Aggregate with increased deformability, comprising at least three amphipats, for improved transport through semi-permeable barriers and for the non-invasive drug application in vivo, especially throug

Abstract

The application describes combinations of at least three amphipatic substances forming aggregate suspensions in a polar liquid. Judicious choice of system components, which differ at least 2-times to 10-times in solubility, ensures said aggregates to have extended, unusually adaptable surfaces. This is probably due to simultaneous action on said aggregates of at least two more soluble substances amongst said three system components, at least one of which is an active ingredient and preferably a drug; the third component, alternatively, can take the role of a drug. The application further deals with the use of said combinations in pharmaceutical preparations capable of transporting drugs into the body of warm blood creatures. This is made possible by the drug loading capability of said aggregates with the highly flexible and deformable coating, which renders the resulting drug carriers highly adaptable. The application finally reveals suitable methods and favourable conditions for carrier manufacturing and application. The application also describes novel formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) based on complex aggregates with at least three amphipatic components suspended in a suitable, e.g. pharmaceutically acceptable, polar liquid medium.

Description

Technical field [0001] The present application relates to aggregates (extended surface aggregates (extended surface aggregates, ESA)) with expanded surfaces, which have enhanced deformability and improved barrier penetration capabilities. The ESA can be suspended in A suitable liquid medium contains at least three amphipathic components (amphipat) (amphipatic components) and can improve the transport of the active substance through a semipermeable barrier such as the skin, specifically This aggregate is allowed to penetrate the barrier to apply non-invasive drugs to the body. These three amphiphilic substances include at least one membrane forming compound (MFC) that forms the film of the ESA, and at least two membrane destabilizing (membraned estabilising) compounds (MDC). 1 And MDC 2 ), the film destabilizing compounds differ in their ability to form small aggregates (without spreading surface) when alone or in combination with each other and / or are characterized by relatively h...

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Problems solved by technology

However, the results of the study showed that the application of lipid vesicles is not beneficial (Calpena et al., 1999)

[0026] A study of the skin permeability data for ibuprofen showed that in practice the drug penetration rate was equivalent in solution or in mixed micelles (containing soybean phosphatidylcholine), but in the corresponding lipid dispersion The penetration rate in is almost three times lower (Stoye et al., 1998 (Eur J Pharm Biopharm 46:191-200)

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