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
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.