Skip to main content
PMC home page
AAPS PharmSciTech logoLink to AAPS PharmSciTech
. 2003 Jan 9;4(1):33–41. doi: 10.1208/pt040105

Effect of surface modification on hydration kinetics of carbamazepine anhydrate using isothermal microcalorimetry

Makoto Otsuka 1,✉, Mika Ishii 1, Yoshihisa Matsuda 1
PMCID: PMC2750301  PMID: 12916915

Abstract

The purpose of this research was to improve the stability of carbamazepine (CBZ) bulk powder under high humidity by surface modification. The surface-modified anhydrates of CBZ were obtained in a specially designed surface modification apparatus at 60°C via the adsorption of n-butanol, and powder x-ray diffraction, Fourier-Transformed Infrared spectra, and differential scanning calorimetry were used to determine the crystalline characteristics of the samples. The hydration process of intact and surface-modified CBZ anhydrate at 97% relative humidity (RH) and 40±1°C was automatically monitored by using isothermal microcalorimetry (IMC). The dissolution test for surface-modified samples (20 mg) was performed in 900 mL of distilled water at 37±0.5°C with stirring by a paddle at 100 rpm as in the Japanese Pharmacopoeia XIII. The heat flow profiles of hydration of intact and surface-modified CBZ anhydrates at 97% RH by using IMC profiles showed a maximum peak at around 10 hours and 45 hours after 0 and 10 hours of induction, respectively. The result indicated that hydration of CBZ anhydrate was completely inhibited at the initial stage by surface modification of n-butanol and thereafter transformed into dihydrate. The hydration of surface-modified samples followed a 2-dimensional phase boundary process with an induction period (IP). The IP of intact and surface-modified samples decreased with increase of the reaction temperature, and the hydration rate constant (k) increased with increase of the temperature. The crystal growth rate constants of nuclei of the intact sample were significantly larger than the surface-modified samples at each temperature. The activation energy (E) of nuclei formation and crystal growth process for hydration of surface-modified CBZ anhydrate were evaluated to be 20.1 and 32.5 kJ/mol, respectively, from Arrhenius plots, but the Es of intact anhydrate were 56.3 and 26.8 kJ/mol, respectively. The dissolution profiles showed that the surface-modified sample dissolved faster than the intact sample at the initial stage. The dissolution kinetics were analyzed based on the Hixon-Crowell equation, and the dissolution rate constants for intact and surface-modified anhydrates were found to be 0.0102±0.008 mg1/3 min−1 and 0.1442±0.0482 mg1/3·min−1. The surface-modified anhydrate powders were more stable than the nonmodified samples under high humidity and showed resistance against moisture. However, surface modification induced rapid dissolution in water compared to the control.

Keywords: carbamazepine, anhydrate, surface modification, stability, hydration kinetic analysis, dissolution kinetics

Full Text

The Full Text of this article is available as a PDF (123.8 KB).

