ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF TELMISARTAN BY TELMISARTAN-OXALIC ACID CO-CRYSTAL FORMATION
Keywords:
Telmisartan, Oxalic acid, Co-crystal, Solubility, DissolutionAbstract
Objective: Telmisartan (TMS), an angiotensin II receptor antagonist used for the prevention and treatment of hypertension has a very low solubility in water, so its dissolution rate is low. The aim of this study is to improve the water solubility and dissolution rate of TMS by telmisartan-oxalic acid (TMS-OXA) co-crystal formation.
Methods: Co-crystal was prepared by solvent-drop grinding and solvent evaporation methods with methanol as solvent. Initial characterization was performed by powder X-ray diffraction (PXRD). Co-crystal formation of TMS-OXA was also characterized by differential thermal analysis (DTA), Fourier transform infrared (FTIR) spectroscopy, polarized microscopy, and scanning electron microscope (SEM) photomicrograph. Solubility test was performed in water media at 25°C, whilst dissolution rate test was performed using the paddle method in 900 mL of pH 7.5 phosphate buffer solution at 37±0.5°C for 60 min.
Results: The PXRD patterns of TMS-OXA after both preparation methods were different from its starting components. There was no difference in the powder X-ray diffraction pattern between two preparation methods. The polarized photomicroscope and SEM photomicrograph showed the habit TMS-OXA co-crystal was a rhomboid shape. The solubility test showed the TMS-OXA co-crystal has 11.7 fold higher than pure TMS. The dissolution rate test showed that TMS-OXA co-crystal has percentage of TMS dissolved after 60 min higher than pure TMS.
Conclusion: The co-crystal TMS-OXA formation can increase the solubility and dissolution rate of TMS.
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References
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