Skip to main content

Advertisement

SpringerLink
Log in

Mixing method influence on compatibility and polymorphism studies by DSC and statistical analysis

Application to tenofovir disoproxil fumarate

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

Most of the pharmaceutical products are formulated as solid dosage form, which may present drug–excipient interactions that lead to changes in the chemical nature of the drug, such as solubility and bioavailability and may compromise its safety and effectiveness. Differential scanning calorimetry (DSC) is a widely used method for the rapid evaluation of the drug-excipient compatibility and the stability of the mixture formed; however, there is no consensus on the preparation methods of the drug–excipient mixtures. The aim of this study was to investigate the influence of the mixing method on the drug–excipient compatibility studies by means of DSC analysis, using tenofovir disoproxil fumarate as a drug model. Statistical analysis revealed significant differences in the heat of fusion of the drug in the mixtures prepared by several mixing methods. Vortex Mixer with a Pop-Off Cup used for 3 min proved to be very satisfactory for these studies. A polymorphic transition was observed in the mixture prepared with the mortar and pestle. Therefore, this method should be avoided since it may induce errors in the interpretation of DSC results. In this way, the mixing method used to prepare a mixture for studies of interactions between the API and the excipients in a pharmaceutical formulation has a great influence on the results and it must be chosen carefully.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tishmack PA, Bugay DE, Byrn SR. Solid-state nuclear magnetic resonance spectroscopy–pharmaceutical applications. J Pharm Sci. 2003;92:441–74.

    Article  CAS  Google Scholar 

  2. Pani NR, Nath LK, Acharya S, Bhuniya B. Application of DSC, IST, and FTIR study in the compatibility testing of nateglinide with different pharmaceutical excipients. J Therm Anal Calorim. 2012;108:219–26.

    Article  CAS  Google Scholar 

  3. Tonder ECV, Lotter AP, Botha SA. Compatibility study between Doxylamine Succinate with other Drugs. Drug Dev Ind Pharm. 1990;16:2125–33.

    Article  Google Scholar 

  4. Dias SBT, Nascimento TG, Santos AFO, Viana IMMN, Almeida RM, Júnior IDB, Macêdo RO, Araújo-Júnior JX. Polymorphic characterization and compatibility study of clozapine: implications on its stability and some biopharmaceutics properties. J Therm Anal Calorim. 2015;120:795–805.

    Article  CAS  Google Scholar 

  5. Matos APS, Costa JS, Boniatti J, Seiceira RC, Pitaluga Junior A, Oliveira DL, Viçosa AL, Holandino C. Compatibility study between diazepam and tablet excipientes. J Therm Anal Calorim. 2016;127:1675–82.

    Article  Google Scholar 

  6. Bernardi LS, Oliveira PR, Murakami FS, Silva MAS, Borgmann SHM, Cardoso SG. Characterization of venlafaxine hydrochloride and compatibility studies with pharmaceutical excipients. J Therm Anal Calorim. 2009;97:729–33.

    Article  CAS  Google Scholar 

  7. Peterka TR, Grahek R, Hren J, Bastarda A, Bergles J, Urleb U. Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation. J Pharm Biomed Anal. 2015;110:67–75.

    Article  Google Scholar 

  8. Veronez IP, Daniel SP, Garcia JS, Trevisan MG. Characterization and compatibility study of desloratadine. J Therm Anal Calorim. 2014;115:2407–14.

    Article  CAS  Google Scholar 

  9. Teleginski LK, Maciel AB, Mendes C, Silva MAS, Bernardi LS, Oliveira PR. Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver. J Therm Anal Calorim. 2015;120:771–81.

    Article  CAS  Google Scholar 

  10. Jurca T, Tita D, Fulias A, Marian E, Tita B. Compatibility study of the acetylsalicylic acid with different solid dosage forms excipients. J Therm Anal Calorim. 2013;112:407–19.

    Article  Google Scholar 

  11. Tita B, Fulias A, Szabadai Z, Rusu G, Bandur G, Tita D. Compatibility study between ibuprofen and excipients in their binary mixtures. J Therm Anal Calorim. 2011;105:517–27.

