Study of in-vitro biotransformation of prodrugs of Ester and Amide linkages of Ibuprofen, Diclofenac Sodium and Paracetamol in acidic and alkaline medium
Keywords:
Prodrug-A/Prodrug-B/Prodrug-C, Ibuprofen, Paracetamol, Diclofenac sodium, Molecular weight, logP, UV λmax, IR, Mobile phase, TLC-Rf value, HPLC-Rt value, LOD, LOC
Abstract
Our goal is to perform in-vitro biotransformation of Prodrugs of ibuprofen+paracetamol, diclofenac sodium+paracetamol and ibuprofen+diclofenac sodium by acidic and alkaline hydrolysis of both ester (–COO–) and amide (–CONH–) linkages into free drugs and chromatographically separation of their Rt in HPLC. Since both ester (–COO–) and amide (–CONH–) linkages are susceptible for hydrolysis in both acidic pH (gastric pH) and basic pH (intestinal pH) to produce parent drug ibuprofen, diclofenac and paracetamol by biotransformation in in-vivo; so it will be implemented as a Prodrug which can show prolong action on pain and fever after getting release into free parent drug by biotransformation. The HPLC (High Performance Liquid Chromatography) study reports the retention time (Rt) and release kinetics of three Prodrugs by taking HPLC degradation datas of three samples of Prodrugs and individual HPLC datas of parent drugs separately to compare the Rt value of release of three drugs from Prodrugs in both acidic and alkaline pH. Prodrug–A (logP=4.56) releases Ibuprofen & Paracetamol, Prodrug–B (logP=4.90) releases Diclofenac & Paracetamol and Prodrug–C (logP=6.13) releases Ibuprofen & Diclofenac. This is a comparison study of drug release in in-vitro gastric as well as intestinal pH focusing on in-vivo biotransformation. Keywords: Prodrug-A/Prodrug-B/Prodrug-C, Ibuprofen, Paracetamol, Diclofenac sodium, Molecular weight, logP, UV λmax, IR, Mobile phase, TLC-Rf value, HPLC-Rt value, LOD, LOC.
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37. Slemmer J.E., Martin B.R., Damaj M.I. Bupropion is a nicotinic antagonist. J. Pharm. Exp. Ther. 2000; 295: 321–327.
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2. Dhrubo Jyoti Sen and Jalpa G. Patel; Logarithmic partition coefficient comparison study and molecular weight of synthesized Prodrugs of ibuprofen+paracetamol, diclofenac sodium+paracetamol and ibuprofen+diclofenac sodium: American Journal of Advanced Drug Delivery: 2016, 4(05), 064-068.
3. J.E. Slemmer, B.R. Martin and M.I. Damaj. Bupropion is a nicotinic antagonist. J. Pharm. Exp. Ther., 2000; 295: 321–327.
4. C. Wu, J. Quan, J. Xie, C Branford-White, L. Zhu, Y. Yu and Y. Wang. Preparation and controlled release of degradable polymeric ketoprofen-saccharide conjugates. Polym Bull., 2011; 67: 593–608.
5. M, Babazadeh and T. Mosanejhad, Vinyl ester type polymers containing ibuprofen pendents: synthesis, characterization and evaluation. Iran Polym J., 2009; 18: 179–186.
6. L. Shargel, Susanna Wu-Pong and B.C. Andrew, Applied Biopharmaceutics & Pharmacokinetics, 6th Ed.McGraw-Hill Medical Publishing Division, US., 2012; 47-66, 129-154.
7. S. Shirke*, S. Shewale and M. Satpute, Prodrug design: an overview. International Journal of Pharmaceutical, Chemical and Biological Sciences., 2015; 5(1): 232-241.
8. A.V. Bhosale, G.P. Agrawal and P.Mishra: Preparation and Evaluation of Directly Compressible Forms of Mutual Prodrugs of Ibuprofen Forms of Mutual Prodrugs of Ibuprofen. Indian Journal of Pharmaceutical Sciences, 2006; 68(4): 425-431.
9. Beckett AH and Stenlake JB, Practice pharmaceutical chemistry; 4th Edn; CBS Publishers and Distributors, New Delhi, 1997, 293-304.
