Journal of Thermal Analysis and Calorimetry

, Volume 111, Issue 3, pp 2195–2202 | Cite as

Fast-scan vs conventional differential scanning calorimetry (DSC) techniques in detection of crystallization events of tolbutamide–polyethylene glycol composite

  • N. Musa
  • T. W. Wong


This study investigated the capacity of fast-scan (400 °C min−1) against conventional (10 °C min−1) differential scanning calorimetry (DSC) techniques to track crystallization phenomenon in tolbutamide–polyethylene glycol 3000 composites prepared by hot melt method (mass ratios 1:1, 1:5, and 1:9) and stored at 25 and 75 % relative humidities. Drug crystallization in composites was indicated by X-ray diffractometry (XRD) and scanning electron microscopy characterization over 40 days storage. With reference to XRD as gold measurement standard, fast-scan DSC could not map the crystallization events of composites (Pearson correlation: fast-scan DSC peak temperature and enthalpy versus XRD peak intensity and area, p > 0.05). Conventional DSC was able to indicate marked drug crystallization through an increase in endothermic enthalpy value of peaks at high temperature regimes between 250 and 360 °C due to formation of high melting point crystal form.


Crystallization DSC Polyethylene glycol Tolbutamide 



The authors wish to express their heart-felt thanks to Ministry of Higher Education (0141903), Ministry of Science, Technology and Innovation, and National Science Foundation, Malaysia for financial and facility support given throughout the research study.


