Bioavailability lipid formulations

Drug A is a large, peptide-like molecule (MW 700 g/mol) and is highly lipophilic and poorly water soluble. It is a BCS Class II drugs. Its oral bioavailability in capsules and conventional tablet formulations is low, yielding practically undetected blood levels. A novel lipid formulation containing a solvent, a high HLB nonionic surfactant, and a fatty acid were developed with sufLcient oral bioavailability for use in the clinic. 

Sek, L., et al., Examination of the impact of a range of pluronic surfactants nmvtfo solubilization behavior and oral bioavailability of lipidic formulations of atovaquodepharm. Pharmacql 58,... 

Likewise, several other studies have demonstrated that certain lipidic formulations can act as effective modulators of P-Gp counter transport systems, " " " which offers a qualitative explanation for enhanced drug transport in independently examined cases, for instance, increased bioavailability of cyclosporine when coadministered with water-soluble vitamin Thus, a... 

Griffin BT and O Driscoll CM (2006) A Comparison of Intestinal Lymphatic Transport and Systemic Bioavailability of Saquinavir from Three Lipid-Based Formulations in the Anaesthetised Rat Model. J Pharm Pharmacol 58 pp 917-925. 

Cuine, J. F., W N. Charman, C. W Pouton, G. A. Edwards, andC. J. H. Porter(2007). Increasingthe proportional content of surfactant (Cremophor EL) relative to lipid in self-emulsifying lipid-based formulations of Danazol reduces oral bioavailability in beagle ddgj3arm. Res., 24 748-757. 

FIGURE 11.1 Comparison of the bioavailability for four formulations of a lipophilic drug, RO-15-0778, in dogs. A Lipid-based SEDDS B PEG 400 solution C capsule (powder) D tablet. (AdaptedfromGershanik.T. and Benita, S. (200C ur. J. Pharm. Biopharm., 50 179-188.)... 

Use of these semisolid and solid approaches can potentially alleviate the chemical stability problems sometimes observed for liquid-Llled formulations, and may eventually offer the possibility of development of a tablet dosage form using conventional equipment. Liquid lipid-based formulations, however, generally afford the greatest enhancement of bioavailability for water-insoluble drugs, as well as affording more rapid development for First-in-Human studies. Any decisions on the best formulation route would have to be evaluated on a case-by-case basis. 

Khoo, S.-M. et al. (1998) Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrindnt. J. Pharm., 167 155-164. 

Vasanthavada, M. and A. T. M. Serajuddin. Lipid-based self-emulsifying solid dispersidripid-n Based Formulations for Oral Drug Delivery Enhancing the Bioavailability of Poorly Vteter-Soluble Drugs, ed. D. J. Flauss, 149-183. New York Informa Healthcare. 

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