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Poor aqueous solubility of a drug can lead to issues during the preclinical phase of drug development and beyond. Insufficient solubility within the gastrointestinal lumen can limit absorption and subsequent exposure to the drug in question. Thus, the solubility of a drug candidate will impact upon decisions and risk assessments undertaken during development.

There has been an increase in the proportion of poorly water‐soluble drugs with estimates of up to 75% of candidates in development being classified as low aqueous solubility [2]. This trend towards increasing proportions of low aqueous solubility drugs is linked to the drive towards potent and selective drugs where candidate optimisation often adds lipophilic groups to enhance binding, yet the lipophilicity of the resulting molecule increases. However, poorly water‐soluble candidate drugs are associated with higher rates of attrition as well as higher costs during drug development [3]. Furthermore, poorly water‐soluble drugs are associated with greater inter‐individual pharmacokinetic variability as well as being susceptible to food effects [3].

Solubility data will determine the need for an enabling formulations (e.g., wetting agents, micronisation, solubilising agents, solid solutions, emulsions and nanoparticles).

The importance of solubility is recognised within the biopharmaceutics classification system, where further details are provided in Chapter 9.