10. Ewing GW, Instrumental Methods of Chemical Analysis; 5th Edn; McGraw- Hill Book Company, New York, 1985, 1-7.
11. Kasture AV, Mahadik KR, Wadodkar SG and More HN, Instrumental methods of pharmaceutical analysis; 14th Edn; Nirali Prakashan, Pune, 2006, 1-30.
12. Wikipedia: The free Encyclopedia, “Ultraviolet-visible spectroscopy”, 2013, https://en.wikipedia.org/wiki/Ultraviolet-visible spectroscopy.
13. Davidson AG, Practical Pharmaceutical Chemistry; 4th Edn; CBS Publishers and Distributors, 1997, 275-337.
14. Skoog DA, Holler FJ and Nieman TA, Principle of Instrumentation Analysis; 5th Edn; Thomas Asia Pvt Ltd, 2005, 580.
15. Sharma BK, Instrumental Method of Chemical Analysis; 25th Edn; Krishna Prakashan Media Ltd, 2006, 183-186.
16. Beckett AH and Stenlake JB, Practical Pharmaceutical Chemistry; 4th Edn; CBC Publication and distribution, 1977, 1-26.
17. Snyder LR., Kirkland JL and Glajch JL., Practical HPLC Method Development.,2nd Edition, Wiley Interscience, 1977, 1- 26.
18. Halmilton RJ and Sewell PA., Introduction to HPLC., 2nd Edition; Chapman and Hall, 1982, 189.
19. Stability Testing of New Drugs and Product: ICH Q1 A (R2), 2003, 1- 20.
20. Cartensen JT and Rhodes CT., Drug stability: Principles and practices New York – Marcel Dekker; 3rd Edition, 329 – 384.
21. Riley CM and Rosanske TW., Progress in Pharmaceutical and Biomedical Analysis., Development and validation of analytical methods., 1st Edition ; Elsevier Science Ltd, USA, 1996, 133–135.
22. Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 94th Edition. CRC Press LLC, Boca Raton: FL 2013-2014, p. 3-314
23. Yalkowsky, S.H., He, Yan, Jain, P. Handbook of Aqueous Solubility Data Second Edition. CRC Press, Boca Raton, FL 2010, 492.
24. O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013, 10.
25. American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, 2212.
26. O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001, 876.
27. Yalkowsky SH, Dannenfelser RM; The AQUASOL database of Aqueous Solubility. Ver 5. Tucson, AZ: Univ AZ, College of Pharmacy, 1992.
28. Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980, 1057.
29. Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996, 712.
30. Testa, B. and P. Jenner. Drug Metabolism: Chemical & Biochemical Aspects. New York: Marcel Dekker, Inc., 1976, 22.
31. O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006, 522.
32. Finn A et al; Acta Technol Legis Med, 1986, 4: 33-44.
33. American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, 2113.
34. Anojo Hetal; Eur J Drug Metab Pharmacokinetic, 1999, 24(4): 345-51.
35. Hosale AV, Agrawal GP and Mishra P: Preparation and characterization of mutual Prodrugs of ibuprofen. IJPSR 2004; Vol. 2, Issue 4 ISSN: 0975-8232.
36. Koren, K., Mann, A.R., Colosimo, A.L., Diaz, Z., Nuclelman, A., Levovich, I., Jing, Y., Waxman, S. and Miller, W.H. Jr., Mol. Cancer Res., 2003, 1, 903.
37. Slemmer J.E., Martin B.R., Damaj M.I. Bupropion is a nicotinic antagonist. J. Pharm. Exp. Ther. 2000; 295: 321–327.
38. Wu C, Quan J, Xie J, Branford-White C, Zhu L, Yu Y, Wang Y. Preparation and controlled release of degradable polymeric ketoprofen-saccharide conjugates. Polym Bull. 2011; 67: 593–608.
39. Gennaro, R., Alfanso, W., Remington: The science and practice of pharmacy, Lippincott Williams & Wilkins, 2003, 20, 1, 913-914.
40. Shargel AB and Andrew BC, Applied Biopharmaceutics & Pharmacokinetics, 4th Ed. McGraw-Hill Medical Publishing Division, US. 47-66, 129-154.
Published
2017-08-01
How to Cite
[1]
Sen, D.J. 2017. Study of in-vitro biotransformation of prodrugs of Ester and Amide linkages of Ibuprofen, Diclofenac Sodium and Paracetamol in acidic and alkaline medium. PharmaTutor. 5, 8 (Aug. 2017), 49-65.
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