Formulation and development of solid self micro-emulsifying drug delivery system (S-SMEDDS) containing chlorthalidone for improvement of dissolution
Dangre Pankaj V., Gilhotra Ritu M., Dhole Shashikant N.,
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( Dangre Pankaj V. )
Kamla Nehru College of Pharmacy Department of Pharmaceutics
( Gilhotra Ritu M. )
Suresh Gyan Vihar University Department of Pharmaceutics
( Dhole Shashikant N. )
Modern College of Pharmacy Department of Pharmaceutics
Abstract
The objective of the present study was to develop a self micro-emulsifying drug delivery system (SMEDDS) of chlorthalidone (CTD) to improve its solubility and dissolution. CTD is a diuretic agent belongs to Biopharmaceutics classification system (BCS)-IV category having poor solubility and permeability. Solubility study of CTD was carried out in various excipients. Based on solubility study, Capmul MCM as oil, Tween 80 as surfactant and PEG 400 as co-surfactant were selected as a component of liquid SMEDDS formulation. The pseudo-ternary phase diagram was constructed to identify the optimum composition of the formulation. The optimum formulation showed emulsification time 42 ¡¾ 3.3 s, cloud point 72 ¡¾ 2 ¡ÆC, globule size 174.2 ¡¾ 1.1 nm and zeta potential ?9.92 ¡¾ 1.2 mV. The optimized SMEDDS formulation was transferred on to the inert adsorbent i.e. Neusilin US2, to formed a solid self emulsifying drug delivery system (S-SMEDDS). Solid SMEDDS with 1:1 ratio (adsorbent: SMEDDS) showed excellent oil adsorption capacity, low bulk density and good flow properties. Furthermore, DSC, PXRD and SEM studies indicated the transformation of crystalline structure of CTD to amorphous and molecularly dissolved state. In vitro dissolution study indicates high dissolution rate of solid-SMEDDS over the pure drug and marketed formulation. Thus, SMEDDS formulation helps to improve the solubility and dissolution of CTD.
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Chlorthalidone; BCS-IV; Solid SMEDDS; Neusilin US2; Dissolution
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