Low colonic absorption drugs: risks and opportunities in the development of oral extended release products

ABSTRACT

Introduction: Currently numerous drugs have been observed with lower colonic absorption than small intestine absorption, which can significantly impact in vivo performance of their oral extended release (ER) products.

Areas covered: We reviewed over 300 publications, patents, book chapters, and commercial reports of drug products from regulatory agencies for low colonic absorption (LCA) drugs and critical findings are discussed. The focuses of this article are (1) current findings on the causes of low colonic absorption to support early assessment of LCA candidates, and (2) current knowledge on successful ER strategies and technical platforms used for LCA drugs in commercial drug products to facilitate oral ER product development.

Expert opinion: Colonic drug absorption is one of the critical considerations in successful development of oral ER products. The root causes of low colonic absorption in many LCA drugs are still unclear. It is recommended to evaluate colonic drug absorption of drug candidate at early stage of oral ER product development. After evaluation, the selection of a formulation platform to develop an oral ER product needs to be carefully considered for LCA drugs. Based on the current commercial oral ER formulation platforms for LCA drugs, compounds are first divided into five types (I-V) and different ER formulation approaches with higher success rate are recommended for each type.

KEYWORDS:

• Extended release
• colonic absorption
• regional absorption
• formulation
• prodrug
• product development

Article highlights

• Currently numerous drugs have been observed with lower colonic absorption than small intestine absorption, which can significantly impact in vivo performance of their oral extended release (ER) products.

• To date, only a few publications disclosed the causes of low colonic absorption (LCA) and the root causes of many LCA drugs are still unclear. In this review, potential factors which may cause regional absorption difference are discussed.

• The identification of LCA compound currently relies on the in vivo evaluation. Therefore, a general instruction for early assessment of LCA candidates is proposed and related practical concerns are discussed.

• The successful strategies and technical platforms applied to commercial products for LCA drugs are reviewed and discussed. Other technologies which have shown promising clinical results for LCA compounds are also covered.

• Based on the elimination half-life and F_colon, compounds are first divided into five types (I-V) and different ER formulation approaches with higher success rate are recommended for each type.

This box summarizes key points contained in the article.

Declaration of interest

J Xu, Y, Lin, P Boulas and M. L. Peterson are employees of Biogen Inc - Pharmaceutical Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

No funding was received for this paper.