Fig. 2.26. Formulation Issues in Drug Administration
Active pharmaceutical ingredients need to meet specifications (e.g., purity, potency, physical/chemical/biological properties). For injections, we need to consider the solution's pH, ionic strength, solvents, buffers, stabilizers, and preservatives. Special formulations will have their own unique considerations, for example, inhalation (particle size), topical (skin penetration), and ophthalmic (mix with tears).
A product is not one single entity that is discovered, studied, and marketed at one point in time. A life cycle exists for all products, wherein it evolves in its uses, properties, and formulation over time (Fig. 2.27). A company attempts to get the most scientific benefits from its investment in a product for patient care improvements and, of course, maximum financial gain. However, to fully capitalize on the product, a life cycle plan (LCP) must be created as early as possible to literally map out the full potential of a product and the resources that it might take to achieve all the opportunities. The LCP is a dynamic document; as more data becomes available over time, you iterate the LCP. You can suggest more than 10 different stages in a life cycle; that is, discovery of molecule, preclinical product, product in clinical trials (first indication), approved and marketed for one indication (hopefully novel, first to market), added countries for marketing, product with competition, added indications, expanded labeling for added dosing schema, unexpected adverse experience limiting use, new formulations, follow-on molecules in the family or by in-licensing, off-patent with generic substitution, and over-the-counter product. Many of these stages will require added product development and costs regarding clinical trials to create the data and file an abbreviated NDA to obtain labeling changes. New formulation work may require clinical trials to establish efficacy, but at least new manufacturing, pharmacokinetic, and stability work will be necessary. Sustained-release formulations are often developed later in the product's life cycle once the initial efficacy is established with the simpler first-generation form. Then, enhanced convenience (e.g. once daily vs. four times a day dosing) becomes an important focus. The LCP needs early development to plan, schedule, and integrate milestones, timelines, work requirements, cost projections, market research, and revenue impacts. For example, Enbrel® was approved first for rheumatoid arthritis, with later indications established for juvenile arthritis, psoriatic arthritis, psoriasis, and ankylosing spondilytis, as well as follow-on molecules and other dosing schema being evaluated. The statin anticholesterol drugs were over-the-counter products in Europe by 2004. Pegylation was done for interferons and filgrastim to slow their clearance from the body and improve their clinical utility with less frequent dosing and also extending their patent protection [51, 52].
Was this article helpful?
Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.