Role of Prodrugs in Solubility Enhancement of Drugs
Keywords:
Prodrugs, Solubility Enhancement of Drugs, dissolution rate, bioavailability
Abstract
Solubility is one of the essential parameters to achieve bioavailability of drug in systemic circulation to produce expected therapeutic response. Nearly 40% of new drug molecules face solubility challenge. Though several techniques like micronization, crystal engineering, hydrotrophy, solid dispersion and so forth were available for solubility enhancement of poorly soluble drugs based on physical and chemical modification, prodrug approach is a vital technique amongst the other. Prodrugs are biologically inactive compound which can be metabolized in the body to produce active drug. It is estimated that currently about 10% of all world-wide approved drugs are prodrugs. This review extensively confers the role of prodrugs and the kind of promoieties used for solubility enhancement.
References
1. Sharma D., Soni M., Kumar S., and Gupta G.D; Solubility enhancement- eminent role in poorly soluble drugs; Research Journal of Pharmacy and Technology; 2009; 2(2); 220–224
2. Kristiina Huttunen M., Hannu Raunio., and Jarkko Rautio; Prodrugs-from Serendipity to Rational Design; Pharmacol Rev; 2011; 63(3); 750-771
3. Higuchi T., Stella V., Pro-drugs: An overview and definition, ACS Symposium Series, Washington DC, Ame. Chem. Soc; 1975; 1-115
4. Albert A; Chemical aspects of selective toxicity, Nature; 1958; 182; 421-422
5. Li X; Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications
6. Bentley R; Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence beta-lactams). J. Ind. Microbiol Biotechnol; 2009; 36; 775–786
7. Harper N.J; Drug Latentiation; Journal of Medicinal Chemistry; 1959; 1; 467-500
8. Harper N J; Drug Latentiation; Prog. Drug Res; 1962; 4; 221–294
9. Stella V.J., Charman W.N., and Naringrekar V.H; Prodrugs. Do they have advantages in clinical practice Drugs; 1985; 29; 455-473
10. Sinkula A., Yalkowsky S.H., Rationale for design of biologically reversible drug derivatives: Prodrugs; J. Pharm. Sci; 1975; 2; 181-200
11. Higuchi T., and Stella V; Prodrugs as Novel Drug Delivery Systems; American Chemical Society; Washington, DC; 1975
12. Roche E.B. Design of Biopharmaceutical Properties through Prodrugs and Analogs; American Chemical Society; Washington, DC; 1997.
13. Timmins G.S., and Deretic V; Mechanisms of action of isoniazid; Mol. Microbiol. 2006; 62; 1220–1227
14. Sawynok J; The therapeutic use of heroin: a review of the pharmacological literature; Can. J. Physiol. Pharmacol; 64; 1–6
15. Rautio J., Hanna Kumpulainen., and Tycho Heimbach; Prodrug: design and clinical applications, Nature; 2008; 7; 255-268
16. Inturrisi C.E., Schultz M., Shin S., Umans J.G., Angel L., and Simon E.J; Evidence from opiate binding studies that heroin acts through its metabolites; Life Sciences; 1983; 33; 773–776
17. Rautio J; Prodrug strategies in drug design, in Prodrugs and Targeted Delivery: Towards Better ADME Properties (Rautio J ed) pp 1–30, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; 2010
18. Stella V.J; Prodrugs Strategies for Improving Drug Like Properties: In Optimizing the Drug-Like Properties of Leads in Drug Discovery; Springer; New York; 2006; 221-242
19. Stella V.J; Drugs; 1985; 29; 455
20. Stella V.J., Burchardt R.T., Hageman M.J., Oliyai R., Maah H., and Tilley J.W; Prodrugs: Challenges and Rewards; Springer; New York; 2007; 1
21. Harle U.N., Gaikwad N.J; Principle and Industrial application of Pharmacokinetics and Biopharmaceutics; Nirali Prakashan; Pune; 2008; 15.1-15.18
22. Smith., and Williams; Introduction to the Principles of Drug Design and Action; Taylor and Francis Group, USA; 4; 216-230
23. Stella V.J., Burchardt R.T., Hageman M.J., Oliyai R., Maah H., and Tilley J.W; Prodrugs: Challenges and Rewards; Springer, New York; 2007; 1
