SOLID DISPERSION OF CANDESARTAN CILEXETIL WITH HPMC: A COMPARATIVE STUDY OF FREEZE-DRYING AND SPRAY-DRYING TECHNIQUES

DENI NOVIZA; AZWITA

doi:10.22159/ijap.2025.v17s1.04

Authors

DENI NOVIZA Faculty of Pharmacy, Universitas Andalas, Sumatera Barat, 25175, Indonesia https://orcid.org/0009-0002-3500-2551
AZWITA Faculty of Pharmacy, Universitas Andalas, Sumatera Barat, 25175, Indonesia

DOI:

https://doi.org/10.22159/ijap.2025.v17s1.04

Keywords:

Candesartan cilexetil, Solid dispersion, Freeze drying, Spray-drying, Solubility

Abstract

Objective: The angiotensin II receptor antagonist candesartan cilexetil (CC) exhibits low bioavailability in humans, principally as a result of its limited aqueous solubility at low pH and the presence of a carboxyl moiety. To enhance the solubility of CC, this study aimed to develop solid dispersion (SD) systems incorporating hydroxypropyl methylcellulose (HPMC) as the polymer.

Methods: SD was fabricated through freeze-drying and spray-drying methods. utilizing HPMC as a hydrophilic polymer, eschewing the use of any organic solvents. Intact material and physical mixture were prepared as a comparison. Physicochemical properties of the intact material, physical mixture and SD were characterized employing the differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM). Solubility test was performed using shake flask method.

Results: The XRD analysis revealed a reduction in peak intensity for the SD. Additionally, thermal analysis indicated that the SD exhibited lower melting points than both the intact CC and the physical mixture. Moreover, the morphology of the SD displayed distinct shapes compared to the intact materials and the physical mixture. Additionally, Fourier-transform infrared (FT-IR) spectroscopy analysis revealed no shifts in the characteristic wavenumbers of the functional groups, indicating the absence of new functional group formation. Significantly, the solubility of the SD was markedly improved, as evidenced by the solubility test results: 3.37±1.12 μg/ml for intact CC, 31.39±1.45 μg/ml for the physical mixture, 35.43±1.87 μg/ml for the spray-dried SD, and 53.40±1.05 μg/ml for the freeze-dried SD.

Conclusion: The SD of candesartan cilexetil and hydroxypropyl methylcellulose successfully altered the physicochemical properties of the drug, resulting in a significant enhancement of its solubility.

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