Final product formulations stabilizing excipients

In addition to the studies listed in Figure 4.5, stability characteristics of the protein with regard to e.g. temperature, pH and incubation with various potential excipients are studied. Such information is required in order to identify a suitable final product formulation, and to give an early indication of the likely useful shelf-life of the product (Chapter 6). 

Stabilizing excipients used in final product formulations... 

No matter what delivery form is chosen, the components of the carrier should be evaluated for their compatibility with the final product formulation in which they will be incorporated. Likewise is tiue for their safety profiles. Moreover, components that are already approved globally should be considered, especially if the product is to be used worldwide. It is possible that certain components may be more suitable for particular applications, but higher concentrations of certain excipients may not be desirable. Having chosen a desired delivery system, all enzyme formulations should be evaluated for their shelf stability as stand-alone products. Stability evaluations should encompass activity and phase stability after several freeze/thaw cycles, at elevated temperatures and in humid environments, and long-term stability at ambient and cold temperatures. 

Great effort should be taken to stabilize a formulation in such a way that the shelf life becomes independent of the storage conditions. The photostability of drugs and excipients should be evaluated at the formulation development stage in order to assess the effects of packaging on the stability of the final product. Molsidomine tablet preparations in inadequate primary containers (blister) without secondary containers when exposed to irradiation may produce morpholine. These results illustrate the importance of packaging for the stability of molsidomine [19]. 

With the results of the preformulation studies, the formulation scientist can begin to address some of the specific questions pertaining to the development of the final formulation. The state of the dosage form is selected. The inactive ingredients in the formulation, excipients, which promote stability of the final product, are screened. Finally, supportive accelerated stability studies are conducted to aid in the selection of the final formulation. 

It is stated that nasal sprays have unique characteristics with respect to formulation, container closure system, manufacturing, in-process and final controls and stability. The product must deliver reproducible doses during the whole life of the product. Excipient controls are discussed in the FDA draft guidance in many respects, the chemistry, manufacturing and controls (CMC) standards expected of excipients are starting to approach those required of the active pharmaceutical ingredient (API). 

The following four examples are presented to illustrate the importance of understanding the properties of excipients and their stability. These examples have been encountered in the author s laboratories. They represent likely concerns in many company s future stability studies where these common excipients are used in their formulations. The information can be important to the quality of the pharmaceutical products in which they are used. This information aids in the selection of the right excipient for the product and helps in evaluation of the stability data for the final product. 

Finally, knowledge of excipient mechanical and physical properties is essential to creating a robust formulation that manufactures tablets that meet specifications in a time- and material-efficient manner. Excipient selection must also take into consideration API stability and biopharmaceutical performance of the dosage form. Uneducated selection of excipients will likely lead to numerous formulating iterations that require much time and material, which are luxuries that product development scientists do not have in the competitive pharmaceutical environment. 

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