dissolution rate was unchanged for the dispersions without surfactant or with polysorbate 80. However, at higher concentrations of Brij 35, DTAB and SDS, the dissolution rates were decreased upon storage.