References

  • 1.FDA papers. Guidelines: manufacturing and controls for INDs and NDAs. Pharm Tech Japan. 1985;1:835–850.
  • 2.Haleblian JK. Characterization of habits and crystalline modification of solids and their pharmaceutical applications. J Pharm Sci. 1975;64:1269–1288. doi: 10.1002/jps.2600640805. [DOI] [PubMed] [Google Scholar]
  • 3.Otsuka M, Matsuda Y. Polymorphism, pharmaceutical aspects. In: Swarbrick J, Boylan JC, editors. Encyclopedia of Pharmaceutical Technology. Vol 12. New York, NY: Marcel Dekker; 1995. pp. 305–326. [Google Scholar]
  • 4.Stephenson GA, Stowell JG, Toma PH, Pfeiffer RR, Byrn SR. Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity. J Pharm Sci. 1997;86:1239–1244. doi: 10.1021/js9701667. [DOI] [PubMed] [Google Scholar]
  • 5.Campen V, Amidon GL, Zografi G. Moisture sorption kinetics for water-soluble substances, III: theoretical and experimental studies in air. J Pharm Sci. 1983;72:1394–1408. doi: 10.1002/jps.2600721206. [DOI] [PubMed] [Google Scholar]
  • 6.Campen V, Amidon GL, Zografi G. Moisture sorption kinetics for water-soluble substances, II: experimental verification of heat transport control. J Pharm Sci. 1983;72:1388–1393. doi: 10.1002/jps.2600721205. [DOI] [PubMed] [Google Scholar]
  • 7.Kontny MJ, Zografi G. Moisture sorption kinetics for water-soluble substances, IV: studies with mixtures of solids. J Pharm Sci. 1983;74:124–127. doi: 10.1002/jps.2600740204. [DOI] [PubMed] [Google Scholar]
  • 8.Vadas EB, Toma P, Zografi G. Solid-state phase-transitions initiated by water vapor sorption of crystalline L-660, 711, a leukotriene D4 receptor antagonist. Pharm Res. 1991;8:148–155. doi: 10.1023/A:1015871415925. [DOI] [PubMed] [Google Scholar]
  • 9.Nightingale SL. From the Food and Drug Administration. JAMA. 1990;263:1896–1896. doi: 10.1001/jama.263.14.1896. [DOI] [PubMed] [Google Scholar]
  • 10.Briggner L, Buckton G, Bystrom K, Darcy P. The use of isothermal microcalorimetry in the study of changes in crystallinity induced during the processing of powders. Int J Pharm. 1994;105:125–135. doi: 10.1016/0378-5173(94)90458-8. [DOI] [Google Scholar]
  • 11.Sebhatu T, Angberg M, Ahlneck C. Assessment of the degree of disorder in crystalline solids by isothermal microcalorimetry. Int J Pharm. 1994;104:135–144. doi: 10.1016/0378-5173(94)90188-0. [DOI] [Google Scholar]
  • 12.Angberg M, Nyström C, Castensson S. Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies, V: a new approach for continuous measurements in abundant water vapour. Int J Pharm. 1992;81:153–167. doi: 10.1016/0378-5173(92)90007-O. [DOI] [Google Scholar]
  • 13.Sheridan PL, Buckton G, Storey DE. Development of a flow microcalorimetry method for the assessment of surface properties of powders. Pharm Res. 1995;12:1025–1030. doi: 10.1023/A:1016262531972. [DOI] [PubMed] [Google Scholar]
  • 14.Buckton G, Darcy P, Greenleaf D, Holbrook P. The use of isothermal microcalorimetry in the study of changes in crystallinity of spray-dried salbutamol sulphate. Int J Pharm. 1995;116:113–118. doi: 10.1016/0378-5173(94)00322-V. [DOI] [Google Scholar]
  • 15.Aso Y, Yoshioka S, Otsuka T, Kojima S. The physical stability of amorphous nifedipine determined by isothermal microcalorimetry. Chem Pharm Bull. 1995;43:300–303. [Google Scholar]
  • 16.Rat M, Guillaume P, Wilker S, Pantel G. Practical application of microcalorimetry to the stability of propellants. Workshop Microcalorim Energ Mater. 1997; V1–V18.
  • 17.Mimura H, Kitamura S, Koda S. Evaluation of drug stability by isothermal microcalorimetry. Netsu Sokutei. 1998;25(4):92–96. [Google Scholar]
  • 18.Giron D. Thermal analysis, microcalorimetry, and combined techniques for the study of pharmaceuticals. J Therm Anal Calorim. 1999;56(3):1285–1304. doi: 10.1023/A:1010194020563. [DOI] [Google Scholar]
  • 19.Du W, Li X, Wang B, Zhang Y. A study on the interaction between cisplatin and urease. Thermochim Acta. 1999;333(2):109–114. doi: 10.1016/S0040-6031(99)00115-X. [DOI] [Google Scholar]
  • 20.Beezer A, Gaisford S, Hills AK, Mitchell JC. Pharmaceutical microcalorimetry: applications to long-term stability studies. Int J Pharm. 1999;179(2):159–165. doi: 10.1016/S0378-5173(98)00336-6. [DOI] [PubMed] [Google Scholar]
  • 21.Runge FE, Heger R. Use of microcalorimetry in monitoring stability. Example: vitamin A esters. J Agric Food Chem. 2000;48(1):47–55. doi: 10.1021/jf981163y. [DOI] [PubMed] [Google Scholar]
  • 22.Tompa AS, Bryant WF Jr. Microcalorimetry and DSC study of the compatibility of energetic materials. Workshop Microcalorim Energ Mater. 1999;Q1–Q21.
  • 23.Phipps MA, Mackin LA. Application of isothermal calorimetry in solid state drug development. Pharm Sci Technol Today. 2000;3(1):9–17. doi: 10.1016/S1461-5347(99)00227-8. [DOI] [PubMed] [Google Scholar]
  • 24.Otsuka M, Ishii M, Matsuda Y. Effect of surface-modification on hydration kinetics of nitrofurantoin anhydrate. Colloids and Surfaces B: Biointerfaces. 2002;23:73–82. doi: 10.1016/S0927-7765(01)00210-7. [DOI] [Google Scholar]
  • 25.Kaneniwa N, Yamaguchi T, Watari N, Otsuka M. Hygroscopicity of carbamazepine crystalline powders [in Japanese] Yakugaku Zasshi. 1984;104:184–190. doi: 10.1248/yakushi1947.104.2_184. [DOI] [PubMed] [Google Scholar]
  • 26.Kaneniwa N, Ichikawa J, Yamaguchi T, Hayashi K, Watari N, Sumi M. Dissolution behaviour of carbamazepine polymorphs. Yakugaku Zasshi. 1987;107(10):808–813. doi: 10.1248/yakushi1947.107.10_808. [DOI] [PubMed] [Google Scholar]
  • 27.Hixon A, Crowell J. Dependent of reaction velocity upon surface and agitation. Ind Eng Chem. 1931;23:923–923. doi: 10.1021/ie50260a018. [DOI] [Google Scholar]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists

RESOURCES