In addressing problems of bioavailability and solubility, "there are two dimensions to which to address solubility of poorly
soluble drugs, the drug substance and drug product," says Kurt Nielsen, PhD and senior vice-president, innovation and growth
with Catalent Pharma Solutions, in commenting on the survey results. With respect to the drug substance, he points to various
solutions, such as optimizing the salt form or solid-state form (i.e., polymorph or co-crystal). Slight modifications to the
drug substance also can be made to improve solubility, such as converting the drug to a prodrug, or by reducing the particle
size of the drug substance, explains Nielsen.
With respect to the drug product, Nielsen says that various methods can improve solubility, ranging from straightforward strategies,
such as solubilizing agents (e.g., surfactants and polymers) to more complex solutions where site-specific drug release is
required to address such issues as poor stability of the drug in the stomach or pre-systematic metabolism in certain locations
in the gastrointestinal tract. As with the drug substance, particle engineering can be used to not only optimize solubility
but also to modify or control the release of the drug, he adds. In sum, these strategies seek to address the key aspects of
solubility, permeability, and site of absorption.
On a dosage form level, various approaches may be used. "Liquid-based dosage forms, such as softgels, dispersion-based dosage
forms through hot-melt or spray-dried dispersions, and drug layering and coating can be used to improve solubility and bioavailability
of oral dosage forms," says Nielsen. If bioavailability is still a problem, other routes of administration, such as transdermal,
buccal, and sublingual drug delivery can be considered.
1. Catalent–Pharmaceutical Technology Landscape Drug Delivery Survey (December 2011).