  1. 1.
    Bartsch S, Griesser U. Physicochemical properties of the binary system glibenclamide and polyethylene glycol 4000. J Therm Anal Calorim. 2004;77:555–69.CrossRefGoogle Scholar
  2. 2.
    Jorgensen AC, Torstenson AS. Humid storage conditions increase the dissolution rate of diazepam from solid dispersions prepared by melt agglomeration. Pharm Dev Technol. 2008;13:187–95.CrossRefGoogle Scholar
  3. 3.
    Otsuka M, Ofusa T, Matsuda Y. Effect of environmental humidity on the transformation pathway of carbamazepine polymorphic modifications during grinding. Colloids Surf B. 1999;13:263–73.CrossRefGoogle Scholar
  4. 4.
    Windbergs M, Strachan C, Kleinebudde P. Investigating the principles of recrystallization from glyceride melts. AAPS PharmSciTech. 2009;10:1224–33.CrossRefGoogle Scholar
  5. 5.
    Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, Higaki K, Kimura T. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm. 2003;267:79–91.CrossRefGoogle Scholar
  6. 6.
    Roumeli E, Tsiapranta A, Pavlidou E, Vourlias G, Kachrimanis K, Bikiaris D, Chrissafis K. Compatibility study between trandolapril and natural excipients used in solid dosage forms. J Therm Anal Calorim. doi: 10.1007/s10973-012-2476-2.
  7. 7.
    Kaza L, Sobhi HF, Fruscella JA, Kaul C, Thakur S, Perera NI, Alexander K, Riga AT. Thermal analysis of water and magnesium hydroxide content in commercial pharmaceutical suspensions milk of magnesia. J Therm Anal Calorim. doi: 10.1007/s10973-012-2429-9.
  8. 8.
    Maheswaram MP, Mantheni D, Perera I, Venumuddala H, Riga A, Alexander K. Characterization of crystalline and amorphous content in pharmaceutical solids by dielectric thermal analysis. J Therm Anal Calorim. doi: 10.1007/s10973-011-2140-2.
  9. 9.
    Costa RSD, Negrao CAB, Camelo SRP, Ribeiro-Costa RM, Barbosa WLR, Costa CEFD, Junior JOCS. Investigation of thermal behavior of Heliotropium indicum L. lyophilized extract by TG and DSC. J Therm Anal Calorim. doi: 10.1007/s10973-011-2088-2.
  10. 10.
    Nurulaini H, Wong TW. Design of in-situ dispersible and calcium crosslinked alginate pellets as intestinal-specific drug carrier by melt pelletization technique. J Pharm Sci. 2011;100(6):2248–57.CrossRefGoogle Scholar
  11. 11.
    Nor Khaizan A, Wong TW, Taib MN. Microwave modified non-crosslinked pectin films with modulated drug release. Pharm Dev Technol. 2012;17(1):110–7.CrossRefGoogle Scholar
  12. 12.
    Yoshida MI, Oliveira MA, Gomes ECL, Mussel WN, Castro WV, Soares CDV. Thermal characterization of lovastatin in pharmaceutical formulations. J Therm Anal Calorim. 2011;106:657–64.CrossRefGoogle Scholar
  13. 13.
    Azevedo JR, Sizilio RH, Brito MB, Costa AMB, Serafini MR, Araújo AAS, Santos MRV, Lira AAM, Nunes RS. Physical and chemical characterization insulin-loaded chitosan-TPP nanoparticles. J Therm Anal Calorim. 2011;106:685–9.CrossRefGoogle Scholar
  14. 14.
    Patyi G, Bódis A, Antal I, Vajna B. Nagy Zs, Marosi Gy, Thermal and spectroscopic analysis of inclusion complex of spironolactone prepared by evaporation and hot melt methods. J Therm Anal Calorim. 2010;102:349–55.CrossRefGoogle Scholar
  15. 15.
    ShimarizaAshikin WHN, Wong TW, Law CL. Plasticity of hot air-dried mannuronate- and guluronate-rich alginate films. Carbohydr Polym. 2010;81:104–13.CrossRefGoogle Scholar
  16. 16.
    Gaisford S. Fast-scan differential scanning calorimetry. Eur Pharm Rev. 2008;4:83–9.Google Scholar
  17. 17.
    Pijpers M, Mathot V. Optimization of instrument response and resolution of standard- and high-speed power compensation DSC. J Therm Anal Calorim. 2008;93:319–27.CrossRefGoogle Scholar
  18. 18.
    Lappalainen M, Karppinen M. Techniques of differential scanning calorimetry for quantification of low contents of amorphous phases. J Therm Anal Calorim. 2010;102:171–80.CrossRefGoogle Scholar
  19. 19.
    Buckton G, Adeniyi AA, Saunders M, Ambarkhane A. HyperDSC studies of amorphous polyvinylpyrrolidone in a model wet granulation system. Int J Pharm. 2006;312:61–5.CrossRefGoogle Scholar
  20. 20.
    Liu P, Yu L, Liu H, Chen L, Li L. Glass transition temperature of starch studied by a high-speed DSC. Carbohydr Polym. 2009;77:250–3.CrossRefGoogle Scholar
  21. 21.
    Saunders M, Podluii K, Shergill S, Buckton G, Royall P. The potential of high speed DSC (hyper-DSC) for the detection and quantification of small amounts of amorphous content in predominantly crystalline samples. Int J Pharm. 2004;274:35–40.CrossRefGoogle Scholar
  22. 22.
    Gramaglia D, Conway BR, Kett VL, Malcolm RK, Batchelor HK. High speed DSC (hyper-DSC) as a tool to measure the solubility of a drug within a solid or semi-solid matrix. Int J Pharm. 2005;301:1–5.CrossRefGoogle Scholar
  23. 23.
    McGregor C, Saunders MH, Buckton G, Saklatvala RD. The use of high-speed differential scanning calorimetry (hyper-DSC) to study the thermal properties of carbamazepine polymorphs. Thermochim Acta. 2004;417:231–7.CrossRefGoogle Scholar
  24. 24.
    McGregor C, Bines E. The use of high-speed differential scanning calorimetry (hyper-DSC) in the study of pharmaceutical polymorphs. Int J Pharm. 2008;350:48–52.CrossRefGoogle Scholar
  25. 25.
    Zhang GGZ, Law D, Schmitt EA, Qiu Y. Phase transformation considerations during process development and manufacture of solid oral dosage forms. Adv Drug Deliv Rev. 2004;56:371–90.CrossRefGoogle Scholar
  26. 26.
    Singh D, Rawat MSM, Semalty A, Semalty M. Chrysophanol-phospholipid complex: a drug delivery strategy in herbal novel drug delivery system (HNDDS). J Therm Anal Calorim. doi: 10.1007/s10973-012-2448-6.
  27. 27.
    Damian F, Blaton N, Kinget R, Van den Mooter G. Physical stability of solid dispersions of the antiviral agent UC-781 with PEG 6000, Gelucire® 44/14 and PVP K30. Int J Pharm. 2002;244:87–98.CrossRefGoogle Scholar
  28. 28.
    Chakravarty P, Alexander KS, Riga AT, Chatterjee K. Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure. Int J Pharm. 2005;288:335–48.CrossRefGoogle Scholar
  29. 29.
    Hasegawa G, Komasaka T, Bando R, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H, Terada K. Reevaluation of solubility of tolbutamide and polymorphic transformation from Form I to unknown crystal form. Int J Pharm. 2009;369:12.CrossRefGoogle Scholar
  30. 30.
    Zografi G. States of water associated with solids. Drug Dev Ind Pharm. 1988;14:1905–26.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2012

Authors and Affiliations

  1. 1.Particle Design Research Group, Faculty of PharmacyUniversiti Teknologi MARAPuncak AlamMalaysia
  2. 2.Non-Destructive Biomedical and Pharmaceutical Research CentreUniversiti Teknologi MARAPuncak AlamMalaysia

Personalised recommendations