Investigation of the Multi-Step Dehydration Reaction of Theophylline Monohydrate Using 2-Dimensional Powder X-ray Diffractometry
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
(i) To study the dehydration kinetics of theophylline monohydrate using 2-dimensional (2D) powder X-ray diffractometry (XRD), and (ii) to investigate the effect of polyvinylpyrrolidone (PVP) on the dehydration pathway and kinetics.
Theophylline monohydrate (C7H8N4O2·H2O; M) was recrystallized from aqueous PVP solutions of different concentrations. Dehydration kinetics was studied isothermally, at several temperatures, from 35 to 130°C. The experimental set-up comprised of a high intensity X-ray source (synchrotron radiation or 8 kW rotating anode), a heating chamber, and a 2D area detector. Diffraction patterns were collected continuously, with a time resolution ranging from 40 ms to 30 s, over the angular range of 3 to 27°2θ.
Dehydration of M resulted in either the stable (C7H8N4O2; A), or the metastable anhydrate (A*), with the latter having a tendency to transform to A. The XRD technique allowed simultaneous quantification of M, A* and A during the dehydration reaction. The rate constants for individual reaction steps (M→A*; M→A and A*→A) were determined by fitting the data to solid-state reaction models. In presence of PVP, there was a decrease in the magnitude of the rate constant associated with the M→A transition, resulting in an increased build-up of A* in the product. The inhibitory effect of PVP on M→A transition was more pronounced at lower dehydration temperatures, and was proportional to the concentration of PVP.
Two dimensional powder X-ray diffractometry, using a high intensity source, is a powerful technique to study kinetics of rapid solid-state reactions. The inhibitory effect of excipients can have profound effect on phases formed during pharmaceutical processing.
- D. J. Sutor. The structures of the pyrimidines and purines. VI. The crystal structure of theophylline. Acta Crystallogr. 11:83–87 (1958). CrossRef
- C. Sun, D. Zhou, D. J. W. Grant, and V. G. Young, Jr. Theophylline monohydrate. Acta Crystallogr. E58:368–370 (2002).
- A. A. Naqvi and G. C. Bhattacharyya. Crystal data for anhydrous theophylline. J. Appl. Crystallogr. 14:464 (1981). CrossRef
- C. Agbada and P. York. Dehydration of theophylline monohydrate powder: effects of particle size and sample weight. Int. J. Pharm. 106:33–40 (1994). CrossRef
- C. T. Lin and S. R. Byrn. Desolvations of solvated organic crystals. Molr. Cryst. Liq. Cryst. 50:99–104 (1979).
- M. Otsuka, N. Kaneniwa, K. Kawakami, and O. Umezawa. Effect of surface characteristics of theophylline anhydrate powder on hygroscopic stability. J. Pharm. Pharmacol. 42:606–610 (1990).
- M. Otsuka, N. Kaneniwa, K. Kawakami, and O. Umezawa. Effects of tableting pressure on hydration kinetics of theophylline anhydrate tablets. J. Pharm. Pharmacol. 43:226–231 (1991).
- E. Shefter, H.-L. Fung, and O. Mok. Dehydration of crystalline theophylline monohydrate and ampicillin trihydrate. J. Pharm. Sci. 62:791–794 (1973).
- E. Suihko, J. Ketolainen, A. Poso, M. Ahhlgren, J. Gynther, and P. Paronen. Dehydration of theophylline monohydrate—a two step process. Int. J. Pharm. 158:47–55 (1997). CrossRef
- S. P. Duddu, N. G. Das, T. P. Kelly, and T. D. Sokoloski. Microcalorimetric investigation of phase transitions. I. Is water desorption from theophylline.HOH a single-step process? Int. J. Pharm. 114:247–256 (1995). CrossRef
- M. T. Ledwidge and O. I. Corrigan. Effects of environmental factors on the dehydration of diclofenac HEP dihydrate and theophylline monohydrate. Int. J. Pharm. 147:41–49 (1997). CrossRef
- N. V. Phadnis and R. Suryanarayanan. Polymorphism in anhydrous theophylline—implications for the dissolution rate of theophylline tablets. J. Pharm. Sci. 86:1256–1263 (1997). CrossRef
- E. Suihko, V. P. Lehto, J. Ketolainen, E. Laine, and P. Paronen. Dynamic solid-state and tableting properties of four theophylline forms. Int. J. Pharm. 217:225–236 (2001). CrossRef
- ICH (International Conference on Harmonisation). Draft guidance on Q6A specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. Federal Register 65(251):83041–83063 (2000).
