Thermal and rheological study of lipophilic ethosuximide suppositories

Abstract

We have performed thermal (differential scanning calorimetry) and rheological studies in the preformulation phase of ethosuximide suppositories to determine the influence of the active ingredient and adjuvants on the melting characteristics and rheological performance of the suppositories. Both types of studies were performed on the fatty bases witepsol H-19 and suppocire AP, each mixed with 5% w/w polysorbate 80, 0.1% w/w docusate sodium and 3% w/w tetranyl AT-1/DP and on the suppository formulations obtained by the addition of 150 mg of ethosuximide to these excipients. Pure lipophilic excipients have two peaks in the DSC curve. The first one occurs at lower temperatures (27.35°C for the suppocire AP and 34.3°C for the witepsol H19) and the second peak at higher temperatures (36.27 and 35.95°C for the suppocire AP and witepsol H19, respectively). Polysorbate 80, docusate sodium and tetranyl AT-1/DP cause the first melting peak to disappear and the second peak to occur at a lower temperature. The thermograms of the formulas show two melting peaks and the endothermic peak does not appear due to the melting of ethosuximide (47.8°C). We attribute this behavior to the solubility of the drug in the melted excipient, thus originating a decrease of the melting temperature of the second peak in the DSC scan. The excipients and formulations behave as Newtonian fluids and the influence of ethosuximide and adjuvants can be noted in an increase in the viscosity of the suppository mass. © 2003 Elsevier Science B.V. All rights reserved.