24. Stella V.J; Prodrugs as therapeutics; Exp. Opin. Ther. Patents; 2004; 14; 277-280
25. Stella V.J; Prodrugs Strategies for Improving Drug Like Properties: In Optimizing the “Drug-Like” Properties of Leads in Drug Discovery; Springer, New York; 2006; 221-242
26. Stella VJ et al; Drugs; 1985; 29; 455
27. Kalgutkar A.S., Marnett A.B., Crews B.C., Remel R.P., Marnet L.J; J. Med. Chem; 2000; 43(15); 2860-2870
28. Singh G., Wadhwa L.K., Sharma S; J. Sci. Ind. Res; 1996; 55; 497-510
29. Bhosale D., Bharambe S., Gairula N., and Dhaneshwar S.S; Ind. J. Pharm. Sci; 2006; 68(3); 286-294
30. Kopecek J., and Duncan R; Targetable Polymeric Prodrugs; J. Contr. Rel; 2003; 6; 315–337
31. Fleisher D; Improved oral drug delivery solubility limitations overcome by the use of prodrugs; Adv. Drug Delivery Rev; 1996; 115
32. Wise R; After pro-drugs-mutual pro-drugs; J. Antimicrob. Chemother; 1981; 7, 503-504
33. Bhosle D., Bharambe S., Gairola N., and Dhaneshwar S.S; Mutual prodrug concept: Fundamentals and applications; Indian Journal of Pharmaceutical Sciences; 2006; 68; 286-294
34. Stella V.J; Prodrugs: Challenges and Rewards Part 1 and 2; Springer Science Business Media, Newyork; 2007
35. Stella V.J; Prodrug Strategies to overcome poor water solubility; Adv. Drug. Deliv. Rev; 2007; 59; 677-694
36. Sauer R., Maurinsh J., Reith U., Fulle F., Klotz K.N., and Muller C.E; Water-soluble phosphate prodrugs of 1-propargyl-8-styrylxanthine derivatives, A2a-selective adenosine receptor antagonists; J. Med. Chem; 2000; 43; 440-448
37. Mc Comb., Bowers G.N., and Posen S; Alkaline Phosphatases; Plenum Press; New York; 1979; 986-987
38. Stella V.J., and Nti-Addae K.W; Prodrug strategies to overcome poor water solubility; Adv. Drug. Deliv. Rev; 2007; 59; 677-694
39. Sauer R., Maurinsh J., Reith U., Fulle F., Klotz K.N., Muller C.E; Water-soluble phosphate prodrugs of 1-propargyl-8-styrylxanthine derivatives, A2a-selective adenosine receptor antagonists; J. Med. Chem; 2000; 43; 440-448
40. Safadi M., Oliyai R., Stella V.J; Phosphoryloxymethyl carbamates and carbonates-novel water-soluble prodrugs for amines and hindered alcohols; Pharm. Res; 1993; 10; 1350-1355
41. Kristiina M., Huttunen., and Jarkko Rautio; Prodrugs - An Efficient Way to Breach Delivery and Targeting Barriers; Current Topics in Medicinal Chemistry; Bentham Science Publishers; 2011
42. Schmidt F; Prodrug mono Therapy: synthesis and biological evaluation of an Etoposide glucuronide prodrug; Bio. org. Med. Chem; 2003; 11; 2277-2283
43. Kwon Y; Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug metabolism for Industrial Scientists; Kluwer Academic Publishers: Hingham; 2002
44. Yang C.Y; Intestinal peptide transport systems and oral drug availability; Pharm. Res; 1999; 16; 1331-1343
45. William D.B., Varia S.A., and Stella V.J; Evalution of the prodrug potential of the sulfate esters of acetaminophen and 3-hydroxymethyl-phenytoin; Int. J. Pharm; 1983; 14; 113-120
46. Miyabo S., Nakamura T., and Kuwazima S; A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man; Eur. J. Clin. Pharmacol; 1981; 20; 277-282
47. Sohma Y., Hayashi Y; Development of water-soluble prodrugs of the HIV-1 protease inhibitor KNI-727; J. Med. Chem; 2003; 46(19); 4124-4135
48. Almansa C., Bartroli J., Belloc J., Cavalcanti F.L., Ferrando R., and Gomez L.A; New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective inhibitor cimicoxib. A novel approach to sulfonamide prodrugs; J. Med. Chem; 2004; 47; 5579-5582
49. Greenwald R.B., Choe Y.H., Mc Guire J; Tripartate poly (ethylene glycol) prodrugs of the open lactone form of camptothecin; Bio org. Med. Chem; 2003; 11; 2635-2639
50. Nielsen L.S., Slok F., and Bundgaard H; N-alkoxycarbonyl prodrugs of mebendazole with increased water solubility; Int. J. Pharm; 1994; 102; 231-239.