- Process analytical technology—a framework for innovative pharmaceutical manufacturing and quality assurance. Draft guidance. U.S. Department of Health and Human Services. Food and Drug Administration. Federal Register 68(172):52781–52782 (2003).
- K. R. Morris, U. J. Griesser, C. J. Eckhardt, and J. G. Stowell. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes. Adv. Drug Deliv. Rev. 48:91–114 (2001). CrossRef
- S. Byrn, R. Pfeiffer, M. Ganey, C. Hoiberg, and G. Poochikian. Pharmaceutical solids: a strategic approach to regulatory considerations. Pharm. Res. 12:945–954 (1995). CrossRef
- S. R. Byrn, W. Xu, and A. W. Newman. Chemical reactivity in solid-state pharmaceuticals: formulation implications. Adv. Drug Deliv. Rev. 48:115–136 (2001). CrossRef
- S. K. Rastogi, M. Zakrzewski, and R. Suryanarayanan. Investigation of solid-state reactions using variable temperature X-ray powder diffractometry. II. Aminophylline monohydrate. Pharm. Res. 19:1265–1273 (2002). CrossRef
- D. Giron. Thermal analysis and calorimetric methods in the characterization of polymorphs and solvates. Themochim. Acta 348:1–59 (1995). CrossRef
- D. Giron. Characterization of pharmaceuticals by thermal analysis. Am. Pharm. Rev. 3:53–54, 56, 58–61 (2000).
- H. P. Klug and L. E. Alexander. X-ray Diffraction Procedures for Polycrystalline and Amorphous Materials. Wiley, New York, 1974.
- R. Suryanarayanan. X-ray powder diffractometry. In H. G. Brittain (ed.), Physical Characterization of Pharmaceutial Solids, Marcel Dekker, New York, 1995, pp. 187–221.
- M. Otsuka, N. Kaneniwa, K. Otsuka, K. Kawakami, and O. Umezawa. Effect of tableting pressure and geometrical factor of tablet on dehydration kinetics of theophylline monohydrate tablets. Drug Dev. Ind. Pharm. 19:541–557 (1993).
- M. Karjalainen, S. Airaksinen, J. Rantanen, J. Aaltonen, and J. Yliruusi. Characterization of polymorphic solid-state changes using variable temparature X-ray powder diffraction. J. Pharm. Biomed. Anal. 39:27–32 (2005). CrossRef
- S. Airaksinen, M. Karjalainen, E. Rasanen, J. Rantanen, and J. Yliruusi. Comparison of the effects of two drying methods on polymorphism of theophylline. Int. J. Pharm. 276:129–141 (2004). CrossRef
- J. Tank. Changes in Solid-State of Theophylline upon Wet Granulation, M.S. dissertation, Department of Pharmaceutics, University of Minnesota, 1997.
- M. Yoshioka, B. C. Hancock, and G. Zografi. Inhibition of indomethacin crystallization in poly(vinylpyrrolidone) coprecipitates. J. Pharm. Sci. 84:983–986 (1995).
- R. L. Larkin and R. E. Kupel. Quantitative analysis of poly(vinylpyrrolidinone) atmosphere samples and biological tissues. Am. Ind. Hyg. Assoc. J. 26:558–561 (1965).
