Abstract
Here, we report the synthesis and experimental characterization of three drug-drug eutectic mixtures of drug aminoglutethimide (AMG) with caffeine (CAF), nicotinamide (NIC) and ethenzamide (ZMD). The eutectic mixtures i.e., AMG-CAF (1:0.4, molar ratio), AMG-NIC (1:1.9, molar ratio) and AMG-ZMD (1:1.4, molar ratio) demonstrate significant melting point depressions ranging from 99.2 to 127.2 °C compared to the melting point of the drug AMG (151 °C) and also show moderately higher aqueous solubilities than that of the AMG. The results presented include the determination of the binary melt phase diagrams and accompanying analytical characterization via X-ray powder diffraction, FT-IR spectroscopy and scanning electron microscopy.
Highlights
The multicomponent solid form of the drug is rapidly emerging as an effective way to improve the drug physiochemical properties such as solubility, dissolution rate, bioavailability and other crucial pharmaceutical properties like stability, hygroscopicity, chemical stability, flowability, etc. [1,2,3,4,5,6,7]
In the case of multicomponent systems with the coformers CAF, NIC and ZMD, the adhesive interactions are relatively weaker as they are non-isomorphous molecules with a considerable mismatch in size and shape
Solvent-assisted mechanochemical grinding of the drug aminoglutethimide with pharmaceutical coformers enabled the production of binary eutectic mixtures
Summary
The multicomponent solid form of the drug is rapidly emerging as an effective way to improve the drug physiochemical properties such as solubility, dissolution rate, bioavailability and other crucial pharmaceutical properties like stability, hygroscopicity, chemical stability, flowability, etc. [1,2,3,4,5,6,7]. Eutectic mixtures are multicomponent compounds made up of two or more crystalline solids that show immiscibility in the solid-state and do not combine to generate a new chemical compound but, at a certain ratio, the eutectic composition will exhibit a melting or solidification point significantly lower than its constituents [1,4,8]. Eutectic mixtures generally exhibit high thermodynamic parameters, for example, free energy, enthalpy and entropy etc., which alter the solubility and dissolution behavior [1]. The eutectic mixture of curcumin and nicotinamide in a 1:2 ratio exhibits a 10-fold faster intrinsic dissolution rate [14]. Another aspect is that it is critical to identifying the production of eutectics during the formulation stage to minimize manufacturing difficulties [15,16]. During pharmaceutical research, understanding eutectic mixtures can aid in the discovery of compounds with equivalent melting points
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