HIGHLY STABLE COMPOSITIONS OF ORALLY ACTIVE NUCLEOTIDE ANALOGUES OR ORALLY ACTIVE NUCLEOTIDE ANALOGUE PRODRUGS

摘要

Disclosed are highly stable compositions having outstanding storage stability and/or demonstrating exceptional resistance to aqueous degradation, the composition including an orally active nucleotide analogue or an orally active nucleotide analogue prodrug, which is orally bioavailable, such as adefovir dipivoxil and tenofovir disoproxil. In particular molecular dispersions of adefovir dipivoxil in copovidone are disclosed. For example, when a composition of the invention is stored for 1 month or for 18 months at 25 ° C and 60% relative humidity, its orally active nucleotide analogue or orally active nucleotide analogue prodrug degrades to provide a composition containing no more than 0. 2% or no more than 0. 7% by weight of a less orally bioavailable impurity, respectively. Also disclosed are a container/closure package system including the composition and a package insert and methods of manufacturing the composition and treating a patient for a disease or condition, for example, a viral disease or cancer, with the use of the composition.