Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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; 81:65P
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; 39:90–95
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; 40:89–100
Cario Altamura, A, Sassella F, Santini A, Montresor C, Fumagalli S, and Mundo E. Intramuscular Preparations of Antipsychotics. Drugs 2003; 63:493–512
Chien YW, Long-Acting Parenteral Drug Formulations. J Parenter Sci Technol 1981; 35:106–139
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; 33:47–53
Drug Facts and Comparisons 2004, Facts and Comparisons, 58th Edition, 2003
Gennaro AR. In: Remington: The Science and Practice of Pharmacy, Easton, PA: Mack Publishing Co., 19th Edition, 1995
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; 70:183–191
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; 29:519–531
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; 259:181–192
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; 76:255–263
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; 230:67–75
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; 1079–1984
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; 1485–1489
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; 87:715–720
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; 2000:71–108
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; 9:161–169
Parfitt K, Martindale: The Complete Drug Reference, London, UK: Pharmaceutical Press, 32nd Edition, 1999
Physicians’ Desk Reference®-2004. Thomson Healthcare, The Medical Economics Company. 58th Edition, 2004.
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; 39:48–50
Sandborn W. Rational Selection of Oral 5-Aminosalicylate Formulations and Prodrugs for the Treatment of Ulcerative Colitis. Am J Gastroenterol 2002; 97:2939–2941
Senior J. Insoluble Salt Forms and Drug Complexes. In: Senior J, and Radomsky M. Sustained Release Injectable Products. Denver, Co: Interpharm Press; 2000:41–70
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; 42:93–100
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; 132:243–250
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; 172:17–25
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; 22:1275–1284
Tipton A, and Dunn R. In Situ Gelling Systems. In: Senior J, and Radomsky M. Sustained Release Injectable Products. Denver, Co: Interpharm Press; 2000:241–278
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; 61:319–328
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 American Association of Pharmaceutical Scientists
About this chapter
Cite this chapter
Shah, J.C. (2007). Controlled Release — Small Molecules. In: Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., Tilley, J.W. (eds) Prodrugs. Biotechnology: Pharmaceutical Aspects, vol V. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49785-3_9
Download citation
DOI: https://doi.org/10.1007/978-0-387-49785-3_9
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-49782-2
Online ISBN: 978-0-387-49785-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)