- G. B. Levy and D. Fergus. Microdetermination of polyvinylpyrrolidone in aqueous solution and in body fluids. Anal. Chem. 25:1408–1410 (1953). CrossRef
- M. Savva, V. P. Torchilin, and L. Huang. Effect of polyvinylpyrrolidone on the thermal phase transition of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayer. J. Colloid Interface Sci. 217:160–165 (1999). CrossRef
- C. Nunes. Use of High-Intensity X-radiation in Solid-State Characterization of Pharmaceuticals, Ph.D. dissertation, Department of Pharmaceutics, University of Minnesota, 2005.
- C. Nunes, A. Mahendrasingam, and R. Suryanarayanan. Quantification of crystallinity in substantially amorphous materials by synchrotron X-ray powder diffractometry. Pharm. Res. 22:1942–1953 (2005). CrossRef
- Powder Diffraction File-2. International Centre for Diffraction Data. Newtown Square, Pennsylvania, 1996.
- J. H. Sharp, G. W. Brindley, and B. N. N. Achar. Numerical data for some commonly used solid state reaction equations. J. Am. Ceram. Soc. 49:379–382 (1966). CrossRef
- D. C. Monkhouse and L. Van Campen. Solid state reactions—theoretical and experimental aspects. Drug Dev. Ind. Pharm. 10:1175–1276 (1984).
- E. Suzuki, K. Shimomura, and K. Sekiguchi. Thermochemical study of theophylline and its hydrate. Chem. Pharm. Bull. 37:493–497 (1989).
- W. J. Dunning. Theory of crystal nucleation from vapour, liquid and solid systems. In W. E. Garner (ed.), Chemistry of the Solid State, Academic, New York, 1955, pp. 159–183.
- Y. V. Mnyukh. Molecular mechanism of polymorphic transitions. Molr. Cryst. Liq. Cryst. 52:467–503 (1979).
- Y. V. Mnyukh. Polymorphic transitions in crystals: Nucleation. J. Cryst. Growth 32:371–377 (1976). CrossRef
- Y. V. Mnyukh and N. N. Petropavlov. Polymorphic transitions in molecular crystals. I. Orientations of lattices and interfaces. J. Phys. Chem. Solids 33:2079–2087 (1972).
- F. C. Tompkins. Decomposition reactions. In N. B. Hannay (ed.), Reactivity of Solids, Plenum, New York, 1976, pp. 193–232.
- H. Schmalzried. Solid-state reactions. In N. B. Hannay (ed.), Reactivity of Solids, Plenum, New York, 1976, pp. 233–280.
- A. K. Galwey. The reactivity of solids in thermal decomposition (crystolysis) reactions. In V. V. Boldyrev (ed.), Reactivity of Solids: Past, Present and Future, Blackwell Science, Malden, Massachusetts, 1996, pp. 15–42.
- L. S. Taylor and G. Zografi. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm. Res. 14:1691–1698 (1997). CrossRef
- K. Khougaz and S.-D. Clas. Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. J. Pharm. Sci. 89:1325–1334 (2000). CrossRef
- T. Matsumoto and G. Zografi. Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm. Res. 16:1722–1728 (1999). CrossRef
- E. D. L. Smith, R. B. Hammond, M. J. Jones, K. J. Roberts, J. B. O. Mitchell, S. L. Price, R. K. Harris, D. C. Apperley, J. C. Cherryman, and R. Docherty. The determination of the crystal structure of anhydrous theophylline by X-ray powder diffraction with a systematic search algorithm, lattice energy calculations, and 13C and 15N solid-state NMR: a question of polymorphism in a given unit cell. J. Phys. Chem. B. 105:5818–5826 (2001). CrossRef
- Investigation of the Multi-Step Dehydration Reaction of Theophylline Monohydrate Using 2-Dimensional Powder X-ray Diffractometry
Volume 23, Issue 10 , pp 2393-2404
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- theophylline monohydrate
- X-ray diffraction
- Industry Sectors
- Author Affiliations
- 1. Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455, USA
- 2. Pharmaceutics R&D, Bristol Myers Squibb Company, New Brunswick, New Jersey, 08903, USA
- 3. Department of Physics, Keele University, Staffordshire, ST5-5BG, UK