Oral modified release (MR) drug products remain highly prevalent in drug development pipelines. These dosage forms tailor the in vivo drug release profile to achieve improved therapeutic outcomes for drugs intended for both local (gastrointestinal) action and also systemic delivery. Patients with chronic and acute conditions benefit from the use of MR dosage forms given that they offer greater compliance and less frequent dosing regimens, coupled with potentially greater efficacy and fewer side effects in comparison to Immediate Release (IR) delivery systems.
A large number of MR technologies are available to drug developers, each designed to fulfill very specific performance requirements, such as gastro-retention or sustained-, pulsatile-, or delayed- release formats. The design and development of an effective MR formulation is however an inherently complex process, presenting many challenges for the development team. Human GI anatomy and physiology strongly influences drug release and performance of MR dosage forms given regional variations in pH, fluid volumes and compositions, surface area, metabolizing enzymes and membrane transporters. Challenges are exacerbated by an over-reliance on in vitro and preclinical test results to inform formulation prototype selection, despite evidence that these data often correlate poorly with pharmacokinetic performance in humans.
In this presentation we will discuss the drivers for MR development and key considerations for rational formulation design and technology selection. Using case studies, we will describe the specialized formulation technologies that are available in the “toolbox” in order to achieve an optimal target product profile, and the use of innovative, adaptive clinical programs where human PK data is used to optimize MR formulation compositions in real-time.
Key Discussion Topics:
- Bridging from an Immediate Release (IR) formulation to Modified Release (MR) - What drives the need and what are the benefits?
- Key formulation design strategies and technologies – Which approaches to deploy?
- The relationships between formulation parameters, in-vitro data and in-vivo performance – Can we establish an IVIVC?
- The use of Design Space concepts – How to evaluate and optimize formulation performance “real-time” using clinical data
- Featured Case Studies on Modified Release Drug Programs and MR Best Practices
Andrew Lewis, Vice President, Pharmaceutical Sciences, Quotient Sciences
