Prodrugs pp 357-377 | Cite as

Controlled Release — Small Molecules

  • Jaymin C. Shah
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)


A prodrug is generally designed to improve the physical and chemical properties of a parent drug to enable formulation development, improve delivery, and/or achieve targeting. Similarly a prodrug approach can be used to enable development of a controlled release formulation, i.e., to provide a pharmacokinetic profile with sustained plasma levels. In the following discussion the term controlled release (CR) is used to include all prodrug approaches that result in sustained plasma levels over a dosing duration, thus reducing dosing frequency of the parent drug or the active moiety. CR technologies could include osmotic devices, polymeric matrix, implants, and microspheres and suspensions for parenteral depots that result in sustained plasma levels of the drug.


Ester Prodrug Haloperidol Decanoate Nandrolone Decanoate Fluphenazine Decanoate Prodrug Approach 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Al-Hindawi M, James K, and Nicholls P. The Influence of the Solvent on the Availability of Testosterone Propionate from Oily Injections. J Pharm Pharmacol 1981; 81:65PGoogle Scholar
  2. Al-Hindawi M, James K, and Nicholls P. The Influence of Solvent on the Availability of Testosterone Propionate from Oily Intramuscular Injections in the Rat. J Pharm Pharmacol 1987; 39:90–95PubMedGoogle Scholar
  3. Baker M, Gray B, Ohlsson-Wilhelm B, Carpenter D, and Muirhead K. Zyn-Linked Colchicines: Controlled-release Lipophilic Prodrugs with Enhanced Antitumor Efficacy. J Control Release 1996; 40:89–100CrossRefGoogle Scholar
  4. Cario Altamura, A, Sassella F, Santini A, Montresor C, Fumagalli S, and Mundo E. Intramuscular Preparations of Antipsychotics. Drugs 2003; 63:493–512PubMedCrossRefGoogle Scholar
  5. Chien YW, Long-Acting Parenteral Drug Formulations. J Parenter Sci Technol 1981; 35:106–139PubMedGoogle Scholar
  6. Cimbollek M, Nies B, Liebendorfer A, Wenz R, and Kreuter J. The Potential of the Prodrug Clindamycin Palmitate as an Implantable Slow Release form of the Antibiotic Clindamycin for Heart Valves. J Control Release 1995; 33:47–53CrossRefGoogle Scholar
  7. Drug Facts and Comparisons 2004, Facts and Comparisons, 58th Edition, 2003Google Scholar
  8. Gennaro AR. In: Remington: The Science and Practice of Pharmacy, Easton, PA: Mack Publishing Co., 19th Edition, 1995Google Scholar
  9. Hirabayashi H, Takahashi T, Fujisaki J, Masunaga T, Sato S, Hiroi J, Tokunaga Y, Kimura S, and Hata, T. Bone Specific Delivery and Sustained Release of Diclofenac, A Non-Steroidal Anti-inflammatory Drug via Bisphosphonic Prodrug Based on the Osteotropic Drug Delivery System (ODDS). J Control Release 2001; 70:183–191PubMedCrossRefGoogle Scholar
  10. Hirano K, Ichihashi T, and Yamada H. Studies on the Absorption of Practically Water-insoluble Drugs following Injection. I. Intramuscular Absorption from Water-immiscible Oil Solutions in Rats. Chem Pharm Bull 1981; 29:519–531PubMedGoogle Scholar
  11. Jolimaitre P, Malet-Martino M, and Martino R. Fluorouracil Prodrugs for the Treatment of Proliferative Vitreoretinopathy: Formulation in Silicone Oil and In Vitro Release of Fluorouracil. Int J Pharm, 2003; 259:181–192PubMedCrossRefGoogle Scholar
  12. Kawakami S, Nishida K, Mukai T, Yamamura K, Nakamura J, Sakaeda M, and Sasaki H. Controlled Release and Ocular Absorption of Tilisolol Utilizing Ophthalmic Insert-incorporated Lipophilic Prodrugs. J Control Release 2001; 76:255–263PubMedCrossRefGoogle Scholar
