Physicochemical Property Study

The chemical structure of a drug determines its physicochemical properties. The main factors affecting the physical and chemical properties of drugs are temperature, pH, type and content of solvents, and complex physiological environment.

Research on physicochemical properties of drugs in the early stage of drug development is helpful for high-throughput screening of hit compounds, guiding the optimization of lead compounds to obtain compounds with better activity and pharmacokinetic properties, and reducing the failure rate of new drug development. Early acquisition of physicochemical property parameters, on the one hand, is conducive to the optimization of biological determination methods, to ensure the accuracy of biological test data. On the other hand, it is beneficial to predict the problems encountered in vivo and in vitro processes, provide the basis for the analysis and interpretation of abnormal data in vivo and in vitro, and can guide the design of drug dosage forms and the selection of drug administration routes in the drug development stage. Therefore, the physicochemical properties of drugs are very important for biological research.

The behavioral characteristics of drugs in vivo are closely related to the chemical structure and physical properties of drugs. The physicochemical properties of drugs are important factors affecting gastrointestinal absorption, such as the degree of dissociation, lipophilicity, dissolution rate, and gastrointestinal stability have different effects on gastrointestinal absorption. For insoluble drugs, the dissolution process is the limited factor of absorption. Drug distribution is a process of transmembrane transport. Most drugs pass through cell membranes through micropores or lipid bilayers in a passive diffusion way. This transport mode is closely related to the physicochemical properties of drugs, such as molecular size, chemical structure, and configuration, pKa, lipophilicity, and polarity (PSA). The physicochemical properties of drugs are also the decisive factors of drug metabolism, which determine the plasma protein binding rate, liver tissue affinity, metabolic pathway, and enzyme catalytic mechanism of drugs. At the same time, the physicochemical properties of drugs are also important factors affecting the excretion and elimination of drugs, such as the size of molecular weight and polarity directly affect the excretion pathway of drugs, fat solubility, and dissociation affect the reabsorption rate of drugs in the renal tubules. Therefore, the various physical and chemical properties of drugs are closely related and jointly affect the pharmacokinetic behavior of drugs.