Bioavailability enhancement

P-CD was also reported to improve the biodegradation of a single hydrocarbon (dodecane) (15). y-CD, HPBCD, and RAMEB were effective in the intensihcation of PCB biodegradation in soils (10, 16). Especially remarkable bioavailability-enhancing properties were exhibited by RAMEB in hydrocarbon-polluted soils (17). Because soil bioremediation needs months to years depending on type and concentration of the contaminants, soil properties, and microflora, an additive that degrades slowly in the soil is required. RAMEB meets this requirement. Its half-life time is about 1 year in a soil contaminated with motor oil (18), while HPBCD is decomposed rapidly (19). (Adapted from Jozefaciuk et ah, 2003)... 

Constituent of oral and topical pharmaceuticals Bioavailability enhancer and solubilizer... 

PYA copolymer Bioavailability enhancer Single-dose toxicity (in rat and dog) and maximum tolerated dose/short-term (2wks—oral) (in rat and dog) toxicity as well as 2 in vitro and 1 in vivo genotoxicity studies. ADME studies with 14C-labelled material are underway and a 3-6 mo toxicity study in the rat is planned No adverse effects seen to date 41... 

It is generally believed that the mechanism of bioavailability enhancement by CD complexation is through solubility and dissolution rate improvement. However, it should be also noted that CDs might also alter the lipid barrier of the absorption site, which may contribute to the enhanced drug absorption. This effect of CDs on the lipid barrier can be attributed to CDs ability to form complexes with membrane components such as cholesterol, phospholipids, and proteins (Nakanishi et al., 1992). Jambhekar et al. (2004) compared the solubilizing effeqte D, HP-ft-CD, and H -CD on IM. 

Basavaraj, S., Sihorkar, V., Kumar, T. R. S., Sundaramurthi, P., Srinivas, N. R., Venkatesh, P., Ramesh, M., and Singh, S. K. 2006. Bioavailability enhancement of poor water soluble and weakly acidic new chemical entity with 2-hydroxy propyl -cyclodextrin selection of meglumine, a polyhydroxy base, as a novel ternary componenPharm. Dev. TechH 443—451. 

Joshi, H. N., R. W. Tejwani, M. Davidovich, V. P. Sahasrabudhe, M. Jemal, M. S. Bathala, S. A. Varia, and A. T. M. Serajuddin. 2004. Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol-polysorbate 80 mixtdnfc. J. Pharm. 269 251-258. 

Porter, C.J. and Charman, W.N., Lipid-based formulations for oral administration opportunities for bioavailability enhancement and lipoprotein targetingfor lipophilic drilc ecept. Signal Transduct. 

Varma, M.V., et al. 2003. P-glycoprotein inhibitors and their screening A perspective from bioavailability enhancement. Pharmacol Res 48 347. 

The ability of lipid vehicles (either in the pharmaceutical formulation or in food) to enhance the absorption of lipophilic drugs has been well known for many years. Recently, successful bioavailability enhancement utilizing lipid-based formulations has been accomplished with the immunosuppressive agent cyclosporine A (Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ), and for the two HIV protease inhibitors ritonavir (Norvir, Abbott Laboratories, IL) and saquinavir (Fortovase, Roche Pharmaceuticals, Nutley, NJ). Consequently, considerable interest in lipid-based formulations has been aroused. 

Opportunities for Bioavailability Enhancement and Lipoprotein Targeting of Lipophilic Drugs... 

In this chapter we will provide a brief overview of the early approaches to bioavailability enhancement by use of simple lipid-based delivery systems (lipid solutions, emulsions etc), and then describe recent progress in the application of self-emulsifying- and microemulsion-based formulations. The effects of lipids on the oral bioavailability of co-administered poorly water-soluble drugs may also be classified from a mechanistic (and to a degree, historical) perspective as physicochemically mediated effects (solubility, dissolution, surface area) and biochemically mediated effects (metabolism, transport related events), and these will be approached separately. It is readily apparent, however, that in many cases physicochemically and biochemically mediated mechanisms will operate side by side. In some instances, bioavailability may also be enhanced by the stimulation of intestinal lymphatic transport, and these studies will be addressed in a separate section. 

B. Bioavailability Enhancement by Means of Biochemical/Metabolic Mechanisms... 

In contrast, data from a recent conference presentation by Choc and Robinson [100], indicated that cyclosporin metabolite ratios were similar after oral administration of either Sandimmun or the Neoral formulation, suggesting minimal changes in cyclosporin first-pass metabolism after Neoral administration. Furthermore, Neoral/Sandimmun area under the curve (AUC) ratios were similar (approximately 2) after cyclosporin administration in either the absence or presence of a CYP3A/P-gp inhibitor, whereas an AUC ratio of approximately 1 would have been expected if bioavailability was limited by metabolism or antitransport. However, these data have not yet been published, and the relative contributions of enhanced absorption or reduced metabolism in the CY bioavailability enhancement provided by Sandimmun Neoral are yet to be fully defined. 

Piperine (1-piperoyl piperidine) is shown to possess bioavailability-enhancing activity with various structurally and therapeutically diverse drugs. Piperine s bioavailabil-ity-enhancing property may be attributed to... 

Although all the active targeting liposomes mentioned earlier have not left the laboratory, nonspecific sterically stabilized liposomes are being tested in clinical trials. Doxorubicin is the anticancer agent which is used as standard therapy, and it has the most serious side effects (mucositis, cardiotoxicity), so its incorporation in liposomes and bioavailability enhancement are under scrutiny [386-388]. 

Yun M, Choi H, Jung J, Kim C. Development of a thermo-reversible insulin liquid suppository with bioavailability enhancement. Int J Pharm 1999 189(2) 137-145. 

Kang BK, Lee JS, Chon SK, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm 2004 274 65-73. 

Yin SX, Franchini M, Chen J, etui. Bioavailability enhancement of a COX-2 inhibitor. BMS-347070, from a nanocrystalline dispersion prepared by spray-drying. J niaim Sci 2005 94 1598-607. 

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