Product design preformulation studies

Process validation is intended to show and document that the process described, when operating within the designated parameters, will produce product of the appropriate quality and demonstrate that the manufacturing process is under full control. Process validation should extend from laboratory-scale and preformulation studies (say to of production scale) to formulation to pilot-scale manufacture (say production scale) to full industrial-scale manufacture, with a clear, logical, and continuous path between these stages. The magnitude of scale-up at each stage should not normally exceed a factor of 10. 

Preformulation testing of the specific API of interest and key excipients to be used in the product design stage, alone and in combinations with the API, should be included as a preliminary first step in the product and process development sequence. A simple check list of items worth consideration in preformulation studies with APIs and important or critical excipients is provided as follows ... 

Following successful preformulation studies, the API is transferred to the formulations laboratory for preliminary product design and development studies. In most cases, the drug is mixed with an appropriate diluent or... 

Preformulations From an industrial point of view, preformulation studies are designed to cover a wide range of properties in a short time and to learn as much as possible, but not in great depth. The studies should focus on the identification of potential problems early enough to evaluate potential alternatives to stabilize future formulations that could lead to a product. 

In the preformulation study, the comprehension of physicochemical properties regarding water-solid surface interaction is beneficial to the handling, formulation, and manufacture of the finished products. Data on sorption/de-sorption isotherm, hydration of salts of drug product, water sorption of pharmaceutical excipients, and kinetics of water adsorption or desorption of a substance can be obtained effectively by the dynamic vapor sorption method. The knowledge may be utilized for dosage form design and supports the understanding of the mechanism of action. 

Obviously, not all conditions are met, but by every compound we keep this direction in mind, it is easier to sift through many possibilities offered. It requires testing a range of selected compounds in in vitro and in vivo animal studies and thus, preformulation work gets combined with biopharmaceutic studies to identify product design issues. 

Preformulation is usually defined as the science of the physicochemical characterization of candidate drugs. However, any studies carried out to define the conditions under which the candidate drug should be formulated can also be termed preformulation. This is a broader definition than was used in Chapter 3, and, as such, it can include studies on preliminary formulations under a variety of conditions. These studies may influence the Product Design and should be conducted at the earliest opportunity at the start of development. In the interest of faster drug development and reduced drug usage, preformulation studies should not be undertaken on a check-list basis. Rather, they should be conducted on a need-to-know basis. 

The exact product optimisation studies to be conducted will depend on the type of ophthalmic dosage form to be developed (liquid drops, semi-solid gel/ointment or solid device). However, the dosage form type should be clearly defined from the product design evaluation and supporting preformulation studies, to enable the formulator to focus on the most relevant product optimisation studies. 

Physicochemical properties of proteins, peptides, and monoclonal antibodies must be identified in order to develop preformulation and formulation studies with rational designs. Specific stabilizers play a major role in stabilizing the product under specific experimental conditions. 

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