Simple, immediate release (IR) and once-a-day (QD) formulations are desired not only by the patient for rapid onset and improved compliance, but also by the pharmaceutical industry due to ease of development and cost benefits. However, many small molecules in today’s pipelines have sub-optimal properties for QD IR formulations.
Challenges, including poor solubility or permeability, can lead to reduced absorption (input in the body) or high clearance (output from the body) that causes a short duration of therapeutic effect. This results in more frequent dosing regimens, which may not be suitable for patient compliance.
Another challenge comes from the significant peaks and troughs in circulating drug concentrations. Using IR formulations, the drug immediately enters the bloodstream, and if dosing is not optimized, this could lead to side effects for the patient and variation in therapeutic efficacy. For IR formulations that require more than once-a-day dosing, a modified release (MR) formulation, which delivers the drug to the lower GI tract over a sustained period, can be a better choice to achieve the desired therapeutic effects.
The following will discuss the opportunities and challenges when transitioning from an IR to MR formulation. It will review the therapeutic benefits and challenges associated with MR formulations, GI physiology environments and API physicochemical properties, technology choices, and how drug developers can achieve translation success.
To continue reading this article featuring Vanessa Zann, Executive Drug Development Consultant, visit the Drug Development & Delivery website.