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Effect of Small Levels of Impurities on the Water Vapor Sorption Behavior of Ranitidine HCl

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Abstract

Purpose

Deliquescence is the process by which a solid undergoes dissolution by sorbing moisture from its surroundings when a characteristic relative humidity, RH0, is reached. For mixtures of two or more deliquescent solids, RH0 will generally be lowered. The goal of this research was to investigate the effect of small amounts of impurities or degradants on RH0 for a model deliquescent pharmaceutical salt.

Materials and Methods

The model salt chosen for this work was ranitidine HCl, which has two polymorphic forms. Moisture sorption profiles for each polymorph and samples of different purities were obtained using a gravimetric water vapor sorption balance.

Results

Polymorphs of a similar purity yielded virtually identical moisture sorption profiles. In contrast, samples containing higher levels of impurities had both enhanced moisture sorption below RH0 and a lowered value of RH0.

Conclusions

It was concluded that small levels of degradants and/or impurities can drastically affect the moisture sorption profile of a deliquescent material, both through affecting the deliquescence relative humidity and by altering the overall interaction of the substance with moisture. Such changes in behavior may have significant effects on both active pharmaceutical ingredient and drug product stability during both processing and storage.

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References

  1. J. T. Carstensen, A. Gerhardt, T. Morris, and F. Nikfar. Effect of moisture on solid dosage forms—can the Arrhenius equation be used as a predictor. Drug Dev. Ind. Pharm. 16:2267–2281 (1990).

    CAS  Google Scholar 

  2. C. Ahlneck and G. Zografi. The molecular-basis of moisture effects on the physical and chemical-stability of drugs in the solid-state. Int. J. Pharm. 62:87–95 (1990).

    Article  CAS  Google Scholar 

  3. J. T. Carstensen. Effect of moisture on the stability of solid dosage forms. Drug Dev. Ind. Pharm. 14:1927–1969 (1988).

    CAS  Google Scholar 

  4. J. T. Carstensen, F. Attarchi, and X. P. Hou. Decomposition of aspirin in the solid-state in the presence of limited amounts of moisture. J. Pharm. Sci. 74:741–745 (1985).

    Article  CAS  PubMed  Google Scholar 

  5. S. Yoshioka and M. Uchiyama. Kinetics and mechanism of the solid-state decomposition of propantheline bromide. J. Pharm. Sci. 75:92–96 (1986).

    Article  CAS  PubMed  Google Scholar 

  6. S. Yoshioka, T. Shibazaki, and A. Ejima. Stability of solid dosage forms. 1. Hydrolysis of meclofenoxate hydrochloride in the solid-state. Chem. Pharm. Bull. 30:3734–3741 (1982).

    CAS  Google Scholar 

  7. R. Teraoka, M. Otsuka, and Y. Matsuda. Effects of temperature and relative-humidity on the solid-state chemical-stability of ranitidine hydrochloride. J. Pharm. Sci. 82:601–604 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. K. Uzunarslan and J. Akbuga. The effect of moisture on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques. Drug Dev. Ind. Pharm. 17:1067–1081 (1991).

    CAS  Google Scholar 

  9. K. Uzunarslan and J. Akbuga. Moisture adsorption and effect of adsorbed water on the powder and compaction properties of ranitidine hydrochloride. Pharmazie 46:273–275 (1991).

    CAS  Google Scholar 

  10. G. Zografi. States of water associated with solids. Drug Dev. Ind. Pharm. 14:1905–1926 (1988).

    Article  CAS  Google Scholar 

  11. K. Danjo, H. Kato, A. Otsuka, and T. Wakimoto. Influence of moisture adsorption on volume shrinkage and diametral tensile-strength of sucrose tablets. Chem. Pharm. Bull. 41:2147–2150 (1993).

    CAS  Google Scholar 

  12. M. Otsuka and Y. Matsuda. The effect of humidity on hydration kinetics of mixtures of nitrofurantoin anhydride and diluents. Chem. Pharm. Bull. 42:156–159 (1994).

    CAS  Google Scholar 

  13. A. K. Salameh and L. S. Taylor. Deliquescence in binary mixtures. Pharm. Res. 22:318–324 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. L. Van Campen, G. Zografi, and J. T. Carstensen. An approach to the evaluation of hygroscopicity for pharmaceutical solids. Int. J. Pharm. 5:1–18 (1980).

    Article  CAS  Google Scholar 

  15. M. J. Kontny and G. Zografi. Sorption of water by solids. Drugs Pharm. Sci. 70:387–418 (1995).

    CAS  Google Scholar 

  16. L. Van Campen, G. L. Amidon, and G. Zografi. Moisture sorption kinetics for water-soluble substances. 1. Theoretical considerations of heat-transport control. J. Pharm. Sci. 72:1381–1388 (1983).

    Article  CAS  PubMed  Google Scholar 

  17. S. D. Brooks, M. E. Wise, M. Cushing, and M. A. Tolbert. Deliquescence behavior of organic/ammonium sulfate aerosol. Geophys. Res. Lett. 29:1917–1920 (2002).

    Article  CAS  Google Scholar 

  18. S. L. Clegg, J. H. Seinfeld, and P. Brimblecombe. Thermodynamic modelling of aqueous aerosols containing electrolytes and dissolved organic compounds. J. Aerosol Sci. 32:713–738 (2001).

    Article  CAS  Google Scholar 

  19. J. S. Lin and A. Tabazadeh. The effect of nitric acid uptake on the deliquescence and efflorescence of binary ammoniated salts in the upper troposphere. Geophys. Res. Lett. 29:1488 (2002).

    Article  CAS  Google Scholar 

  20. C. Marcolli, B. P. Luo, and T. Peter. Mixing of the organic aerosol fractions: liquids as the thermodynamically stable phases. J. Phys. Chem. A 108:2216–2224 (2004).

