Issue link: https://www.e-digitaleditions.com/i/1138630
14 July 2019 Tablets & Capsules Companies develop OCR dosage forms for a number of reasons, including: • If an API is prone to degradation in acid, an OCR formulation will protect the API as it passes through the stomach. • If an API causes local irritation, an OCR formula- tion can spread it over a wider area, lowering the local concentration and minimizing the irritation. • If an API causes side effects at high plasma con- centrations, the lower C max can help prevent them from occurring (Figure 1). • If there is a lack of effect as the API's plasma con- centration drops below a certain threshold, an OCR product can help keep the plasma concen- tration within the desired range for longer, extending the duration of therapeutic effect. This allows less frequent dosing, making it easier for patients to stay on schedule and avoid periods of lack of effect (Figure 1). While these are the most common patient benefits of OCR dosage forms, not all benefits will be relevant to every product, and in some cases, these attributes are not beneficial. To determine the right mix of attributes to offer the best benefit profile for OCR products, carefully and holistically consider each API's pharmacokinetics, pharmacodynamics, side effects, therapeutic window, metabolism, absorption, and physicochemical behavior. In OCR product development, decisions made at the outset determine success. Selecting the final dosage form, developing the approach to formulation and processing, and avoiding common roadblocks are key. While a surpris- ingly wide variety of OCR formulations are possible, faulty planning for development and manufacturing can cost time and money and can potentially end a whole project. Diverse dosage forms offer a range of advantages and disadvantages for OCR medications. Tablets are faster, easier, and more economical to produce but limit the ability to fine-tune release profiles or dosages. Multiparticulate capsules allow for complex, timed deliv- Figure 1 Immediate versus sustained release profiles 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Plasma drug concentration Time (hours) Immediate release Sustained release Toxic Sub-therapeutic Maximum safe concentration Therapeutic window Minimum effective concentration Courtesy of Myke Scoggins, director, product development