    Article  CAS  Google Scholar 

  12. Tita B, Ledeti I, Bandur G, Tita D. Compatibility study between indomethacin and excipients in their physical mixtures. J Therm Anal Calorim. 2014;118:1293–304.

    Article  CAS  Google Scholar 

  13. Tita B, Fulias A, Bandur G, Marian E, Tita D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. J Pharm Biomed Anal. 2011;56:221–7.

    Article  CAS  Google Scholar 

  14. Lima IPB, Lima NGPB, Barros DMC, Oliveira TS, Barbosa EG, Gomes APB, Ferrari M, Nascimento TG, Aragão CFS. Compatibility study of tretinoin with several pharmaceutical excipients by thermal and non-thermal techniques. J Therm Anal Calorim. 2015;120:733–47.

    Article  CAS  Google Scholar 

  15. Lima IPB, Lima NGPB, Barros DMC, Oliveira TS, Mendonça CMS, Barbosa EG, Raffin FN, Lima e Moura TFA, Gomes APB, Ferrari M, Aragão CFS. Compatibility study between hydroquinone and the excipients used in semi-solid pharmaceutical forms by thermal and non-thermal techniques. J Therm Anal Calorim. 2015;120:719–32.

    Article  Google Scholar 

  16. Rojek B, Wesolowski M. Fourier transform infrared spectroscopy supported by multivariate statistics in compatibility study of atenolol with excipients. Vib Spectrosc. 2016;86:190–7.

    Article  CAS  Google Scholar 

  17. Gao R, Jin Y, Yang QY, Sun BW, Lin J. Study of stability and drug-excipient compatibility of estradiol and pharmaceutical excipients. J Therm Anal Calorim. 2015;120:839–45.

    Article  CAS  Google Scholar 

  18. Chaves LL, Rolim LA, Gonçalves MLCM, Vieira ACC, Alves LDS, Soares MFR, Soares-Sobrinho JL, Lima MCA, Rolim-Neto PJ. Study of stability and drug-excipient compatibility of diethylcarbamazine citrate. J Therm Anal Calorim. 2013;111:2179–86.

    Article  CAS  Google Scholar 

  19. Matos APS, Costa JS, Boniatti J, Seiceira RC, Pitaluga A Jr, Oliveira DL, Viçosa AL, Holandino C. Compatibility study between diazepam and tablet excipients. J Therm Anal Calorim. 2017;127:1675–82.

    Article  CAS  Google Scholar 

  20. Lee EH, Smith DT, Fanwick PE, Byrn SR. Characterization and anisotropic lattice expansion/contraction of polymorphs of tenofovir disoproxil fumarate. Cryst Growth Des. 2010;10:2314–22.

    Article  CAS  Google Scholar 

  21. Gomes ECL, Mussel WN, Resende JM, Fialho SL, Barbosa J, Carignani E, Geppi M, Yoshida MI. Characterization of Tenofovir Disoproxil Fumarate and Its Behavior under Heating. Cryst Growth Des. 2015;15:1915–22.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to CNPq, CAPES, FAPEMIG and PRPq/UFMG for providing financial assistance.

Author information

Authors and Affiliations

  1. Chemistry Department, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Elionai Cassiana de Lima Gomes & Maria Irene Yoshida

  2. Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Izabella Ercole de Carvalho & Armando da Silva Cunha Júnior

  3. Ezequiel Dias Foundation (FUNED), Belo Horizonte, MG, 30510-010, Brazil

    Silvia Ligório Fialho & Jamile Barbosa

Authors
  1. Elionai Cassiana de Lima Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Izabella Ercole de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Ligório Fialho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jamile Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Irene Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Armando da Silva Cunha Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elionai Cassiana de Lima Gomes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10973_2017_6827_MOESM1_ESM.docx

Supplementary Information (DSC curves of the mixtures between tenofovir disoproxil fumarate and starch submitted to different mixing methods M3, M4, M5 and M6) is available free of charge

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Lima Gomes, E.C., Ercole de Carvalho, I., Fialho, S.L. et al. Mixing method influence on compatibility and polymorphism studies by DSC and statistical analysis. J Therm Anal Calorim 131, 2123–2128 (2018). https://doi.org/10.1007/s10973-017-6827-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-017-6827-x

Keywords

Search

Navigation