Ibuprofen prodrugs

Daus, S. Heinze, T. (2010). Xylan-based nanoparticles Prodrugs for ibuprofen release. 

A comparison between carbamoylmethyl and aminoalkyl esters has been reported for a small series of prodrugs of ibuprofen (8.28) [39]. A further interest of this work is the systematic comparison made between the enantiomers of ibuprofen, i. e., the active (+)-(S)-form and the inactive (-)-(/ )-form. As shown in Table 8.4, the ethyl esters were hydrolyzed very slowly in human plasma, with t1/2 values in the order of 100 - 200 h. In contrast, the hydrolysis of the carbamoylmethyl and aminoalkyl esters occurred with t1/2 values in the order of some or several minutes. The carbamoylmethyl esters were hydrolyzed very rapidly with low substrate enantioselectivity, while the 2-(imidazol-l-yl)ethyl esters were hydrolyzed somewhat more slowly and with marked substrate enantioselectivity. 

Table 8.4. Prodrug Esters of the Enantiomers of Ibuprofen (8.28). Hydrolysis in 80% human...

Ibuprofen (8.28) and naproxen (8.26) were derivatized with the same l-[(ethoxycarbonyl)oxy] ethyl pro-moiety to yield two prodrugs designated as... 

N. Mprk, H. Bundgaard, Stereoselective Enzymatic Hydrolysis of Various Ester Prodrugs of Ibuprofen and Flurbiprofen in Human Plasma , Pharm. Res. 1992, 9, 492 - 496. 

E. Samara, D. Avnir, D. Ladkani, M. Bialer, Pharmacokinetic Analysis of Diethyl-carbonate Prodrugs of Ibuprofen and Naproxen , Biopharm. Drug Dispos. 1995, 16, 201-210. 

Shanbhag, V. R., Crider, A. M., Gokhale, R., et al. Ester and amide prodrugs of ibuprofen and naproxen Synthesis, anti-inflammatory activity, and gastrointestinal toxicity. J. Pharm. Sci. 81 149—154, 1992. 

Preparations from plant materials containing salicylate have been used to treat pain and fever (Stone, 1763) from ancient times into the nineteenth century, when synthetic salicylic acid was synthesized in Germany and used for the same purposes. Acetyl salicylate, aspirin, synthesized as a prodrug for salicylate, was introduced by Bayer in 1899 (Dreser, 1899) and is still widely used to treat pain, fever, and inflammation. In low doses aspirin is also used by many to reduce the incidence of heart attacks by an antithrombotic effect (Antiplatelet Trialists Collaboration, 1994). Eventually, other drugs with therapeutic effects similar to those of aspirin were introduced, including indomethacin, ibuprofen, and naproxen. These... 

Samara, E. Avoir, D. Ladkani, D. Bialer, M. Pharmacokinetic analysis of diethylcarbonate prodrugs of ibuprofen and naproxen. Biopharm.Drug Dispos., 1995, 16, 201-210... 

Previous papers have investigated the suitable use of xylan in papermaking [10] and textile printing [21]. In the drug delivery field, xylan extracted from birch wood has been used for the production of nanoparticles after structural modification by the addition of different ester moieties, namely those with furoate and pyroglutamate functions [21]. On the other hand, the esterification of xylan from beech wood via the activation of the carboxylic acid with iV,iV -carbonyldiimidazole has been carried out in order to produce prodrugs for ibuprofen release [10, 21, 22, 37]. 

Chen, J.C. and Tsai, S.W. (2000) Enantioselective synthesis of (S)-ibuprofen ester prodrug in cyclohexane by Candida rugosa lipase immobilized on... 

Figure 8.22 Prodrug esters of ibuprofen designed to reduce gastric irritation.

---