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AAPS PharmSciTech. 2002 February; 3(4): 17.
Published online 2002 September 20. doi:  10.1208/pt030429
PMCID: PMC2751337

Crystal doping aided by rapid expansion of supercritical solutions

Abstract

The purpose of this study was to test the utility of rapid expansion of supercritical solution (RESS) based cocrystallizations in inducing polymorph conversion and crystal disruption of chlorpropamide (CPD). CPD crystals were recrystallized by the RESS process utilizing supercritical carbon dioxide as the solvent. The supercritical region investigated for solute extraction ranged from 45 to 100°C and 2000 to 8000 psi. While pure solute recrystallization formed stage I of these studies, stage II involved recrystallization of CPD in the presence of urea (model impurity). The composition, morphology, and crystallinity of the particles thus produced were characterized utilizing techniques such as microscopy, thermal analysis, x-ray powder diffractometry, and high-performance liquid chromatography. Also, comparative evaluation between RESS and evaporative crystallization from liquid solvents was performed. RESS recrystallizations of commercially available CPD (form A) resulted in polymorph conversion to metastable forms C and V, depending on the temperature and pressure of the recrystallizing solvent. Cocrystallization studies revealed the formation of eutectic mixtures and solid solutions of CPD+urea. Formation of the solid solutions resulted in the crystal disruption of CPD and subsequent amorphous conversion at urea levels higher than 40% wt/wt. Consistent with these results were the reductions in melting point (up to 9°C) and in the ΔHfvalues of CPD (up to 50%). Scanning electron microscopy revealed a particle size reduction of up to an order of magnitude upon RESS processing. Unlike RESS, recrystallizations from liquid organic solvents lacked the ability to affect polymorphic conversions. Also, the incorporation of urea into the lattice of CPD was found to be inadequate. In providing the ability to control both the particle and crystal morphologies of active pharmaceutical ingredients, RESS proved potentially advantageous to crystal engineering. Rapid crystallization kinetics were found vital in making RESS-based doping superior to conventional solvent-based cocrystallizations.

Keywords: Rapid expansion of supercritical solutions, RESS, crystal doping, cocrystallization, chlorpropamide, urea

