Combined use of DSC, TGA, XDR and NIR in the compatibility study of preformulation mixtures for the development of 10 mg tablets of Rupatadine Fumarate
It is essential to guarantee physico-chemical compatibility between the active pharmaceutical ingredient (API) and the components that are planned to be used in the development of a pharmaceutical formulation. A successful compatibility study allows to distinguish between the excipients that can be used and those that may represent a risk in the quality, safety and efficacy of the medication. The present study focuses on the identification of possible incompatibilities between Rupatadine fumarate and the excipients of three formulation prototypes for the development of APIÂ´s 10 mg tablets. Samples of each raw material, placebos and preformulation mixtures were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XDR) and infrared spectroscopy (IRS). The results obtained were analyzed and contrasted with the literature. Based on these, it is demonstrated that the excipients used along with the API do not generate problems in terms of compatibility, as there are no chemical changes in the drug.
Keywords: Active pharmaceutical ingredient, Chemical incompatibility, Compatibility study, Differential scanning calorimetry, Infrared spectroscopy, Preformulation powder mixtures, Rupatadine fumarate, Thermal analysis, Thermogravimetric analysis, X ray diffraction.
2. Orfe, Y. (2014). Estudio de compatibilidad G0/excipientes mediante mÃ©todos isotÃ©rmicos y no isotÃ©rmicos. Santa Clara: Universidad Central "Marta Abreu" de las Villas.
3. Gibson M. Pharmaceutical preformulation and formulation. 2a ed. New York: Informa healthcare; 2009. â€¨
4. Cabeza Zabala, L. Y., & Rojas Camargo, A. P. (2014). Estudio Comparativo de TecnologÃa DSC e Infrarrojo en la IdentificaciÃ³n de Posibles Incompatibilidades en Mezclas Binarias Activo-Excipiente. BogotÃ¡: Universidad de Ciencia y TecnologÃa.
5. Brown M, Antunes E, Glass B. DSC Screening of Potencial Prochlorperazine-excipiente Interactions in Preformulation Studies. Journal of Thermal Analysis and Calorimetry. 1999; 56:1317-1322.
6. Venkataram S, Khohlokwane M, Wallis S. Differential Scanning Calorimetry as a Quick Scanning Technique for Solid State Stability Studies. Drug Development and Industrial Pharmacy. 1995; 21(7):847-855.
7. Duarte F, Soares C, Accioly T, Nervo F. Compatibility study between chlorpropamide and excipients in their physical mixtures. Journal of Thermal Analysis and Calorimetry. 2009; 97(1):355-357.
8. Santamarta R. CaracterizaciÃ³n de aleaciones base Ni-Ti producidas por solidificaciÃ³n rÃ¡pida (melt-spinning), Palma: Universitat de les illesbalears, 2001.
9. Mazurek E, Winnicka K, Czajkowska A. Application of Diferential Scanning Calorimetry in Evaluation of Solid State Interactions in Tablets Containing Acetaminophen. Acta Poloniae Pharmaceutica. 2013; 70(5):787-793.
10. Uriach, J. & CompaÃ±Ãa S.A. 8-cloro-11-(1-((5-metil-3-piridil)metil)-4-piperidiliden)6,11-dihidro-5H-benzo-(5,6)cicloheptal(1,2-b)piridina, fumarato. EspaÃ±a; ES 2 087 818, 2017.
11. Zhuhai Jin Hong Pharmaceutical. One kind of fumaric rupatadine compounds, their synthesis and pharmaceutical compositions thereof. China; CN103804357 B, 2016.
12. AusPAR Rupafin Rupatadine iNova Pharmaceuticals (Australia) Pty Ltd PM-2009-03232-3-5.
13. Billah, M., Egan, R., Ganguly, A., Green, M. Discovery and Preliminary Pharmacology of Sch 37370, a Dual Antagonist of PAF and Histamine. In: Baumann W, ed. by. Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids. 12th ed. New Jersey: AOCS Press; 1991. p. 1172-1174.
14. Castillo L, Madrigal G, Vargas R, Carazo G. Identification of Rupatadine fumarate polymorphic crystalline forms in pharmaceutical raw materials. Asian Journal of Science and Technology. 2018; 1(2):7482-7487.
15. Bio-Pharmaceutical. Rupatadine Fumarate A crystal form and preparation method thereof. China; CN106188008 A, 2016.
16. Pyramides G, Robinson J, Zito W. The combined use of DSC and TGA for the thermal analysis of atenolol tablets. Journal of Pharmaceutical & Biomedical Analysis. 1995; 13(2):103-110.
17. Djefel D, Makhlouf S. Experimental study of the thermal properties of composite stearic acid / coffee grounds / graphite for thermal energy storage. ACMA. 2014; 1-8.
18. Zeleznak K, Hoseney R. The Glass Transition in Starch. Cereal Chem. 1986; 64(2):121-124.
19. Brittain H, Blaine R. Î±-Monohydrate Phase in Lactose by DSC. TA. 2014;:1-3.
20. Dvrn B, Bhavani N, Haarika B. Formulation Development and in Vitro Evaluation of Orally Disintegrating Tablets Containing Rizatriptan Benzoate. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2015;6(1):300-311.
21. Fitzpatrick S, McCabe J, Petts C, Booth S. Effect of moisture on polyvinylpyrrolidone in accelerated stability testing. International Journal of Pharmaceutics. 2002; 246:143-151.
22. Haines P. Thermal Methods of Analysis. Dordrecht: Springer Netherlands; 1995.
23. Listiohadi Y, Hourigan J, Sleigh R, Steele R. Thermal analysis of amorphous lactose and Î±-lactose monohydrate. Dairy Science and Technology. 2008; 89(1):43-67.
24. Ren S, Sun X, Lei T, Wu Q. The Effect of Chemical and High-Pressure Homogenization Treatment Conditions on the Morphology of Cellulose Nanoparticles. Journal of Nanomaterials. 2014; 2014:1-11.
25. Souza S, AraÃºjo E, Morais F. Determination of calcium in tablets containing calcium citrate using thermogravimetry (TG). Braz J Therm Anal. 2013; 2(1):17-22.
26. SmithKline Beecham Corporation. High Druf Load Inmediate and Modified Release Oral Dosage Formulations and Processes for their Manufacture. USA; US 6,558,699 B2, 2003.
27. Chavakula R, Narayana M, Vijaya M. Spectral characterization of rupatadine fumarate and its potential impurities. OCAIJ. 2013; 9(4):143-147.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).