During the last decades many different systems for modifying the release of an active drug substance from a pharmaceutical composition have been developed. Most of them aim at obtaining a zero or a first order release rate of the active substance from the composition. Zero order release rate (i.e. constant release of the active substance with time) seems to be very difficult to obtain from a pharmaceutical composition. The present invention is based on a polymeric matrix composition, which is construed to deliver the active substance in a zero order release manner. The present invention is a further development based on the Applicant's previously described drug delivery systems, see e.g. EP-B-0 406 315, EP-B-0 493 513, EP-B-0 740 310 and WO 99/51208 the disclosure of which is hereby incorporated by reference.
It is known to obtain a controlled release of an active substance e.g. by embedding it in a polyethylene glycol matrix, cf. WO 99/51208, EP-B-0 493 513 and EP-B-0 746 310 (to the same Applicant). However, one of the challenges that still need to be solved is to provide pharmaceutical compositions for e.g. slightly soluble drug substances, wherein the pharmaceutical composition after oral administration leads to an improved bioavailability compared to known compositions. Many crystalline, therapeutically active substances have a very slight solubility in aqueous medium such as, e.g., body fluids. It is well known that changing a crystalline compound into its amorphous state will substantially increase the aqueous solubility of the compound. Accordingly, during the last decades many attempts have been made to provide compositions having the active substance present in an amorphous form. However, the amorphous form is normally not a thermodynamically stable form and, accordingly, precipitation of the crystalline form may occur during storage. The present invention addresses the above-mentioned problems.
USPTO Backgrounds
USPTO Backgrounds