Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions
Pharmaceutical cocrystallization is a useful method to regulate the physical properties of active pharmaceutical ingredients (APIs). Since the cocrystals may form in various API/coformer ratios, identification of the cocrystal composition is the critical first step of any further analysis. However,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/9/2/70 |
| _version_ | 1798000058432487424 |
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| author | Hyunseon An Insil Choi Il Won Kim |
| author_facet | Hyunseon An Insil Choi Il Won Kim |
| author_sort | Hyunseon An |
| collection | DOAJ |
| description | Pharmaceutical cocrystallization is a useful method to regulate the physical properties of active pharmaceutical ingredients (APIs). Since the cocrystals may form in various API/coformer ratios, identification of the cocrystal composition is the critical first step of any further analysis. However, the composition identification is not always unambiguous if cocrystallization is performed in solid state with unsuccessful solution crystallization. Single melting point and some new X-ray diffraction peaks are necessary but not sufficient conditions. In the present study, the use of melting diagrams coupled with the X-ray diffraction data was tested to identify cocrystal compositions. Adefovir dipivoxil (AD) was used as a model API, and succinic acid (SUC), suberic acid (SUB), and glutaric acid (GLU) were coformers. Compositions of AD/SUC and AD/SUB had been previously identified as 2:1 and 1:1, but that of AD/GLU was not unambiguously identified because of the difficulty of solution crystallization. Melting diagrams were constructed with differential scanning calorimetry, and their interpretation was assisted by powder X-ray diffraction. The cocrystal formation was exhibited as new compositions with congruent melting in the phase diagrams. This method correctly indicated the previously known cocrystal compositions of AD/SUC and AD/SUB, and it successfully identified the AD/GLU cocrystal composition as 1:1. The current approach is a simple and useful method to assess the cocrystal compositions when the crystallization is only possible in solid state. |
| first_indexed | 2024-04-11T11:14:13Z |
| format | Article |
| id | doaj.art-8dfcb25de1c543f68a4686f0355dd984 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-04-11T11:14:13Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-8dfcb25de1c543f68a4686f0355dd9842022-12-22T04:27:19ZengMDPI AGCrystals2073-43522019-01-01927010.3390/cryst9020070cryst9020070Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal CompositionsHyunseon An0Insil Choi1Il Won Kim2Department of Chemical Engineering, Soongsil University, Seoul 06978, Republic of KoreaDepartment of Chemical Engineering, Soongsil University, Seoul 06978, Republic of KoreaDepartment of Chemical Engineering, Soongsil University, Seoul 06978, Republic of KoreaPharmaceutical cocrystallization is a useful method to regulate the physical properties of active pharmaceutical ingredients (APIs). Since the cocrystals may form in various API/coformer ratios, identification of the cocrystal composition is the critical first step of any further analysis. However, the composition identification is not always unambiguous if cocrystallization is performed in solid state with unsuccessful solution crystallization. Single melting point and some new X-ray diffraction peaks are necessary but not sufficient conditions. In the present study, the use of melting diagrams coupled with the X-ray diffraction data was tested to identify cocrystal compositions. Adefovir dipivoxil (AD) was used as a model API, and succinic acid (SUC), suberic acid (SUB), and glutaric acid (GLU) were coformers. Compositions of AD/SUC and AD/SUB had been previously identified as 2:1 and 1:1, but that of AD/GLU was not unambiguously identified because of the difficulty of solution crystallization. Melting diagrams were constructed with differential scanning calorimetry, and their interpretation was assisted by powder X-ray diffraction. The cocrystal formation was exhibited as new compositions with congruent melting in the phase diagrams. This method correctly indicated the previously known cocrystal compositions of AD/SUC and AD/SUB, and it successfully identified the AD/GLU cocrystal composition as 1:1. The current approach is a simple and useful method to assess the cocrystal compositions when the crystallization is only possible in solid state.https://www.mdpi.com/2073-4352/9/2/70pharmaceutical cocrystalmelting diagramliquid assisted grindingadefovir dipivoxildicarboxylic acid |
| spellingShingle | Hyunseon An Insil Choi Il Won Kim Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions Crystals pharmaceutical cocrystal melting diagram liquid assisted grinding adefovir dipivoxil dicarboxylic acid |
| title | Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions |
| title_full | Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions |
| title_fullStr | Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions |
| title_full_unstemmed | Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions |
| title_short | Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions |
| title_sort | melting diagrams of adefovir dipivoxil and dicarboxylic acids an approach to assess cocrystal compositions |
| topic | pharmaceutical cocrystal melting diagram liquid assisted grinding adefovir dipivoxil dicarboxylic acid |
| url | https://www.mdpi.com/2073-4352/9/2/70 |
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