2. Kristiina Huttunen M., Hannu Raunio., and Jarkko Rautio; Prodrugs-from Serendipity to Rational Design; Pharmacol Rev; 2011; 63(3); 750-771
3. Higuchi T., Stella V., Pro-drugs: An overview and definition, ACS Symposium Series, Washington DC, Ame. Chem. Soc; 1975; 1-115
4. Albert A; Chemical aspects of selective toxicity, Nature; 1958; 182; 421-422
5. Li X; Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications
6. Bentley R; Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence beta-lactams). J. Ind. Microbiol Biotechnol; 2009; 36; 775–786
7. Harper N.J; Drug Latentiation; Journal of Medicinal Chemistry; 1959; 1; 467-500
8. Harper N J; Drug Latentiation; Prog. Drug Res; 1962; 4; 221–294
9. Stella V.J., Charman W.N., and Naringrekar V.H; Prodrugs. Do they have advantages in clinical practice Drugs; 1985; 29; 455-473
10. Sinkula A., Yalkowsky S.H., Rationale for design of biologically reversible drug derivatives: Prodrugs; J. Pharm. Sci; 1975; 2; 181-200
11. Higuchi T., and Stella V; Prodrugs as Novel Drug Delivery Systems; American Chemical Society; Washington, DC; 1975
12. Roche E.B. Design of Biopharmaceutical Properties through Prodrugs and Analogs; American Chemical Society; Washington, DC; 1997.
13. Timmins G.S., and Deretic V; Mechanisms of action of isoniazid; Mol. Microbiol. 2006; 62; 1220–1227
14. Sawynok J; The therapeutic use of heroin: a review of the pharmacological literature; Can. J. Physiol. Pharmacol; 64; 1–6
15. Rautio J., Hanna Kumpulainen., and Tycho Heimbach; Prodrug: design and clinical applications, Nature; 2008; 7; 255-268
16. Inturrisi C.E., Schultz M., Shin S., Umans J.G., Angel L., and Simon E.J; Evidence from opiate binding studies that heroin acts through its metabolites; Life Sciences; 1983; 33; 773–776
17. Rautio J; Prodrug strategies in drug design, in Prodrugs and Targeted Delivery: Towards Better ADME Properties (Rautio J ed) pp 1–30, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; 2010
18. Stella V.J; Prodrugs Strategies for Improving Drug Like Properties: In Optimizing the Drug-Like Properties of Leads in Drug Discovery; Springer; New York; 2006; 221-242
19. Stella V.J; Drugs; 1985; 29; 455
20. Stella V.J., Burchardt R.T., Hageman M.J., Oliyai R., Maah H., and Tilley J.W; Prodrugs: Challenges and Rewards; Springer; New York; 2007; 1
21. Harle U.N., Gaikwad N.J; Principle and Industrial application of Pharmacokinetics and Biopharmaceutics; Nirali Prakashan; Pune; 2008; 15.1-15.18
22. Smith., and Williams; Introduction to the Principles of Drug Design and Action; Taylor and Francis Group, USA; 4; 216-230
23. Stella V.J., Burchardt R.T., Hageman M.J., Oliyai R., Maah H., and Tilley J.W; Prodrugs: Challenges and Rewards; Springer, New York; 2007; 1
24. Stella V.J; Prodrugs as therapeutics; Exp. Opin. Ther. Patents; 2004; 14; 277-280
25. Stella V.J; Prodrugs Strategies for Improving Drug Like Properties: In Optimizing the “Drug-Like” Properties of Leads in Drug Discovery; Springer, New York; 2006; 221-242
26. Stella VJ et al; Drugs; 1985; 29; 455
27. Kalgutkar A.S., Marnett A.B., Crews B.C., Remel R.P., Marnet L.J; J. Med. Chem; 2000; 43(15); 2860-2870
28. Singh G., Wadhwa L.K., Sharma S; J. Sci. Ind. Res; 1996; 55; 497-510
29. Bhosale D., Bharambe S., Gairula N., and Dhaneshwar S.S; Ind. J. Pharm. Sci; 2006; 68(3); 286-294
