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Effect of Counterion on the Solid State Photodegradation Behavior of Prazosin Salts

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Abstract

The effect of counterion was evaluated on the photodegradation behavior of six prazosin salts, viz., prazosin hydrochloride anhydrous, prazosin hydrochloride polyhydrate, prazosin tosylate anhydrous, prazosin tosylate monohydrate, prazosin oxalate dihydrate, and prazosin camsylate anhydrous. The salts were subjected to UV–Visible irradiation in a photostability test chamber for 10 days. The samples were analyzed for chemical changes by a specific stability-indicating high-performance liquid chromatography method. pH of the microenvironment was determined in 10% w/v aqueous slurry of the salts. The observed order of photostability was: prazosin hydrochloride anhydrous > prazosin camsylate anhydrous ∼ prazosin-free base > prazosin hydrochloride polyhydrate > prazosin tosylate anhydrous > prazosin oxalate dihydrate ∼ prazosin tosylate monohydrate. Multivariate analysis of the photodegradation behavior suggested predominant contribution of the state of hydration and also intrinsic photosensitivity of the counterion. Overall, hydrated salts showed higher photodegradation compared to their anhydrous counterparts. Within the anhydrous salts, aromatic and carbonyl counterion-containing salts showed higher susceptibility to light. The pH of microenvironment furthermore contributed to photodegradation of prazosin salts, especially for drug counterions with inherent higher pH. The study reveals importance of selection of a suitable drug salt form for photosensitive drugs during preformulation stage of drug development.

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REFERENCES

  1. Berge S, Bighley L, Monkhouse D. Pharmaceutical salts. J Pharm Sci. 1977;66:1–19.

    Article  CAS  PubMed  Google Scholar 

  2. Black S, Collier E, Davey R, Roberts R. Structure, solubility, screening, and synthesis of molecular salts. J Pharm Sci. 2007;96:1053–68.

    Article  CAS  PubMed  Google Scholar 

  3. Bowker M. A procedure for salt selection and optimization. In: Stahl PH, Wermuth CG, editors. Handbook of pharmaceutical salts: properties, selection and use. Weinheim: Wiley-VCH; 2002. p. 161–89.

    Google Scholar 

  4. Davies G. Changing the salt, changing the drug. Pharm J. 2001;266:322–3.

    Google Scholar 

  5. Gould P. Salt selection for basic drugs. Int J Pharm. 1986;33:201–17.

    Article  CAS  Google Scholar 

  6. Serajuddin A. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59:603–16.

    Article  CAS  PubMed  Google Scholar 

  7. Albini A, Fasani E. Photochemistry of drugs: An overview and practical problems. In: Albini A, Fasani E, editors. Drugs: photochemistry and photostability. Cambridge: Royal Society of Chemistry; 1998. p. 1–65.

    Google Scholar 

  8. Aman W, Thoma K. The influence of formulation and manufacturing process on the photostability of tablets. Int J Pharm. 2002;243:33–41.

    Article  CAS  PubMed  Google Scholar 

  9. Tonnesen H. Formulation and stability testing of photolabile drugs. Int J Pharm. 2001;225:1–14.

    Article  CAS  PubMed  Google Scholar 

  10. Albini A, Fasani E. Photochemistry of drugs: an overview and practical problems. Spec Publ R Soc Chem. 1998;225:1–73.

    CAS  Google Scholar 

  11. Moan J. Benefits and adverse effects from the combination of drugs and light. In: Tonnesen HH, editor. The photostability of drugs and drug formulations. London: Taylor and Francis; 1996. p. 173–88.

    Google Scholar 

  12. Woo J, Chi M, Kim Y, Yi H. Complex formulation comprising amlodipine camsylate and simvastatin and method for preparation therof, Patent No US 2009/0005425 A1 2006.

  13. Nord K, Orsteen A, Karlsen J, Tonnesen H. Pharmazie. 1997;52:8.

    Google Scholar 

  14. Torniainen K, Tammilehto S, Ulvi V. The effect of pH, buffer type and drug concentration on the photodegradation of ciprofloxacin. Int J Pharm. 1996;132:53–61.

    Article  CAS  Google Scholar 

  15. Minipress package insert, http://wwwpfizercom/files/products/uspi_minipresspdf.

  16. Prazosin hydrochloride—monograph, United States Pharmacopeia, USP29NF24.

  17. Bianco E. Novel crystalline forms of prazosin hydrochloride, Patent No 4092315 1978.

  18. Thoma K. Photodecomposition and stabilization of compounds in dosage forms. In: Tonnesen HH, editor. The photostability of drugs and drug formulations. London: Taylor and Francis; 1996. p. 111–40.

    Google Scholar 

  19. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Q1B: Stability testing: photostability testing of new drug substances and products; 1996.

