Active ingredient design/selection

Irritation. Tissue irritation upon injection, and the accompanying damage and pain, is a concern that must be addressed for the final formulation, which is to be either tested in humans or marketed, rather than for the active ingredient. This is because most irritation factors are either due to or influenced by aspects of formulation design (see Avis, 1985, for more information or parenteral preparations). These factors are not independent of the route (TV, IM, or SC) that will be used and, in fact (as discussed later), are part of the basis for selecting between the various routes. 

Step 4 Verification - here, the selected candidates are further analyzed in terms of their performance when they are applied for their designed use. Models capable of simulating their performance in their process of application are needed. These models may be process simulation models (for example, ICASSIM or ICAS-utility) as well as product application models (such as delivery of an active ingredient). 

A specified area of filter must be soaked in a specified volume of product for a designated time. The accelerated stability of active ingredients at 40-60°C for 60 days must be established prior to the selection of a filter for a particular purpose. The extent of damage, and the nature and quantity of extractables and their potency have to be evaluated. 

Expert systems for the design of the solvent mix should be further developed. In particular, proposals including the type of reaction working in a particular system should be included. The availability of larger and more reliable data sets would reduce the hurdles for applications. Especially for active pharmaceutical and agrochemical ingredient process developments, which have to be done within a short time frame. There is no time available to adapt new solvent systems. Therefore, sufficient data should be available to select a solvent mix within a few experiments. 

Controlled release of active materials is an important area of research. Controlled-delivery systems offer a number of potential advantages in many fields of applications. The design and the development of a new controlled-release system require a multidisciplinary approach. Polymer and material sciences play an important role. The selection of the formulation and the choice of the fabrication process are critical. In many cases, ingredients used in formulations should satisfy... 

In this chapter, the evolution of the active pharmaceutical ingredient (API) manufacturing process for sunitinib malate will be described. The different routes evaluated to prepare the API, the factors that influenced the choice of the commercial process, salt selection, scale-up experience, and regulatory issues will be discussed in detail. The benefits and challenges of developing a one-pot process will also be highlighted. It is hoped that this chapter will provide a sense of the spectrum of issues to be considered while designing a commercial process. 

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