30. Kopecek J., and Duncan R; Targetable Polymeric Prodrugs; J. Contr. Rel; 2003; 6; 315–337
31. Fleisher D; Improved oral drug delivery solubility limitations overcome by the use of prodrugs; Adv. Drug Delivery Rev; 1996; 115
32. Wise R; After pro-drugs-mutual pro-drugs; J. Antimicrob. Chemother; 1981; 7, 503-504
33. Bhosle D., Bharambe S., Gairola N., and Dhaneshwar S.S; Mutual prodrug concept: Fundamentals and applications; Indian Journal of Pharmaceutical Sciences; 2006; 68; 286-294
34. Stella V.J; Prodrugs: Challenges and Rewards Part 1 and 2; Springer Science Business Media, Newyork; 2007
35. Stella V.J; Prodrug Strategies to overcome poor water solubility; Adv. Drug. Deliv. Rev; 2007; 59; 677-694
36. Sauer R., Maurinsh J., Reith U., Fulle F., Klotz K.N., and Muller C.E; Water-soluble phosphate prodrugs of 1-propargyl-8-styrylxanthine derivatives, A2a-selective adenosine receptor antagonists; J. Med. Chem; 2000; 43; 440-448
37. Mc Comb., Bowers G.N., and Posen S; Alkaline Phosphatases; Plenum Press; New York; 1979; 986-987
38. Stella V.J., and Nti-Addae K.W; Prodrug strategies to overcome poor water solubility; Adv. Drug. Deliv. Rev; 2007; 59; 677-694
39. Sauer R., Maurinsh J., Reith U., Fulle F., Klotz K.N., Muller C.E; Water-soluble phosphate prodrugs of 1-propargyl-8-styrylxanthine derivatives, A2a-selective adenosine receptor antagonists; J. Med. Chem; 2000; 43; 440-448
40. Safadi M., Oliyai R., Stella V.J; Phosphoryloxymethyl carbamates and carbonates-novel water-soluble prodrugs for amines and hindered alcohols; Pharm. Res; 1993; 10; 1350-1355
41. Kristiina M., Huttunen., and Jarkko Rautio; Prodrugs - An Efficient Way to Breach Delivery and Targeting Barriers; Current Topics in Medicinal Chemistry; Bentham Science Publishers; 2011
42. Schmidt F; Prodrug mono Therapy: synthesis and biological evaluation of an Etoposide glucuronide prodrug; Bio. org. Med. Chem; 2003; 11; 2277-2283
43. Kwon Y; Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug metabolism for Industrial Scientists; Kluwer Academic Publishers: Hingham; 2002
44. Yang C.Y; Intestinal peptide transport systems and oral drug availability; Pharm. Res; 1999; 16; 1331-1343
45. William D.B., Varia S.A., and Stella V.J; Evalution of the prodrug potential of the sulfate esters of acetaminophen and 3-hydroxymethyl-phenytoin; Int. J. Pharm; 1983; 14; 113-120
46. Miyabo S., Nakamura T., and Kuwazima S; A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man; Eur. J. Clin. Pharmacol; 1981; 20; 277-282
47. Sohma Y., Hayashi Y; Development of water-soluble prodrugs of the HIV-1 protease inhibitor KNI-727; J. Med. Chem; 2003; 46(19); 4124-4135
48. Almansa C., Bartroli J., Belloc J., Cavalcanti F.L., Ferrando R., and Gomez L.A; New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective inhibitor cimicoxib. A novel approach to sulfonamide prodrugs; J. Med. Chem; 2004; 47; 5579-5582
49. Greenwald R.B., Choe Y.H., Mc Guire J; Tripartate poly (ethylene glycol) prodrugs of the open lactone form of camptothecin; Bio org. Med. Chem; 2003; 11; 2635-2639
50. Nielsen L.S., Slok F., and Bundgaard H; N-alkoxycarbonyl prodrugs of mebendazole with increased water solubility; Int. J. Pharm; 1994; 102; 231-239.
Published
2014-12-01
How to Cite
[1]
G, K., S, V., A, V., Ch, N. and B, S. 2014. Role of Prodrugs in Solubility Enhancement of Drugs. PharmaTutor. 2, 12 (Dec. 2014), 33-48.
Section
Articles
