Investigation of the formation of drug-drug cocrystals and coamorphous systems of the antidiabetic drug gliclazide

Publication date: Available online 23 February 2019Source: International Journal of PharmaceuticsAuthor(s): Marwah Aljohani, Pól MacFhionnghaile, Patrick McArdle, Andrea ErxlebenAbstractThe antidiabetic drug gliclazide (GLZ) has a slow absorption rate and a low bioavailability due to its poor solubility. GLZ is often prescribed along with an antihypertensive, as many diabetic patients have coexistent hypertension. Cocrystallization and coamorphization are attractive strategies to enhance dissolution rates and to reduce the number of medications a patient has to take. In this work the formation of cocrystals and coamorphous systems of GLZ with various antihypertensive drugs was studied, namely chlorothiazide (CTZ), hydrochlorothiazide (HTZ), indapamide (IND), triamterene (TRI) and nifedipine (NIF) as well as benzamidine (BZA) as a model for the amidine pharmacophore. TRI, IND and HTZ were found to form coamorphous systems with GLZ that are stable for at least six months at 22 ± 2 °C and 56 % relative humidity. Coamorphous GLZ-TRI is also stable in dissolution medium. Coamorphization of GLZ-TRI with 15 % sodium taurocholate gave a viable coamorphous formulation with an enhanced dissolution rate. Comilling of GLZ with BZA and cocrystallization from solution gave the amorphous and crystalline salt, respectively and the X-ray structure is reported. During attempts to obtain X-ray suitable cocrystals crystals of Na+GLZ- and IND 0.5H2O were obtained. Redeterminatio...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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