    Article  CAS  Google Scholar 

  21. I. N. Tang, H. R. Munkelwitz, and J. G. Davis. Aerosol growth studies—IV: phase transformation of mixed salt aerosols in a moist atmosphere. J. Aerosol Sci. 9:505–511 (1978).

    Article  CAS  Google Scholar 

  22. N. Beaulieu, P. M. Lacroix, R. W. Sears, and E. G. Lovering. High-performance liquid-chromatographic methods for the determination of ranitidine and related substances in raw-materials and tablets. J. Pharm. Sci. 77:889–892 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. M. B. Evans, P. A. Haywood, D. Johnson, M. Martinsmith, G. Munro, and J. C. Wahlich. Chromatographic methods for determining the identity, strength and purity of ranitidine hydrochloride both in the drug substance and its dosage forms—an exercise in method selection, development, definition and validation. J. Pharm. Biomed. Anal. 7:1–22 (1989).

    Article  CAS  PubMed  Google Scholar 

  24. P. A. Haywood, M. Martinsmith, T. J. Cholerton, and M. B. Evans. Isolation and identification of the hydrolytic degradation products of ranitidine hydrochloride. J. Chem. Soc., Perkin Trans. 1:951–954 (1987).

    Article  Google Scholar 

  25. M. A. Kelly, K. D. Altria, C. Grace, and B. J. Clark. Optimisation, validation and application of a capillary electrophoresis method for the determination of ranitidine hydrochloride and related substances. J. Chromatogr. A 798:297–306 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. H. Nyqvist. Saturated salt solutions for maintaining specified relative humidities. Int. J. Pharm. Technol. Prod. Manuf. 4:47–48 (1983).

    CAS  Google Scholar 

  27. V. Wu, T. Rades, and D. J. Saville. Stability of polymorphic forms of ranitidine hydrochloride. Pharmazie 55:508–512 (2000).

    CAS  PubMed  Google Scholar 

  28. A. K. Salameh, L. J. Mauer, and L. S. Taylor. Deliquescence lowering in food ingredient mixtures. J. Food Sci. 71:E10–E16 (2006).

    Article  CAS  Google Scholar 

  29. I. N. Tang and K. H. Fung. Hydration and Raman scattering studies of levitated microparticles: Ba(NO(3))(2), Sr(NO3)(2), and Ca(NO3)(2). J. Chem. Phys. 106:1653–1660 (1997).

    Article  CAS  Google Scholar 

  30. J. T. Carstensen and M. K. Franchini. Isoenergetic polymorphs. Drug Dev. Ind. Pharm. 21:523–536 (1995).

    CAS  Google Scholar 

  31. B. C. Hancock and G. Zografi. Effects of solid-state processing on water vapor sorption by aspirin. J. Pharm. Sci. 85:246–248 (1996).

    CAS  PubMed  Google Scholar 

  32. R. Saklatvala, P. G. Royall, and D. Q. M. Craig. The detection of amorphous material in a nominally crystalline drug using modulated temperature DSC—a case study. Int. J. Pharm. 192:55–62 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. S. E. Dilworth, G. Buckton, S. Gaisford, and R. Ramos. Approaches to determine the enthalpy of crystallisation, and amorphous content, of lactose from isothermal calorimetric data. Int. J. Pharm. 284:83–94 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. G. H. Ward and R. K. Schultz. Process-induced crystallinity changes in albuterol sulfate and its effect on powder physical stability. Pharm. Res. 12:773–779 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. A. Saleki-Gerhardt, C. Ahlneck, and G. Zografi. Assessment of Disorder in Crystalline Solids. Int. J. Pharm. 101:237–247 (1994).

    Article  CAS  Google Scholar 

  36. T. Luty and C. J. Eckhardt. General theoretical concepts for solid-state reactions—quantitative formulation of the reaction cavity, steric compression, and reaction-induced stress using an elastic multipole representation of chemical pressure. J. Am. Chem. Soc. 117:2441–2452 (1995).

    Article  CAS  Google Scholar 

  37. S. R. Byrn, R. R. Pfeifffer, and J. G. Stowell. Solid-State Chemistry of Drugs, SSCI, West Lafayette, Indiana, 1999.

  38. S. Ghosal and J. C. Hemminger. Surface adsorbed water on NaCl and its effect on nitric acid reactivity with NaCl powders. J. Phys. Chem. B 108:14102–14108 (2004).

    Article  CAS  Google Scholar 

  39. M. Luna, F. Rieutord, N. A. Melman, Q. Dai, and M. Salmeron. Adsorption of water on alkali halide surfaces studied by scanning polarization force microscopy. J. Phys. Chem. A 102:6793–6800 (1998).

    Article  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge AstraZeneca R&D Lund, Sweden for funding this research. Dr Kjell Järring and Dr Frans Langkilde are thanked for helpful comments. Dr. Dan Smith is thanked for providing use of the Agilent 1100 HPLC system. Dr. Karl Wood is thanked for his discussions regarding the LC/MS results.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana, 47907, USA

    Peter Guerrieri, Adnan K. Salameh & Lynne S. Taylor

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  1. Peter Guerrieri
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  2. Adnan K. Salameh
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  3. Lynne S. Taylor
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Correspondence to Lynne S. Taylor.

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Guerrieri, P., Salameh, A.K. & Taylor, L.S. Effect of Small Levels of Impurities on the Water Vapor Sorption Behavior of Ranitidine HCl. Pharm Res 24, 147–156 (2007). https://doi.org/10.1007/s11095-006-9134-y

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  • DOI: https://doi.org/10.1007/s11095-006-9134-y

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