  13. Larsen S, Rinvar E, Sevndsen O, Lykkesfeldt J, Friis G, and Larsen C. Determination of the Disappearance Rate of Iodine-125 Labelled Oils from the Injection Site after Intramuscular and Subcutaneous Administration to Pigs. Int J Pharm 2001; 230:67–75PubMedCrossRefGoogle Scholar
  14. Luo J, Hubbard J, and Midha K. Studies on the Mechanism of Absorption of Depot Neuroleptics: Fluphenazine Decanoate in Sesame Oil. Pharm Res 1997; 14; 1079–1984PubMedCrossRefGoogle Scholar
  15. Luo J, Hubbard J, and Midha K. The Roles of Depot Injection Sites and Proximal Lymph Nodes in the Presystemic Absorption of Fluphenazine Decanoate and Fluphenazine: Ex Vivo Experiments in Rats. Pharm Res 1998; 15; 1485–1489PubMedCrossRefGoogle Scholar
  16. Minami K, Hirayama F, and Uekama K. Colon-Specific Drug Delivery Based on a Cyclodextrin Prodrug: Release Behavior of Biphenylacetic Acid from Its Cyclodextrin Conjugates in Rat Intestinal Tracts after Oral Administration. J Pharm Sci 1998; 87:715–720PubMedCrossRefGoogle Scholar
  17. Murdan S, and Florence A. Non-aqueous Solutions and Suspensions as Sustained-Release Injectable Formulations. In: Senior J, and Radomsky M. Sustained Release Injectable Products Denver, Co: Interpharm Press; 2000:71–108Google Scholar
  18. Nara E, Masegi M, Hatono T, and Hashida M. Pharmacokinetic Analysis of Drug Absorption from Muscle Based on a Physiological Diffusion Model: Effect of Molecular Size on Absorption. Pharm Res 1992; 9:161–169PubMedCrossRefGoogle Scholar
  19. Parfitt K, Martindale: The Complete Drug Reference, London, UK: Pharmaceutical Press, 32nd Edition, 1999Google Scholar
  20. Physicians’ Desk Reference®-2004. Thomson Healthcare, The Medical Economics Company. 58th Edition, 2004.Google Scholar
  21. Radd B, Newman A, Fegely B, Chrzanowski F, Lichten L, and Walking W. Development of Haloperidol in Oil Injection Formulations. J Parenter Sci Technol 1985; 39:48–50PubMedGoogle Scholar
  22. Sandborn W. Rational Selection of Oral 5-Aminosalicylate Formulations and Prodrugs for the Treatment of Ulcerative Colitis. Am J Gastroenterol 2002; 97:2939–2941PubMedCrossRefGoogle Scholar
  23. Senior J. Insoluble Salt Forms and Drug Complexes. In: Senior J, and Radomsky M. Sustained Release Injectable Products. Denver, Co: Interpharm Press; 2000:41–70Google Scholar
  24. Song Y, Onishi H, Machida Y, and Nagai T. Drug Release and Antitumor Characteristics of N-succinyl-chitosa-mitomycin C as an Implant. J Control Release 1996; 42:93–100CrossRefGoogle Scholar
  25. Steffansen B, Ashton P, and Buur A. Intraocular Drug Delivery, In Vitro Release Studies of 5-Fluorouracil from N1-alkoxycarbonyl Prodrugs in Silicone Oil. Int J Pharm 1996; 132:243–250CrossRefGoogle Scholar
  26. Sung K, Han R, Hu O, and Hsu L. Controlled Release of Nalbuphine Prodrugs from Biodegradable Polymeric Matrices: Influence of Prodrug Hydrophilicity and Polymer Composition. Int J Pharm 1998; 172:17–25CrossRefGoogle Scholar
  27. Tanaka T, Kobayashi H, Okumura K, Muranishi S, and Sezaki H. Intramuscular Absorption of Drugs from Oily Solutions in the Rat. Chem Pharm Bull 1974; 22:1275–1284PubMedGoogle Scholar
  28. Tipton A, and Dunn R. In Situ Gelling Systems. In: Senior J, and Radomsky M. Sustained Release Injectable Products. Denver, Co: Interpharm Press; 2000:241–278Google Scholar
  29. Woolfson A, Elliott G, Gilligan C, and Passmore C. Design of an Intravaginal Ring for the Controlled Delivery of 17-β-Estradiol as its 3-acetate Ester. J Control Release 1999; 61:319–328PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Jaymin C. Shah
    • 1
  1. 1.Pfizer Global Research & DevelopmentPharmaceutical R & DGroton

Personalised recommendations