Intrinsic solubility means that the drug does not contain any impurities, does not dissociate or associate in the solvent, and does not interact with the concentration of the saturated solution formed. It is one of the important physical parameters of the drug. Especially for new compounds. From the perspective of formulation, the characteristic solubility of a new drug is the first parameter that should be measured, because after understanding this parameter, appropriate consideration can be given to the selection of formulation dosage form, as well as prescription, process, drug crystal form, particle size, etc. In many cases, absorption problems may occur if the characteristic solubility of oral drugs is less than 1 mg/ml. Obviously, this index has a certain correlation with the dissolution rate and has equivalent significance. Medicilon Biomedicine has extensive experience in compound solubility testing and compound solubility determination methods.
service items
◇Test method of compound solubility: HPLC-UV
◇Development of detection method
◇Confirmation of detection method (to do quantitation limit, linearity and precision)
◇Solubility test
HPLC determination of compound solubility experiment
Advantages: This experiment is particularly suitable for the determination of insoluble compounds in pure water!
Charges
◇With or without compound
◇Different according to the difficulty of the method and the type of solvent
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Pharmacopoeia on the determination of solubility
The pharmacopoeia of each country stipulate the method for the determination of solubility. The 2000 edition of the Chinese Pharmacopoeia stipulates detailed measurement methods. The time for dissolution to reach equilibrium also differs depending on the binding capacity of the solute molecules and the solvent molecules, ranging from a few seconds to tens of hours. It is not easy to completely exclude the effects of drug dissociation and solvents in the actual measurement, especially for acid and alkaline drugs.
1. Characteristic solubility and determination method of drugs
The intrinsic solubility of a drug means that the drug does not contain any impurities, does not dissociate or associate in the solvent, and does not interact with the concentration of the saturated solution formed. It is one of the important physical parameters of the drug. Especially for new compounds. From the perspective of formulation, the characteristic solubility of a new drug is the first parameter that should be measured, because after understanding this parameter, appropriate consideration can be given to the selection of formulation dosage form, as well as prescription, process, drug crystal form, particle size, etc. In many cases, absorption problems may occur if the characteristic solubility of oral drugs is less than 1 mg/ml. Obviously, this index has a certain correlation with the dissolution rate and has equivalent significance.
Of the commonly used drugs, about 75% are weakly acidic drugs and about 20% are weakly basic drugs. To accurately determine the characteristic solubility, weakly acidic drugs and weakly basic drugs should be measured in acidic and alkaline solutions, even so, it is not easy to completely exclude the effects of drug dissociation and solvents in the measurement. Therefore, in general, the solubility measured is usually equilibrium solubility (equilibrium solubility) or apparent solubility (apparent solubility).
The determination of the characteristic solubility is based on the principle diagram of compatibility. In the case of measuring several supersaturated solutions of different degrees, the prepared solution is continuously shaken at a constant temperature to achieve dissolution equilibrium. After centrifugation or filtration, the supernatant is taken out and diluted appropriately to determine the concentration of the drug in the saturated solution. The measured drug solution concentration is taken as the ordinate, the drug mass-solvent volume ratio is plotted as the abscissa, and the straight line extrapolation to the ratio is zero to obtain the characteristic solubility of the drug. The positive deviation in Figure 9-1 indicates that the drug dissociates in this solution, or the impurity components or solvents have a compound and solubilizing effect on the drug (curve A) Medicine|Education Net Collecting and finishing; line B indicates that the drug has high purity and no solution Separation, and association, no interaction; negative deviation indicates the occurrence of the same ion effect (curve C) that inhibits dissolution. The solubility shown by the intersection of the two curves extrapolated with the vertical axis is the characteristic solubility S0.
2. The equilibrium solubility of the drug and its determination method
The solubility value of the drug is mostly the equilibrium solubility. The specific method of measurement is: take several parts of the drug, prepare a series of solutions from unsaturated solution to saturated solution, oscillate to equilibrium at constant temperature, filter through the filter membrane, take the filtrate for analysis and determination The actual concentration S of the drug in the solution is plotted against the concentration c of the prepared solution, as shown in Figure 9-2. The turning point A of the curve in the figure is the equilibrium solubility of the drug.
Whether it is to determine the equilibrium solubility or to determine the characteristic solubility, generally need to be carried out under two conditions of low temperature (4 ~ 5 ℃) and body temperature (37 ℃), in order to consider the storage and use of drugs and their preparations. If you need to further understand the effect of drug stability on solubility, the test should also use both acidic and basic solvent systems.
When measuring the solubility, pay attention to the constant temperature stirring and the time to reach equilibrium. The dissolution equilibrium time of different drugs in solvents is different. When measuring samples, keep the temperature consistent with the test temperature and filter out undissolved drugs, which is the main factor affecting the measurement.
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