Oral Formulations of Kinase Inhibitors

Abstract

The present invention relates to formulations of bioactive compounds of limited water solubility, namely 2,4-diaminopyridine focal adhesion kinase (FAK) inhibitors, suitable for oral administration to patients. The formulation is self-emulsifying in the gastrointestinal tract of the patient, providing enhanced absorption and bioavailability of the bioactive compound in the form of a dispersion or emulsion in an oil base. For example, PEGylated glycerides can be used as the oil, in combination with surfactants such as lecithin and TEPG succinate and solubilizers such as polyethylene glycol 400, to contribute to adverse reactions in which inhibition of FAK is medically indicated. Useful orally administered pharmaceutical formulations are provided for patients with unhealthy conditions, such as cancer or arthritis.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 359,694, filed June 29, 2010, which is hereby incorporated by reference in its entirety. Background technique [0003] Small molecule inhibitors of various types of kinases have become important exploratory pharmaceutical compounds. However, certain kinase inhibitors are characterized by low water solubility and poor oral bioavailability. [0004] Among the various types of kinases, experimental small molecule inhibitors have been developed for a family known as focal adhesion kinases. Recently, focal adhesion kinase (FAK) has emerged as a key component in integrin-triggered signal transduction pathways. The aggregation of FAK with integrins and cytoskeletal proteins at focal adhesions has been proposed to be responsible for FAK activation. Recent results from a number of different approaches have demonstrated that integrins transduce signals...

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Problems solved by technology

However, some kinase inhibitors are characterized by low water solubility and poor oral bioavailability

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