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Selected References

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1. Cram DJ. The design of molecular hosts, guests and their complexes. Science. 1988;240:760–767. doi: 10.1126/science.3283937. [PubMed] [Cross Ref]
2. Klarner FG, Panitzky J, Blaser D, Boese R. Synthesis and supramolecular structures of molecular chips. Tetrahedron. 2001;57:3673–3687. doi: 10.1016/S0040-4020(01)00230-7. [Cross Ref]
3. Weissbuch I, Leiserowitz L, Lahav M. Tailor-made additives and impurities. In: Mersmann A, editor. Crystallization Technology Handbook. 2nd ed. New York, NY: Marcel Dekker; 2001. pp. 563–616.
4. Williams-Seton L, Davey RJ, Lieberman HF, Pritchard RG. Disorder and twinning in molecular crystals: impurity-induced effects in adipic acid. J Pharm Sci. 2000;89(3):346–354. doi: 10.1002/(SICI)1520-6017(200003)89:3<346::AID-JPS6>3.0.CO;2-I. [PubMed] [Cross Ref]
5. Addadi L. Resolution of conglomerates with the assistance of tailor-made impurities: generality and mechanistic aspects of the “Rule of reversal —a new method for assignment of absolute configuration. J Am Chem Soc. 1982;104:4610–4617. doi: 10.1021/ja00381a018. [Cross Ref]
6. Jane Li Z, Grant DJW. Effects of excess enantiomer on the crystal properties of a racemic compound: ephedrinium 2-naphthalenesulfonate crystals. Int J Pharm. 1996;137:21–31. doi: 10.1016/0378-5173(96)89588-3. [Cross Ref]
7. Davey RJ, Blagden N, Potts GD, Docherty R. Polymorphism in molecular crystals: stabilization of a metastable form by conformational mimicry. J Am Chem Soc. 1997;119(7):1767–1772. doi: 10.1021/ja9626345. [Cross Ref]
8. Gu CH, Chatterjee K, Young V, Grant DJW. Stabilization of a metastable polymorph of sulfamerazine by structurally-related additives. AAPS PharmSci. 2001;3(3).
9. Lemieux RP, Dinescu L. Compounds and methods for doping liquid crystal hosts. US Patent 5 989 451. Issued 11-23-1999.
10. Chow AHL, Hsia CK, Gordon JD, Young JWM, Vargha-Butler EI. Assessment of wettability and its relationship to the intrinsic dissolution rate of doped phenytoin crystals. Int J Pharm. 1995;126:21–28. doi: 10.1016/0378-5173(95)04060-9. [Cross Ref]
11. Prasad KVR, Ristic RI, Sheen DB, Sherwood JN. Crystallization of paracetamol from solution in the presence and absence of impurity. Int J Pharm. 2001;215:29–44. doi: 10.1016/S0378-5173(00)00653-0. [PubMed] [Cross Ref]
12. Weissbuch I, Addadi L, Lahav M, Leiserowitz L. Molecular recognition at crystal interfaces. Science. 1991;253:637–645. doi: 10.1126/science.253.5020.637. [PubMed] [Cross Ref]
13. Burger A. Zur Polymorphie oraler Antidiabetika. Sci Pharm. 1975;43:152–161.
14. Aal-Saieq SS, Riley GS. Polymorphism in sulfonylurea hypoglycemic agents, II: chlorpropamide. Pharm Acta Helv. 1982;57(1):8–11.
15. Simmons DL, Ranz RJ, Gyanchandani D. Polymorphism in pharmaceuticals, III: Chlorpropamide. Can J Pharm Sci. 1973;8(4):125–127.
16. De Villiers MM, Wurster DE. Isothermal interconversion of chlorpropamide polymorphs kinetically quantified by XRPD, diffuse reflectance FTIR and isoperibol solution calorimetry. Acta Pharm. 1999;49:79–88.
17. Mohamed RS, Halverson DS, Debenedetti PG, Prudhomme RK. Solids formation after the expansion of supercritical mixtures. In: Johnston KP, Penninger JML, editors. Supercritical Fluid Science and Technology. Washington, DC: American Chemical Society; 1989. pp. 355–378.
18. Debenedetti PG, Tom JW, Kwauk X, Yeo SD. Rapid expansion of supercritical solutions (RESS): fundamentals and applications. Fluid Phase Equil. 1993;82:311–321. doi: 10.1016/0378-3812(93)87155-T. [Cross Ref]
19. Turk M. Formation of small organic particles by RESS: experimental and theoretical investigations. J Supercrit Fluids. 1999;15:79–89. doi: 10.1016/S0896-8446(98)00131-4. [Cross Ref]
20. Burt HM, Mitchell AG. Crystal defects and dissolution. Int J Pharm. 1981;9:137–152. doi: 10.1016/0378-5173(81)90007-7. [Cross Ref]
21. Hyatt JA. Liquid and supercritical carbon dioxide as organic solvents. J Org Chem. 1984;49:5097–5101. doi: 10.1021/jo00200a016. [Cross Ref]
22. Dandge DK, Heller JP, Wilson KV. Structure solubility correlations: organic compounds and dense carbon dioxide binary systems. Indus Eng Chem Prod Res Dev. 1985;24:162–166. doi: 10.1021/i300017a030. [Cross Ref]
23. Dobbs JM, Wong JM, Lahiere RJ, Johnston KP. Modification of supercritical fluid phase behavior using polar cosolvents. Indus Eng Chem Res. 1987;26:56–65. doi: 10.1021/ie00061a011. [Cross Ref]
24. Yu L. Inferring thermodynamic stability relationship of polymorphs from melting data. J Pharm Sci. 1995;84(8):966–974. doi: 10.1002/jps.2600840812. [PubMed] [Cross Ref]
25. Behme RJ, Brooke D. Heat of fusion measurement of a low melting polymorph of carbamazepine that undergoes multiple phase changes during DSC. J Pharm Sci. 1991;80(10):986–990. doi: 10.1002/jps.2600801016. [PubMed] [Cross Ref]
26. Yoshihashi Y, Kitano H, Yonemochi E, Tereda K. Quantitative correlation between initial dissolution rate and heat of fusion of drug substances. Int J Pharm. 2000;204:1–6. doi: 10.1016/S0378-5173(00)00446-4. [PubMed] [Cross Ref]
27. Otsuka M, Matsumoto T, Higuchi S, Otsuka K, Kaneniwa N. Effects of compression temperature on the consolidation mechanism of chlorpropamide polymorphs. J Pharm Sci. 1995;84(5):614–618. doi: 10.1002/jps.2600840517. [PubMed] [Cross Ref]
28. Ford JL, Rubinstein MH. Phase equilibria and stability characteristics of chlorpropamide-urea solid dispersions. J Pharm Pharmacol. 1977;29:209–211. [PubMed]
29. Koo CH, Cho SI, Yeon YH. The crystal and molecular structure of chlorpropamide. Arch Pharm Res. 1980;3(1):37–49. doi: 10.1007/BF02884759. [Cross Ref]

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