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Natural Plus Synthetic Hydrotropic Solubilization using Response Surface Methodology to Optimize the Solid Dispersion of Hydrochlorothiazide

Author(s):

Arun Saharawat, Deepali* and Nidhi Nainwal   Pages 1 - 17 ( 17 )

Abstract:


Background: Solubility/dissolution is said to be the key factor that influences the oral bioavailability of drug and is also the rate limiting step in formulation development.

Objective: Hydrochlorothiazide (HCZ) is a BCS Class IV drug with low solubility and low permeability. The present work aimed to increase the solubility of hydrochlorothiazide using blends of natural and synthetic hydrotropes.

Methods: Two hydrotropes one from natural (piperazine) and other from synthetic origin (sodium benzoate) were selected for the formulation of solid dispersion (SD) of HCZ. Preliminary trial batches were prepared by considering the safe dose of both the selected hydrotropes i.e. sodium benzoate (SB) and piperazine (PP). A 32 full factorial design was opted for preparing the optimized solid dispersion of hydrochlorothiazide.

Results: The quadratic models were found to be best fitted for the studied responses, which were percent solubility and invitro drug release. The results showed increased solubility and in-vitro drug release of HCZ solid dispersions as a function of increasing levels of both hydrotropes.

Conclusion: In this work, it was concluded that the use of natural hydrotropes along with synthetic hydrotropes gave an effective and safe approach for the solubility enhancement of the HCZ.

Keywords:

Hydrochlorothiazide, piperazine, sodium benzoate, 32 full factorial design, solid dispersion

Affiliation:

School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, Uttarakhand 248001, School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, Uttarakhand 248001, School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, Uttarakhand 248001



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