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AAPS PharmSciTech. 2006 September; 7(3): E70–E73.
Published online 2006 August 4. doi:  10.1208/pt070365
PMCID: PMC2750507

Estimation of intramolecular cyclization activation energies via isothermal gravimetric analysis: A technical note

Summary and Conclusion

Isothermal gravimetric analysis was used to monitor the weight loss of 4 exploratory compounds as an indicator of their solid-state thermal stability. Data obtained from TGA were further processed via a model-free isoconversional method to estimate the activation energy values. These values ranged from 140 to 218 kJ/mol and were inversely related to their corresponding surface areas. Based on their activation energy values, the relative stability of these 4 exploratory compounds can be ranked as C>D>B>A and their formulation development activities can be prioritized.

Keywords: isothermal analysis, thermogravimetric analysis, isoconversional model, intramolecular cyclization, model-free kinetics

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Guo Y, Byrn SR, Zografi G. Physical characteristics and chemical degradation of amorphous quinapril hydrochloride. J. Pharm Sci. 2000;89:128–143. doi: 10.1002/(SICI)1520-6017(200001)89:1<128::AID-JPS13>3.0.CO;2-Z. [PubMed] [Cross Ref]
2. Strickley RG, Visor GC, Lin H-H, Gu L. An unexpected pH effect on the stability of moexipril lyophilized powder. Pharm Res. 1989;6:971–975. doi: 10.1023/A:1015901731275. [PubMed] [Cross Ref]
3. Leung SS, Grant DJ. Solid state stability studies of model dipeptides: aspartame and aspartylphenylalanine. J Pharm Sci. 1997;86:64–71. doi: 10.1021/js960228d. [PubMed] [Cross Ref]
4. Lin SY, Cheng YD. Simultaneous formation and detection of the reaction product of solid-state aspartame sweetener by FT-IR/DSC microscopic system. Food Addit Contam. 2000;17:821–827. doi: 10.1080/026520300420385. [PubMed] [Cross Ref]
5. Wang SL, Lin SY, Chen TF. Thermal-dependent dehydration process and intramolecular cyclization of lisinopril dihydrate in the solid state. Chem Pharm Bull (Tokyo) 2000;48:1890–1893. [PubMed]
6. Lin SY, Wang SL, Chen TF, Hu TC. Intramolecular cyclization of diketopiperazine formation in solid-state enalapril maleate studied by thermal FT-IR microscopic system. Eur J Pharm Biopharm. 2002;54:249–254. doi: 10.1016/S0939-6411(02)00053-X. [PubMed] [Cross Ref]
7. Wang SL, Lin SY, Chen TF. Reaction kinetics of solid-state cyclization of enalapril maleate investigated by isothermal FT-IR microscopic system. Chem Pharm Bull (Tokyo) 2001;49:402–406. doi: 10.1248/cpb.49.402. [PubMed] [Cross Ref]
8. Vecchio S, Rodante F, Tomassetti M. Thermal stability of disodium and calcium phosphomycin and the effects of the excipients evaluated by thermal analysis. J Pharm Biomed Anal. 2001;24:1111–1123. doi: 10.1016/S0731-7085(00)00568-9. [PubMed] [Cross Ref]
9. Huang Y, Cheng Y, Alexander K, Dollimore D. The thermal analysis study of the drug captopril. Thermochim Acta. 2001;367–368:43–58. doi: 10.1016/S0040-6031(00)00687-0. [Cross Ref]
10. Dollimore D, O’Connell C. A comparison of the thermal decomposition of preservatives, using thermogravimetry and rising temperature kinetics. Thermochim Acta. 1998;324:33–48. doi: 10.1016/S0040-6031(98)00521-8. [Cross Ref]
11. Halikia I, Neou-Syngouna P, Kolitsa D. Isothermal kinetic analysis of the thermal decomposition of magnesium hydroxide using thermogravimetric data. Thermochim Acta. 1998;320:75–88. doi: 10.1016/S0040-6031(98)00413-4. [Cross Ref]
12. Keuleers RR, Janssens JF, Desseyn HO. Comparison of some methods for activation energy determination of thermal decomposition reactions by thermogravimetry. Thermochim. Acta. 2002;385:127–142. doi: 10.1016/S0040-6031(01)00720-1. [Cross Ref]
13. Miller JM, Kale UJ, Lau SM, Greene L, Wang HY. Rapid estimation of kinetic parameters for thermal decomposition of penicillins by modulated thermogravimetric analysis. J. Pharm Biomed Anal. 2004;35:65–73. doi: 10.1016/j.jpba.2004.01.007. [PubMed] [Cross Ref]
14. Vyazovkin S, Wight CA. Isothermal and nonisothermal reaction kinetics in solid: in search of ways toward consensus. J Phys Chem. 1997;101:8279–8284.
15. Vyazovkin S, Wight CA. Model-free and model-fitting approaches to kinetic analysis of isothermal and nonisothermal data. Thermochim Acta. 1999;340–341:53–68. doi: 10.1016/S0040-6031(99)00253-1. [Cross Ref]
16. Rodante F, Vecchio S, Tomassetti M. Kinetic analysis of thermal decomposition for penicillin sodium salts: model-fitting and model-free methods. J Pharm Biomed. Anal. 2002;29:1031–1043. doi: 10.1016/S0731-7085(02)00144-9. [PubMed] [Cross Ref]
17. Zhou D, Schmitt EA, Zhang GG, et al. Crystallization kinetics of amorphous nifedipine studied by model-fitting and model-free approaches. J Pharm Sci. 2003;92:1779–1792. doi: 10.1002/jps.10425. [PubMed] [Cross Ref]
18. Zhu H, Grant DJ. Dehydration behavior, of nedocromil magnesium pentahydrate. Int J Pharm. 2001;215:251–262. doi: 10.1016/S0378-5173(00)00700-6. [PubMed] [Cross Ref]
19. Vyazovkin S, Wight CA. Ammonium dinitramide: kinetics and mechanism of thermal decomposition. J Phys Chem. 1997;101:5653–5658.

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