title: Amorphous Solid Dispersions or Prodrugs: Complementary Strategies to Increase Drug Absorption.
abstract: Maximizing oral bioavailability of drug candidates represents a challenge in the pharmaceutical industry. In recent years, there has been an increase in the use of amorphous solid dispersions (ASDs) to address this issue, where a growing number of solid dispersion formulations have been introduced to the market. However, an increase in solubility or dissolution rate through ASD does not always result in sufficient improvement of oral absorption because solubility limitations may still exist at high doses. Chemical modification in the form of a prodrug may offer an alternative approach for these cases. Although prodrugs have been primarily used to improve membrane permeability, examples are available in which prodrugs have been used to increase drug solubility beyond what can be achieved via formulation approaches. In this mini review, the role of ASDs and prodrugs as 2 complementary approaches in improving oral bioavailability of drug candidates is discussed. We discuss the fundamental principles of absorption and bioavailability, and review available literature on both solid dispersions and prodrugs, providing a summary of their use and examples of successful applications, and cover some of the biopharmaceutics evaluation aspects for these approaches.
authors.affiliation: Formulation Sciences, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033. Electronic address: alfred.rumondor@merck.com.
authors.forename: Alfred C F
authors.initials: ACF
authors.lastname: Rumondor
authors.affiliation: Formulation Sciences, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033; Technical Research and Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936.
authors.forename: Sundeep S
authors.initials: SS
authors.lastname: Dhareshwar
authors.affiliation: Biopharmaceutics, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors.forename: Filippos
authors.initials: F
authors.lastname: Kesisoglou
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006801:Humans; D065568:Oral Mucosal Absorption; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011355:Prodrugs
keywords: absorption; amorphous; bioavailability; oral drug delivery; prodrugs; solubility