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Formulation and development of solid self micro-emulsifying drug delivery system (S-SMEDDS) containing chlorthalidone for improvement of dissolution

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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 ± 3.3 s, cloud point 72 ± 2 °C, globule size 174.2 ± 1.1 nm and zeta potential −9.92 ± 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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Acknowledgments

The authors sincerely thankful to the secretary of Kamla Nehru College of Pharmacy, Butibori, Nagpur, India for providing the instrumental facility for carrying out the research work. The authors are also thankful to Ipca Laboratories, Mumbai, India for providing the gift sample of chlorthalidone. This article does not contain any studies with human and animal subjects performed by any of the authors.

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Authors have no conflict of interest with the content of this article.

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Authors and Affiliations

  1. Department of Pharmaceutics, Kamla Nehru College of Pharmacy, Butibori, Nagpur, Maharashtra, 441108, India

    Pankaj V. Dangre

  2. Department of Pharmaceutics, Suresh Gyan Vihar University, Mahal, Jagtpura, Jaipur, Rajasthan, 302025, India

    Pankaj V. Dangre & Ritu M. Gilhotra

  3. Department of Pharmaceutics, Modern College of Pharmacy (For Ladies), Moshi, Pune, Maharashtra, 421105, India

    Shashikant N. Dhole

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  1. Pankaj V. Dangre
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  2. Ritu M. Gilhotra
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  3. Shashikant N. Dhole
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Correspondence to Pankaj V. Dangre.

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Dangre, P.V., Gilhotra, R.M. & Dhole, S.N. Formulation and development of solid self micro-emulsifying drug delivery system (S-SMEDDS) containing chlorthalidone for improvement of dissolution. Journal of Pharmaceutical Investigation 46, 633–644 (2016). https://doi.org/10.1007/s40005-016-0243-2

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  • DOI: https://doi.org/10.1007/s40005-016-0243-2

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