USE OF SCANNING ELECTRON-MICROSCOPY TO STUDY THE EFFECT OF SURFACTANT ON THE IN-VITRO RELEASE OF VALPROIC ACID FROM COATED PARTICLES

In vitro release of valproic acid (VA) from Depakote(R) coated particles was studied in simulated gastric fluid for 1 hour followed by simulated intestinal fluid for 7 hours. The release studies were carried out using a Bio-Dis II(R) Dissolution Apparatus. VA concentration was determined by gas-liquid chromatography (GLC), using a 6 ft x 2 mm glass column packed with 10% w/w SP-1000 (Supelco). In vitro release studies indicated that 17.18 +/- 0.66% w/w (mean +/- standard deviation, SD; n = 6) of the incorporated drug was released in simulated gastric fluid in 1 hour. The effect of a nonionic surfactant (Tween 20) and an anionic surfactant (bile salt) on the release characteristics of drug from these coated particles in simulated intestinal fluid was also investigated. In the presence of surfactant, even at a very low concentration, drug release from these particles was complete within 3 hours. In the absence of surfactant, only 70.2 +/- 1.03% w/w (mean +/- SD; n = 3) of the drug was released within the same time period. The increase in rate and extent of release was believed to be due to the surface tension lowering effect of the surfactant, which resulted in increase wetting and penetrability of the medium into the particles. Direct visual observation of the microstructure of the particles before and after in vitro release studies by scanning electron microscopy supported the above hypothesis.