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Formulation and evaluation of solid self-microemulsifying drug delivery system of chlorthalidone by spray drying technology
Authors:Jayshri Kailas Madagul  Durgesh Rameshlal Parakh  Rachana S. Kumar  Rakesh Ramesh Abhang
Affiliation:Department of Pharmaceutics, MET’s Institute of Pharmacy, Bhujbal Knowledge City, Nashik, Maharashtra, India
Abstract:The main objective of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) by spray drying liquid SMEDDS with an inert solid carrier Aerosil 200 to improve the dissolution rate and permeability of chlorthalidone (CTD). The liquid SMEDDS was composed of CTD, oleic acid, tween 20, and PEG 200. Preliminary screening was performed to select proper component combination. Solubility of CTD was determined in various vehicles. Ternary phase diagram for four series was constructed to delineate the boundaries of the nanoemulsion domain. Optimized S-SMEDDS (S3) was evaluated for dispersibility test (13.30?±?0.95), percentage transmittance (99.50?±?0.002), turbidity (260.43?±?1.02), percent drug content (97.86?±?0.56), droplet size (159.4), polydispersity index (PDI, 0.30), and zeta potential (?12.4). Solid-state characterization was done by scanning electron microscopy (SEM), differential scanning calorimetry, X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR). The XRD analysis confirmed that there was no crystalline CTD in the S-SMEDDS. SEM study revealed adsorption of liquid SMEDDS on Aerosil 200. In vitro drug release study was performed using water and 0.1N HCl as dissolution medium and compared with plain drug and marketed tablet Thaiklor TM 12.5, and marked increase in rate and extent of dissolution of S-SMEDDS was observed. Ex vivo intestinal permeability study revealed that diffusion of drug was significantly higher from S-SMEDDS than that of suspension of plain drug. The solid SMEDDS formulation was stable. In conclusion, the S-SMEDDS might be an encouraging strategy to improve the oral absorption of CTD.
Keywords:Chlorthalidone  dissolution  phase diagram  SEM  spray drying
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