A Comparison Between Nonionic Micelles and Microemulsions As A Means of Incorporating the Poorly Water Soluble Drug Diazepam

Abstract

The ease of preparation, thermodynamic stability, optical transparency and ability to sterilise by filtration renders microemulsion systems an attractive prospect for use in d r q delivery. In this investigation we attempt to determine whether these systems offer advantages over micellar preparations in the formulation of poorly water soluble drugs.We compare the incorporation of a model poorly water soluble drug, diazepam (log P =2.6), in both micellar solutions of polyoxyethylene-10-oleyl ether (Brij 96), and in O/W microemulsion systems consisting of 2%w/w soyabean oil, with varying concentrations of Brij 96. The microemulsion systems were clear (disperse phase droplets less than 30nm), non-birefringent and stable before and after the addition of diazepam. Solubilities were determined by stirring a known excess of diazepam into each sample and allowing equilibrium to be achieved in a shaking water bath at 25OC for 8 days. The samples were then passed through a 0.22um filter and the concentration of the resulting clear preparations determined by dilution with OS%w/v sulphuric acid in methanol and subsequent absorbance readings taken at 284nm. 1- .A 2% soyabean oil microemulsion 0 micellar solution The similarity in the amount incorporated in both types of systems may be explained b Y consideration of the site of solubilisation. This has been studied using dimethoxytetraethylene glycol (DMTG) / water mixtures, in which pure DMTG is chosea to represent the local environment of dehydrated polyoxyethylene (Patel et a1 (1981)).Results show an exponential increase in diazepam solubility with increasing DMTG. Thisindicates that the major site of diazepam incorporation in both microemulsion and micellar systems is the region of concentrated, dehydrated polyoxyethylene chains that occurs close to the oil or hydrocarbon core.It therefore appears that unless a drug has significant solubility in the dispersed oil phase of a microemulsion these systems offer little advantage over micellar ones for increadG the amount of drug which can be incorporated.Patel, M.S. et a1 (1981) J. Pharm. Pharmacol. 33(suppl.): 64P

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