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Development and Optimization of Floating Capsule for Solid Self Microemulsified Drug Delivery of Hydrochlorothiazide

[ Vol. 13 , Issue. 1 ]

Author(s):

Swati Jagdale* and Pratik Phargade   Pages 83 - 97 ( 15 )

Abstract:


Background: Hydrochlorothiazide (HCTZ) is a thiazide diuretic and also possesses an anti-hypertensive effect. It is BCS class IV drug with very poor aqueous solubility and permeability.

Objective: The objective of the present work was to enhance the solubility and permeability of hydrochlorothiazide via self microemulsifying drug delivery system (SMEDDS) and to optimize gastro-retentive floating delivery for Solid-SMEDD.

Method: T Solubility of drug was determined in the oil, surfactant and co-surfactant. Pseudo ternary phase diagram was constructed to identify efficient self emulsifying region. SMEDDS was transformed into a free flowing powder. Non-effervescent floating capsules containing Solid SMEDDS of HCTZ was prepared. Factorial design was used to optimize gastro-retentive delivery of HCTZ using polymer HPMC K4M and HEC HX 250 as independent variables.

Results: SMEDDS consists of HCTZ, isopropyl myristate, tween 80 and PEG 400 as drug, oil, surfactant and co-surfactant. 1:1 ratio of the surfactant to co-surfactant gave larger transparent region for microemulsion. Ex-vivo drug release from SMEDDS was higher than plain drug at the end of 4 hrs. Magnesium hydroxide was used to convert SMEDDS to S-SMEDDS. ANOVA indicated that the drug release and swelling index were the most significant factors affecting gastro retentive drug delivery. Optimized batch F5 followed Zero order release model kinetics.

Conclusion: The study concluded enhanced solubility of drug by SMEDD. Floating capsules gave controlled drug release in the stomach for longer period of time which reduced the dosing frequency and improved the patient compliance.

Keywords:

Hydrochlorothiazide, SMEDDS, floating, capsule, solubility, S-SMEDDS.

Affiliation:

Department of Pharmaceutics, MAEER’s Maharashtra Institute of Pharmacy, MIT Campus, S. No. 124, Kothrud, Pune 411038, Department of Pharmaceutics, MAEER’s Maharashtra Institute of Pharmacy, MIT Campus, S. No. 124, Kothrud, Pune 411038

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