Juhee Lim1,Jonghwi Lee1
Chung-Ang University1
Particle engineering of pharmaceutical and food ingredients by crystallization is important and widely used to meet the complex requirements. By adding a small amount of polymer during crystallization, various properties such as bioavailability, crystal stability, and drug release control can be controlled, and many advantages such as high efficiency and cost reduction can be obtained. This polymer-directed crystallization can trigger crystal formation through a route of non-classical crystallization, which is mediated by the physical adsorption of long-chain molecules. We hypothesized that by polymer-induced crystallization, one polymer could connect crystals of two different drug molecules. Composite drug crystals can obtain advantages such as improved processability and stability, reduced number of drug tablets, and reduced price by making two drugs into one tablet. The two drugs used in this study are the antihypertensive drugs Valsartan (VAL) and Amlodipine besylate (AMB). The polymer dissolved in the solution is adsorbed on the surfaces of the nuclei, and the crystals form an assembly of crystals. OM and SEM showed two different types of crystals. Additionally, crystallinity changes were observed through birefringence observation. The melting point measurements by differential scanning calorimetry showed that the melting point of the two drugs were significantly changed in the composite crystal, indicating significant change in the interaction between the drugs and polymer. Powder X-ray diffraction showed that the crystal form changed according to the composition ratio of the drug. The proton nuclear magnetic resonance confirmed the composition ratio of the obtained crystals, and as a result, it was indicated that the precipitated ratio was like the added ratio. This novel complex crystal manufacturing method may provide new opportunities for convenient production of complex formulations and improved processability and stability.