RESUMEN
AIM: Spherical crystallization is a process of formation of agglomerates of crystals held together by binder liquid. This research focused on understanding the effect of type of solvents used as binder liquid on the agglomeration of crystals. METHOD: Carbamazepine and ethanol/water were used respectively as a model drug and crystallization system. Eight solvents as binder liquid including chloroform, dichloromethane, isopropyl acetate, ethyl acetate, n-hexane, dimethyl aniline, benzene and toluene were examined to better understand the relationship between the physical properties of the binder liquid and its ability to bring about the formation of the agglomerates. Moreover, the agglomerates obtained from effective solvents as binder liquid were evaluated in term of size, apparent particle density and compressive strength. RESULTS: In this study the clear trend was observed experimentally in the agglomerate formation as a function of physical properties of the binder liquid such as miscibility with crystallization system. Furthermore, the properties of obtained agglomerates such as size, apparent particle density and compressive strength were directly related to physical properties of effective binder liquids. CONCLUSION: RESULTS of this study offer a useful starting point for a conceptual framework to guide the selection of solvent systems for spherical crystallization.
Asunto(s)
Carbamazepina/química , Cristalización/métodos , Excipientes/química , Solventes/química , Química Farmacéutica , Propiedades de SuperficieRESUMEN
In high shear wet granulation (HSWG), the interaction mechanism between binder and powder with different sugar content is still unclear. Herein, the law and mechanism of the interaction between binder and powder were studied on the molecular level by combining experiment analysis through the Kriging model and molecular dynamics (MD) simulation. For the sticky powder with high sugar content, the ethanol in the binder played a pivotal role in dispersing water into powders, and the amount of water determined the growth of granules. In the saturating stage, the reduction of sugar content facilitates the penetration of ethanol molecules. The concentration of ethanol determines whether the mixture is blended uniformly in the merging stage. The simulation results are consistent with the actual situation and explain the competition mechanism of interaction with binder and powder. Therefore, this research offers an efficient strategy for the in-depth understanding of the HSWG process where the powder is sticky, as well as providing guidelines for the practical application of preparation for Traditional Chinese Medicine (TCM) granules.