(1) Drug solubility and molecular structure: The solubility of a drug in a solvent is the result of the interaction between drug molecules and solvent molecules. If the intermolecular force of the drug is greater than the intermolecular force between the drug molecule and the solvent molecule, the solubility of the drug is small;On the contrary, the solubility is large, that is, "similar dissolution". Hydrogen bonding has a great effect on drug solubility. In polar solvents, solubility increases if hydrogen bonds can be formed between the drug molecules and the solvent molecules. If the drug molecule forms intramolecular hydrogen bonds, the solubility in polar solvents decreases and increases in non-polar solvents. Soluble salts made from organic weak acids and weak alkaline drugs can increase their solubility. The introduction of hydrophilic groups into poorly soluble drug molecules increases solubility in water. If vitamin K3 is insoluble in water, the introduction of -SO3 DNA into the molecule becomes vitamin K3 sodium bisulfite, which can be made into injections.
2) Solvation and hydration: The solvation of the drug will affect the solubility of the drug in the solvent.
3) The influence of polymorphism: different crystal forms lead to different lattice energy, and the melting point, dissolution speed, solubility and so on of drugs are also different. For example, vitamin B2 has three crystal forms, and the solubility in water is as follows: type, 60mg L;type, 80 mg l;type, 120 mg l. Amorphous is a drug with no crystalline structure, no lattice binding, and large free energy, so the solubility and dissolution rate are larger than those of crystalline type. In most cases, solubility and dissolution rate are in the order of hydrates, anhydrous, and organics. For example, the solubility of sulfadiazine succinate hydrate is 10mg 100ml, the solubility of anhydrous is 39mg 100ml, and the solubility of pentanol solvate is 80mg 100ml. (4) Effect of particle size: For insoluble drugs, the particle size has no effect on the solubility when the particle radius is greater than 2000nm, but the particle size is 01 The solubility increases with the decrease of particle size at 100 nm.