ABSTRACT
Poor solubility is a major obstacle in the development of drug formulations. In many cases the poor solubility is associated with poor bioavailability. In addition, low-solubility drugs possess a low dissolution velocity. The challenge is to circumvent this problem by designing sophisti cated delivery systems. Basically, drugs can be poorly soluble in:
1. Water and aqueous media, 2. Aqueous and (simultaneously) organic media
In the case of drugs being poorly soluble in aqueous media, a range of formulation ap proaches are available (1) such as the use of solubilizing solutions, complexing agents such as cyclodextrins, and mixtures of water with organic media (e.g., water-ethanol, water-propylene glycol). However, for many drugs these approaches do not lead to a sufficiently high increase in solubility, dissolution velocity, and subsequent bioavailability. Especially for drugs that are simultaneously poorly soluble in water and organic media, these approaches are of limited success (e.g., solubiliz ing solutions) or cannot be used at all (e.g., mixture of water and organic media). The traditional for mulation for such drugs is micronization by a jet mill or using wet milling. Micronization leads to an increase in surface area and subsequently, according to the Noyes-Whitney equation, to an in crease in the dissolution velocity. However, micronization is only an efficient tool in case the disso lution velocity is the rate-limiting factor for absorption, i.e., the factor limiting the bioavailability. It does not work in case the poor saturation solubility itself is the rate-limiting factor.
