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Description
Acetazolamide (ACZ) is a carbonic anhydrase inhibitor primarily indicated for glaucoma and used as an ancillary therapy for epilepsy, diuresis, and high-altitude sickness, and edema caused by congestive heart failure, as well as preventing drug-related side effects in the treatment of influenza.[1,2] ACZ, being a class IV member of biopharmaceutics classification system, possesses limiting solubility and permeability. In order to target the poor permeation profiles of such drugs, pharmaceutical cocrystals have emerged as novel tools in recent years.[3,4] Incorporation of a coformer inside the crystal lattice of a drug by means of weaker non-covalent interactions results in the development of cocrystal which exhibits modified crystal arrangement and molecular packing compared to the parent components. Since intrinsic properties of a molecule rely on its crystal structure, therefore rearranging the crystal packing of a drug is thought to manifest modulated permeability. In this regard, the ability of drug molecules to cross the biological membrane is a critical factor. Among the many cell-monolayer models currently available to mimic the human intestinal epithelium, the Caco-2 cell monolayer is most commonly employed because it is reliable and shows a strong correlation with the in-vivo absorption through the gastrointestinal epithelium. In the present study, the effect of cocrystallization of ACZ with p-aminobenzoic acid (PABA) on the CaCO-2 permeation profile of the parent drug has been shown methodologically.
REFERENCES
1. Arenas-Garcia, J.I., Herrera-Ruiz, D., Mondragón-Vásquez, K., Morales-Rojas, H. and Höpfl, H., 2010. Co-crystals of active pharmaceutical ingredients-acetazolamide. Crystal growth & design, 10(8), pp.3732-3742.
2. Arenas-Garcia, J.I., Herrera-Ruiz, D., Mondragon-Vasquez, K., Morales-Rojas, H. and Höpfl, H., 2012. Modification of the supramolecular hydrogen-bonding patterns of acetazolamide in the presence of different cocrystal formers: 3: 1, 2: 1, 1: 1, and 1: 2 cocrystals from screening with the structural isomers of hydroxybenzoic acids, aminobenzoic acids, hydroxybenzamides, aminobenzamides, nicotinic acids, nicotinamides, and 2, 3-dihydroxybenzoic acids. Crystal growth & design, 12(2), pp.811-824.
3. Zhang, Y.X., Wang, L.Y., Dai, J.K., Liu, F., Li, Y.T., Wu, Z.Y. and Yan, C.W., 2019. The comparative study of cocrystal/salt in simultaneously improving solubility and permeability of acetazolamide. Journal of Molecular Structure, 1184, pp.225-232.
4. Song, Y., Wang, L.Y., Liu, F., Li, Y.T., Wu, Z.Y. and Yan, C.W., 2019. Simultaneously enhancing the in vitro/in vivo performances of acetazolamide using proline as a zwitterionic coformer for cocrystallization. CrystEngComm, 21(19), pp.3064-3073.