Luigi Martini

Controlling Drug Release in Oral Product Development Programs: An Industrial Perspective

Most new drugs for oral administration are released rapidly from the dosage form. This may give “peak-trough” plasma profiles not suited to the drug’s mode of action or side effect profile. Traditionally, there were few options for better design to optimize rate or time of release. However, advances in many areas of drug evaluation are now identifying opportunities to modify drug release during earlier phases of development to optimize therapeutic efficacy and reduce undesirable effects. It should also result in better success rates in drug development programs as well as better medications for patient treatment. This chapter explores possibilities for modifying release during Preclinical, Phase 1, Phase 2, and Phase 3 programs. Opportunities to improve performance or find new indications for mature drugs, by controlling release continue to emerge. Such possibilities are also considered. The chapter is written, not only for the product design (formulation) specialist but also for scientists involved in all aspects of drug evaluation and development. Consequently, its focus is on the breadth rather than depth of the topic. Other chapters provide more comprehensive accounts of specific approaches, technologies, and modes of evaluation.

Novel Manufacturing Technologies for the Production of Patient-Centric Drug Products

The dose forms that the pharmaceutical industry provides to elderly patients are far from ideal in many regards, and recent trends in the industry have emphasized the potential benefits that may be obtained by emphasizing the patient’s needs in the formulation and manufacturing design process (as noted by Van Riet-Nales et al. [1], Stegemann et al. [2]), i.e., “age-related formulations.” Naturally, the physical and chemical properties of the active pharmaceutical ingredient (or “API”) constrain the set of viable potential dose forms, and biological factors, which have a significant influence on oral drug absorption in a wide range of patient groups, are critical aspects of formulation and manufacturing process selection. The development of an oral drug product that can be manufactured using a robust process is a critical element both of providing a suitable medicine of appropriate quality to the patient and a commercial return to the pharmaceutical company. Within this highly constrained design problem, it may be possible for the industry to develop new approaches by thinking creatively about the entire set of highly connected formulation and manufacturing challenges, and to remodel factory operations or, potentially, whole supply chains. Regulators, and the pharmaceutical companies themselves, have historically taken a conservative approach to novel manufacturing technologies that may offer quality and cost advantages over the conventional supply chain paradigms. Innovations, in the examples discussed below, will not be adopted rapidly, as change on such a scale occurs slowly. However, it is interesting to consider the benefits that such drug product manufacturing innovations might provide to patients. In recent years, regulators and the industry have sought to develop such approaches that not only offer patient benefits but that do so at commercially acceptable costs, and which are designed using robust and established manufacturing engineering principles.