Dissolution Enhancement by Bio-Inspired Mesocrystals: The Study of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate
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The aim of this paper is to enhance the dissolution rate of racemic (R,S)-(±)-sodium ibuprofen dihydrate via a bio-inspired method of growing mesocrystals.
Materials and Methods
Mesocrystals of racemic (R,S)-(±)-sodium ibuprofen dihydrate were successfully prepared from a supersaturated aqueous solution of racemic (R,S)-(±)-sodium ibuprofen dihydrate having the initial degree of supersaturation, S 0 , of 1.326 and the initial saturated concentration, C*, of 0.986 mol/l at 25°C with sodium dodecyl sulfate (SDS) at a concentration of 0.10 g/l. Dynamic light scattering, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and optical microscopy with cross polarizers were employed to understand the formation mechanism and to characterize the superstructures of the SDS generated mesocrystals.
The SDS generated mesocrystals were the assembly of the oriented attachment of racemic (R,S)-(±)-sodium ibuprofen dihydrate nano-sized platelets under the mediation of the side-to-side interaction between SDS and racemic (R,S)-(±)-sodium ibuprofen dihydrate. The SDS generated mesocrystals contained a mixture of the racemic compounds in α- and β-forms and the resolved racemic conglomerate in γ-form with no detectable amount of SDS. The dissolution rate of the SDS generated mesocrystals was more rapid than the one of its counterpart made by conventional crystallization pathway.
The crystallization of racemic (R,S)-(±)-sodium ibuprofen dihydrate in the presence of SDS yielded well-faceted, well-separated, but almost perfectly three-dimensionally aligned nano-sized platelets. This kind of bio-inspired mesocrystal superstructure has definitely opened a new doorway for crystal engineering and pre-formulation design in pharmaceutical industry. The future work is to study the mesocrystal formation of some other active pharmaceutical ingredients in organic solvent systems and to develop an efficient method for screening the additives.
Key wordsbirefringence dissolution rate mesocrystals racemic (R,S)-(±)-sodium ibuprofen dihydrate sodium dodecyl sulfate
This work was supported by a grant from the National Science Council of Taiwan, Republic of China (NSC 95-2113-M-008-012-MY2). Assistance from Ms. Jui-Mei Huang in DSC, Ms. Shew-Jen Weng in PXRD, and Ms. Ching-Tien Lin for SEM and EDS, and all with the Precision Instrument Center and High Valued Instrument Center at National Central University are gratefully acknowledged. We also thank the assistance from Ms. Yi-Yin Lai in DLS with Molecular BioEngineering Laboratory, and my four other students, Mr. Hsiang-Yu Hsieh, Mr. Yeh-Wen Wang, Mr. Hung-Ju Hou, and Mr. Yan-Chan Su in collecting SEM, DLS and dissolution data.
- 1.L. J. Sellars. Special report: Executive prophecies—pharmaceuticals in the new millennium. Pharm. Exec. 60–72 (January 2002).Google Scholar
- 2.Ö. Almarsson, and M. J. Zaworotko. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines. Chem. Commun. 17:1889–1896 (2004).Google Scholar
- 3.Trends in the Pharmaceutical Industry. www.patheon.com/overview/trends.html.
- 7.R. Hilfiker, J. Berghausen, F. Blatter, A. Burkhard, S. M. De Paul, B. Freiermuth, A. Geoffroy, U. Hofmeier, C. Marcolli, B. Siebenhaar, M. Szelagiewicz, A. Vit, and M. von Raumer. Polymorphism – Integrated approach from high-throughput screening to crystallization optimization. J. Therm. Anal. Calor 73(2):429–440 (2003).CrossRefGoogle Scholar
- 11.P. Vishweshwar, J. A. McMahon, M. L. Peterson, M. B. Hickey, T. R. Shattock, and M. J. Zaworotko. Crystal engineering of pharmaceutical co-crystals from polymorphic active pharmaceutical ingredients. Chem. Commun. 36:4601–4603 (2005).Google Scholar
- 12.S. L. Morissette, Ö. Almarsson, M. L. Peterson, J. F. Remenar, M. J. Read, A. V. Lemmo, S. Ellis, M. J. Cima, and C. R. Gardner. High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Adv. Drug Deliv. Rev 56(3):275–300 (2004).PubMedCrossRefGoogle Scholar
- 15.A. M. Thayer. Form and Function. C&EN, 17–30 (June 18 2007).Google Scholar
- 17.T. Lee, and J. Lee. Drug-carrier screening on a chip. Pharm. Tech 27(1):40–48 (2003).Google Scholar
- 19.S. X. Yin, M. Franchini, J. Chen, A. Hsieh, S. Jen, T. Lee, M. Hussain, and R. Smith. Bioavailability enhancement of a COX-2 inhibitor, BMS-347070, from a nanocrystalline dispersion prepared by spray-drying. J. Pharm. Sci. 94(7):1598–1607.Google Scholar
- 21.P. Van Arnum. Nanotechnology advances in drug delivery. Pharm. Tech 31(6):48–52 (2007).Google Scholar
- 28.C.-M. Chun. Hydrothermal crystallization of barium titanate: mechanisms of nucleation and growth. Ph. D. Dissertation, Department of Geosciences, Princeton University, June 1997.Google Scholar
- 31.B. J. Armitage, J. F. Lampard, and A. Smith. Composition of S-Sodium ibuprofen. US Patent 6,242,000 B1 (2001).Google Scholar
- 33.Y. Zhang, and D. J. W. Grant. Similarity in structures of racemic and enantiomeric ibuprofen sodium dihydrates. Acta Cryst. C61(9):m435–m438 (2005).Google Scholar
- 35.S. Behn. Sodium lauryl sulfate. In A. Wade, and P. J. Weller (eds.), Handbook of Pharmaceutical Excipients, 2American Pharmaceutical Association, Washington, USA, 1994, pp. 448–450.Google Scholar
- 42.H. P. Klug, and L. E. Alexander. Crystallite size and lattice strains from line broadening. Chapter 9 in X-ray Diffraction Procedures, 2nd ed., Wiley, New York, 1974, pp. 657–661.Google Scholar