Abstract
Polymorphism in active pharmaceutical ingredients can be regarded as critical for the potential that crystal form can have on the quality, efficacy, and safety of the final drug product. The current contribution aims to characterize thermodynamic interrelationship of a dimorphic co-crystal, FI and FII, involving carbamazepine (CBZ) and saccharin (SAC) molecules. Supramolecular synthesis of CBZ-SAC FI and FII has been performed using thermokinetic methods and systematically characterized by differential scanning calorimetry, powder X-ray diffraction, solubility, and slurry measurements. According to the heat of fusion rule by Burger and Ramberger, FI (ΔHfus = 121.1 J/g; melting point, 172.5°C) and FII (ΔHfus = 110.3 J/g; melting point, 164.7°C) are monotropically related. The solubility and van't Hoff plot results suggest FI stable and FII metastable forms. This study reveals that CBZ-SAC co-crystal phases, FI or FII, could be stable to heat-induced stresses; however, FII converts to FI during solution-mediated transformation.
Highlights
Co-crystals1-3 are crystalline entities that comprise more than 1 component in a defined stoichiometric ratio and are held together by noncovalent interactions
The calculated density of FI was found to be higher than FII, which is in line with the close packing observed in FI (70.2%) over FII (69%)
Polymorphism in molecular crystals involving one-component systems, such as active pharmaceutical ingredients (APIs), has been widely investigated, but limited reports are available on the multicomponent systems such as cocrystals of APIs and their thermodynamic behavior
Summary
Co-crystals are crystalline entities that comprise more than 1 component in a defined stoichiometric ratio and are held together by noncovalent interactions. Co-crystals of active pharmaceutical ingredients (APIs) show great promise in improving pharmaceutically relevant properties, such as dissolution, bioavailability, compressibility, physical stability, and photostability.. Pharmaceutical companies are focusing on development aspects of co-crystals that include physicochemical characterization, scale-up, processing, and formulations of these novel materials.. Polymorphism in APIs is well known and regarded as critical for the potential that crystal form can have on the quality, efficacy, and safety of the final drug product.. Ritonovir, an antiviral drug found to exist in 2 polymorphic forms (forms I and II), showing significantly different bioavailabilities between these crystalline phases has forced Abbott to change its formulation.. Co-crystals of active pharmaceutical ingredients (APIs) show great promise in improving pharmaceutically relevant properties, such as dissolution, bioavailability, compressibility, physical stability, and photostability. pharmaceutical companies are focusing on development aspects of co-crystals that include physicochemical characterization, scale-up, processing, and formulations of these novel materials. Polymorphism in APIs is well known and regarded as critical for the potential that crystal form can have on the quality, efficacy, and safety of the final drug product. As an example, ritonovir, an antiviral drug found to exist in 2 polymorphic forms (forms I and II), showing significantly different bioavailabilities between these crystalline phases has forced Abbott to change its formulation. In the last 2 decades, there is an increasing interest in the pharma industry for a thorough evaluation of polymorphs of
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