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Published on: August 9, 2022
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Interrelation of the dissolution behavior and solid-state features of acetazolamide cocrystals
Jenniffer I Arenas-García1, Dea Herrera-Ruiz1, Hugo Morales-Rojas2
1Facultad de Farmacia, Universidad Autónoma del Estado de Morelos. Av. Universidad 1001, C.P. 62209 Cuernavaca, Mexico.
Summary
Acetazolamide (ACZ) cocrystals with various formers show enhanced dissolution rates, particularly those transforming in simulated physiological conditions. Solid-state stability inversely correlates with dissolution, highlighting its impact on performance.
Area of Science:
- Pharmaceutical Science
- Solid-State Chemistry
Background:
- Acetazolamide (ACZ) is a crucial pharmaceutical ingredient.
- Cocrystal formation is a strategy to improve drug properties.
Purpose of the Study:
- Evaluate thermal behavior, phase stability, and dissolution rates of ACZ cocrystals.
- Investigate the impact of cocrystal formers on ACZ stability and dissolution.
Main Methods:
- Cocrystal synthesis with acetazolamide and six different cocrystal formers.
- Thermal analysis (DSC/TGA), powder X-ray diffraction (PXRD).
- Intrinsic dissolution rate (IDR) studies and phase stability tests in simulated physiological conditions (pH 2.0).
Main Results:
- Most cocrystals showed thermal decomposition of acetazolamide after crystal former elimination.
- Cocrystals with nicotinamide (NAM) exhibited melting.
- All cocrystals were stable under controlled humidity but ACZ-NAM-H2O and ACZ-PAM transformed in acidic media.
- Cocrystals demonstrated significantly enhanced intrinsic dissolution rates compared to pure ACZ, with the highest rates for those transforming in acidic media.
Conclusions:
- Cocrystal formation can enhance acetazolamide dissolution rates.
- Solid-state stability is a critical factor influencing dissolution performance, showing an inverse correlation with dissolution rates.
- Cocrystals that transform in simulated physiological conditions exhibit improved dissolution, suggesting potential for enhanced bioavailability.
Keywords:
2,3-Dihydroxybenzoic acid (PubChem CID:19)2-Aminobenzamide (PubChem CID:6942)2-Hydroxybenzamide (PubChem CID:5147)4-Hydroxybenzoic acid (PubChem CID:135)Acetazolamide (PubChem CID:1986)Cocrystal hydratesCocrystalsDissolution rateNicotinamide (PubChem CID:936)Picolinamide (PubChem CID:15070)Solution mediated phase transformationThermal analysis
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