Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug-Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
The mechanochemical synthesis of drug-drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug-drug eutect...
محفوظ في:
| المؤلفون الرئيسيون: | , , , , , , , , , |
|---|---|
| التنسيق: | كتاب |
| منشور في: |
MDPI AG,
2021-11-01T00:00:00Z.
|
| الموضوعات: | |
| الوصول للمادة أونلاين: | Connect to this object online. |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| الملخص: | The mechanochemical synthesis of drug-drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug-drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy analysis (SEM-EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χ<sub>MET·HCl</sub> = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χ<sub>MET·HCl</sub> = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔH<sub>fus</sub> and ΔS<sub>fus</sub>) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms. |
|---|---|
| وصف المادة: | 10.3390/pharmaceutics13111926 1999-4923 |