  20. Serajuddin A, Jarowski C. Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical acids and their sodium salts II: salicylic acid, theophylline, and benzoic acid. J Pharm Sci. 1985;74:148–54.

    Article  CAS  PubMed  Google Scholar 

  21. Serajuddin A, Jarowski C. Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical bases and their hydrochloride salts I: phenazopyridine. J Pharm Sci. 1985;74:142–7.

    Article  CAS  PubMed  Google Scholar 

  22. Serajuddin A, Thakur A, Ghoshal R, Fakes M, Ranadive S, Morris K, et al. Selection of solid dosage form composition through drug–excipient compatibility testing. J Pharm Sci. 1999;88:696–704.

    Article  CAS  PubMed  Google Scholar 

  23. Budrugeac P, Segal E. Applicability of the Kissinger equation in thermal analysis. J Therm Anal Calorim. 2007;88:703–7.

    Article  CAS  Google Scholar 

  24. Kissinger H. Reaction kinetics in differential thermal analysis. Anal Chem. 1957;29:1702–6.

    Article  CAS  Google Scholar 

  25. Kumar L, Meena C, Pawar Y, Wahlang B, Jain R, Bansal A. Effect of counterion on the physicochemical properties of prazosin salts. AAPS Pharm Sci Tech. 2013;14:141–50.

    Google Scholar 

  26. Kumar L, Bansal A. Effect of humidity on the hydration behaviour of prazosin hydrochloride polyhydrate: thermal, sorption and crystallographic study. Thermochim Acta. 2011;525:206–10.

    Article  CAS  Google Scholar 

  27. Carstensen J. Stability of solids and solid dosage forms. J Pharm Sci. 1974;63:1–14.

    Article  CAS  PubMed  Google Scholar 

  28. Dotterer R, Allen J. Finding peacable photostability. Pharm Formul Qual. 2006.

  29. Doigan P, Davis T. The photolysis of crystalline nitrates. J Phys Chem. 1952;56:764–6.

    Article  CAS  Google Scholar 

  30. Akimoto K, Inoue K, Sugimoto I. Photostability of several crystal forms of cianidanol. Chem Pharm Bull. 1985;33:4050–3.

    Article  CAS  PubMed  Google Scholar 

  31. Akimoto K, Nakagawa H, Sugimoto I. Photostability of cianidanol in aqueous solution. Drug Dev Ind Pharm. 1985;11:865–89.

    Article  CAS  Google Scholar 

  32. Sheng J, Venkatesh G, Duddu S, Grant D. Dehydration behavior of eprosartan mesylate dihydrate. J Pharm Sci. 1999;88:1021–9.

    Article  CAS  PubMed  Google Scholar 

  33. Ross D, Riley C. Aqueous solubilities of some variously substituted quinolone antimicrobials. Int J Pharm. 1990;63:237–50.

    Article  CAS  Google Scholar 

  34. Tonnesen H, Kristensen S, Nord K. Photoreactivity of selected antimalarial compounds in solution and in the solid state. In: Albini A, Fasani E, editors. Drugs: photochemistry and photostability. Cambridge: Royal Society of Chemistry; 1998. p. 87–115.

    Google Scholar 

  35. Badawy S, Hussain M. Microenvironmental pH modulation in solid dosage forms. J Pharm Sci. 2007;96:948–59.

    Article  CAS  PubMed  Google Scholar 

  36. Torniainen K, Mattinen J, Askolin C, Tammilehto S. Structure elucidation of a photodegradation product of ciprofloxacin. J Pharm Biomed Anal. 1997;15:887–94.

    Article  CAS  PubMed  Google Scholar 

  37. Albini A, Fasani E. Rationalizing the photochemistry of drugs. In: Tonnesen HH, editor. Photostability of drugs and drug formulations. New York: CRC; 2004. p. 67–110.

    Chapter  Google Scholar 

  38. HPV assessment report on para toluenesulfonic acid http://wwwepagov/hpv/pubs/summaries/ptolacid/c16597rspdf Accessed 05 August 2011.

  39. Oxalic acid—material safety data sheet http://wwwchemcasorg/drug/analytical/cas/6153-56-6asp Accessed 05 August 2011.

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ACKNOWLEDGMENTS

Lokesh Kumar acknowledges the Department of Science and Technology, Government of India, and Ranbaxy Science Foundation for providing research fellowship.

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160 062, India

    Lokesh Kumar & Arvind Bansal

  2. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160 062, India

    Rajan Jog & Saranjit Singh

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  1. Lokesh Kumar
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  2. Rajan Jog
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  4. Arvind Bansal
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Correspondence to Arvind Bansal.

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Kumar, L., Jog, R., Singh, S. et al. Effect of Counterion on the Solid State Photodegradation Behavior of Prazosin Salts. AAPS PharmSciTech 14, 757–763 (2013). https://doi.org/10.1208/s12249-013-9961-1

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