Solubility Enhancement of Hydrochlorothiazide using a Novel Drug-Drug Solid Dispersion Technology

DOI:

https://doi.org/10.37285/ijpsn.2015.8.3.6

Authors

  • Rakshit N Sonpal
  • Pragna Shelat
  • Anita lalwani

Abstract

Fixed dose combination (FDC) is commonly used in pharmaceuticals to reduce pill burden and optimize the drug therapy. The recent advancements in combinatorial chemistry often lead to drugs with low aqueous solubility. Many FDC’s contain at least one drug with suboptimal physicochemical properties like BCS class II drugs for which its poor aqueous solubility may often be a limiting factor to its bioavailability. Considering the above fact, a novel drug – drug solid dispersion has been developed in present study, wherein a poorly soluble drug hydrochlorothiazide has been solid dispersed in a hydrophilic drug, Metoprolol tartrate with which it is available as a FDC. Hydrochlorothiazide was solid dispersed in Metoprolol tartrate in ratios as available in market and also in conventional carrier mannitol by melting method. Physical mixtures of the two drugs and hydrochlorothiazide and mannitol were also prepared in the same ratio. Physical mixture did not show any signs of incompatibility in the FTIR study. In vitro dissolution study showed that t90% was less for solid dispersion (SDMT4) as compared to pure drug and physical mixture of the two drugs and so was selected for further study. The SDMT4 batch was then subjected to DSC analysis and XRD study, where the results suggested amorphization of hydro-chlorothiazide. Tablets were prepared from the SDMT4 batch and the in vitro release profile was compared to marketed formulation of hydrochlorothiazide. Tablets were subjected to accelerated stability analysis for 6 months at 40 °C and 75 % RH and were found to remain stable. Pharmacokinetic analysis was carried out with pure drug and SDMT4 and relative bioavailability was estimated to be 1.21. Thus a novel concept where in one drug is solid dispersed in other was hypothesized and proved. The concept can be explored for many such FDC’s.

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Keywords:

Hydrochlorothiazide, Metoprolol, Mannitol, Drug-drug dispersion, solubility.

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Published

2015-08-30

How to Cite

1.
Sonpal RN, Shelat P, lalwani A. Solubility Enhancement of Hydrochlorothiazide using a Novel Drug-Drug Solid Dispersion Technology. Scopus Indexed [Internet]. 2015 Aug. 30 [cited 2024 Dec. 10];8(3):2924-36. Available from: https://www.ijpsnonline.com/index.php/ijpsn/article/view/784

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Section

Research Articles

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