Zolmitriptan

Abstract

Liquisolid systems is an innovative technique for enhancing solubility, dissolution and bioavailability of poorly water soluble drugs. It involves changing of the drug in the liquid state into compressible and freely flowable dry powder throughout its absorption into appropriate porous carrier (e.g.microcrystalline cellulose), after that the powder coated with material has a highly adsorption capacity (known as colloidal silica).

Orally disintegrating tablets represent a novel dosage form that overcomes the difficultiess of swallowing and provides a fast onset of action.

Zolmitriptan is a slightly soluble drug used for treatment of acute headache of migraine; it's known to suffer from first pass effect with bioavailability of 40 %.

Also, the present work aimed to improve patient compliance suffering from migraine attack. Liquisolid systems of Zolmitriptan were prepared utilizing a mathematical model for the calculation of the required amounts of excipients necessary for the production of an acceptable compressible and flowable powder blend.

Preliminary screening was applied to optimize Zolmitriptan liquisolid systems that have acceptable flow properties and enhanced drug dissolution rate by utilizing different carrier to coating material ratios (R values) ranging from 10:1-35:1. (R value) and drug concentration in liquid vehicle had an effect on the flow properties and the dissolution rate of the prepared formulas. Liquisolid system formula with (R value) of 35 and drug concentration in liquid vehicle of 10 % showed better flow properties and enhanced drug release. This formula was further optimized into orodispersible tablets. Zolmitriptan ODTs were prepared by direct compression method using: 1. different types of superdisintegrants (sodium starch glycolate, croscarmellose sodium, and crospovidone) each one with three different concentrations (2.5, 5 and 7.5 % w/w), 2. different coating materials (Aerosil 200 and cab-O-sil), 3. different carrier materials

The drug-excipient compatibilities study showed no interaction of the drug with excipients.

10. The selected formula (F18), which contains 5% (w/w) crospovidone, which was prepared by direct compression method showed the shortest in vitro and in vivo disintegration time compared to other formulas.

11. In-vitro dissolution test of the optimized liquisolid orodispersible formula (F18) was significantly higher than DCT and marketed tablet .

12. The in vivo pharmacokinetic study suggests that the optimized formula F18 developed in this work may be useful for the treatment of acute migraine attack due to the enhanced dissolution rate and by passing hepatic first pass metabolism through the partial absorption from buccal mucosa.

13. Based on these results, it could be concluded that a promising quickly absorbed liquisolid orodispersible tablets of Zolmitriptan were successfully designed for treatment of acute migraine attack. Nevertheless, due to small number of the volunteers recruited in this study, the results can only be considered as a preliminary, and the effectiveness of the optimized (F18) should be clinically studied with a larger number of volunteers to confirm its clinical