Stability studies formulation development

Figure 10.10 Stability studies analysis by LC-MS. Long-term stability studies (3 months, 30°C) are evaluated by LC-MS analysis of a C-terminal peptide fragment. Various degradation mechanisms are visualized, removal of C-terminal residues due to proteolytic activities, isomerization and deamidation of specific asparagine residues. Future development efforts will allow the use of this methodology to assess progress toward a stable formulation.

Drug development work also includes formulation, stability studies, and selection of drug delivery systems, as discussed in Section 5.6. Once the API has been prepared, excipients are added ... 

The level 3 method is used until synthetic routes and formulations have been finalized and forced degradation and preliminary stability studies have been conducted i.e., until the components that need to be separated in the final DS and in the final DP have been clearly determined. At this juncture, the focus shifts to the development of fast, robust and transferable final methods to be used for primary stability studies and post-approval analyses. Freqnently, separate methods are developed for DS and DP since the goals of each method are different (see Section I). Orthogonal methods continue to be of importance to troubleshoot any questions that may arise during the subsequent life cycle of the drug. 

The physiochemically and biologically characterized proteins and peptides are further formulated and subject to stability studies. The goal of these studies is to develop a unique combination of excipients, solution pH, buffer, and container that will produce an optimum dosage form. Biopharmaceutical formulations should be... 

Formulation Development. The formulation is finalized based on the experience gained in the manufacture of clinical phase I and II trial materials. Scale-up of the manufacturing process will be completed to qualify the manufacturing capability of the facility. The primary stability study is initiated to assess the stability of the drug product. 

The formulation development strategies are similarto thatifoivo PK screening. It is common to use supersaturated solutions in the early phase studies. However, the physical and chemical stabilities of the supersaturation systems should be well understood as the information provided will help formulation scientists to decide if the formulation needs to be prepared daily, weekly or monthly. 

El-Banna HM, Ismail AA, Gadalla MAF. Factorial design of experiment for stability studies in the development of a tablet formulation. Pharmazie 1984 39 163-165. 

Stability studies during the IND phase provide not only assurance of the quality of clinical trial material but also the basis for the drug product development program. Stability data are used to evaluate different formulations, methods of manufacture, and container-closure systems, as well as to determine storage requirements, expiration dating periods, and specifications. 

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