Thermal analysis technology is a technology to measure the relationship between physical properties and temperature under the condition of controlled temperature. Through the study of these changes, the structure of materials could be identified . There are several advantages such as the less required amount of test articles, ease-of-use, and the flexibility of test conditions. Meanwhile, there are no special requirements for the shape of samples. The most important thing is that a variety of chemical and physical information could be obtained in one test . So the application scope of this technology is particularly wide. In the field of drug research, thermal analysis technology has gradually become the focus of drug quality research and new drug delivery system at home and abroad .
1. Application of in drug purity determination
Melting point is one of the important indexes to measure the quality of drugs. Measuring the melting point by thermal analysis technology can effectively control the heating rate and then obtain ideal accuracy. The theoretical basis for the determination of drug purity by thermal analysis technology is Van 't Hoff equation, that is, the decrease of drug melting point is directly proportional to the mass fraction of impurities. The lower the melting point, the longer the melting range, and the lower the purity.
2. Application of in the humidity inspection of drugs and the analysis of crystal water
The amount of water in drugs has an important impact on the stability of its effective components, excipients and finished products. Thermal analysis can easily distinguish whether the water contained in the sample is adsorbed on the particle surface or crystallized water combined in the compound, and quantitatively detect the molecular ratio of water or other volatile components. Compared with the loss on drying method, the thermal analysis method has a faster determination speed, and requires less sample dosage. So it is especially suitable for the determination of the humidity of more valuable drugs or drugs that are easy to oxidize in the air.
3. Application in quantitative analysis of drug components
Quantitative analysis of drug components includes identification of drug components, loss after drying, determination of ash and drug content, microbiological test, etc. Thermal analysis technology can determine the above contents by comparing the thermal spectrum curver between the pharmaceutical formula with the actual calibration compounds.
4. Application in the identification of authenticity of natural drugs
There is little difference in appearance and chemical properties between genuine and counterfeit natural drugs. Relying on appearance for identification has great subjective factors, and it is easy to confuse several drugs with similar appearance. Conventional chemical methods lack effective identification basis. Thermal analysis method is to identify the authenticity by using the different thermal analysis curves between genuine products and counterfeit products.
5. Application in the study of drug polymorph transformation
Drug polymorph phenomenon refers that the same drug has multiple crystal forms. The stability, solubility, dissolution and bioavailability of drugs are different with different crystal forms. Therefore, determining the crystal form of drugs plays an important role in the development of drug preparations and the exertion of drug efficacy. Different crystal forms have different melting point and melting enthalpy. Thermal analysis can not only measure the melting point and melting enthalpy, but also measure the phase transformation enthalpy during crystal form transformation. Therefore, thermal analysis has become a useful tool to study drug polymorph phenomenon and polymorph transformation .
6. Application in the analysis of various components in pharmaceutical preparations
The thermodynamic parameters that can be measured by thermal analysis include the changes of enthalpy and mass. The change of enthalpy or mass is directly proportional to the amount of substances in the sample, so the main components in the drugs can be detected qualitatively and quantitatively. Compared with titration and spectrophotometry, thermal analysis has the advantages of faster analysis speed, less sample consumption, more accuracy, better reproducibility and higher resolution.
7. Application in drug formulation
The formulation of drugs involves many contents, including the stability of raw materials in the formula and whether they would react with each other, the complementarity and enhancement of raw materials in pharmacology, the reduction or control of drug side effects, etc. Using the thermal spectrum curve in thermal analysis technology is the most simple, time-saving and effective method for this research and monitoring.
8. Application in the study of drug dispersion system
The poor water solubility of drugs limits its bioavailability. The solubility of the substance is directly proportional to its surface area. Reducing the drug particles could increase its surface area and then improve its water solubility, so that the drugs could be absorbed by the intestine more effectively. However, the adhesion between small particles makes the drug agglomerate again. Thermal analysis method could disperse one or more active components in inert carrier or medium, so as to make the dispersed phase of drugs, which could improve the stability of small particle drugs.
9. Application in the study of thermal stability and thermal decomposition kinetics of drugs
The stability of drugs, especially thermal stability, is an important factor affecting the storage validity of drugs. The pyrolysis curve of drugs can be determined by thermal analysis, and the thermal decomposition function could be determined by differential method or integral method, then the thermal decomposition reaction could be inferred, and the thermal decomposition kinetic parameters such as activation energy of thermal decomposition reaction could be calculated, so as to deduce the storage validity period of drugs..
10. Application in enantiomers and racemases
Some chemical drugs contain asymmetric structures, thus showing two asymmetric enantiomers. One of them has strong pharmacological activity and can be used for treatment, while the other has weak activity and is an impurity in the former. The purpose of thermal analysis is to find the solid-state characteristics of enantiomers and racemases, and establish the curves of binary systems.
11. Application in tablet disintegration
The determination of disintegration time of drug tablets is one of the important methods to evaluate the quality of tablets. Thermal analysis can accurately determine the time required for the tablet components to reach the maximum surface area and the incomplete dissolution of the powder after the disintegration, and identify each stage of the tablet disintegration and physical change process.
With the development of thermal analysis technology and the establishment of microcomputer database of thermal analysis method, the application field of thermal analysis method in drug research will continue to expand.