ENHANCEMENT OF DISSOLUTION RATE OF HYDROCHLOROTHIAZIDE
Abstract
Objective: The aim of this study was to enhance the dissolution rate of hydrochlorothiazide (HCTZ).
Methods: Binary solid dispersions (SDs) of HCTZ with increasing weight ratios of poloxamer 407, polyethylene glycol 6000 (PEG 6000) or gelucire 50/13 were prepared by solvent evaporation technique. The solid dispersions were deposited on the surface of aerosil 200 to produce a dry product with large surface area. The SDs were characterized with respect to drug dissolution. The mechanism of dissolution enhancement was researched using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).
Results: The unprocessed drug showed erratic, slow dissolution which can be explained on the basis of its hydrophobic nature. Preparation of SDs with hydrophilic carriers resulted in a significant increase in the dissolution rate with most of the drug being liberated in the first 5 min. The dissolution pattern of the drug from the prepared SDs depends mainly on the type of polymer used, and the best dissolution pattern was observed in the SD prepared using 1:1 ratio of the drug to gelucire 50/13 in the presence of aerosil 200 as a carrier. FTIR studies revealed no interaction between the drug and polymers. DSC showed a change in the crystalline structure of the drug after SDs formation. This change can explain the recorded dissolution enhancement.
Conclusion: The study presented a system capable of increasing the dissolution rate of HCTZ using polymers which can increase the intestinal permeability as well.
Keywords: Hydrochlorothiazide, Poloxamer 407, PEG 6000, Gelucire 50/13, Solid dispersion, Dissolution
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References
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