Preformulation studies design

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. 

Mass transfer phenomena exist everywhere in nature and are important in the pharmaceutical sciences. We may think of drug synthesis preformulation studies dosage form design and manufacture and drug absorption, distribution, metabolism, and excretion. Mass transfer plays a significant role in each. Mass transfer is referred to as the movement of molecules caused not only by diffusion but also by convection [1],... 

Thermal methods have found extensive use in the past as part of a program of preformulation studies, since carefully planned work can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [2], It should be noted, however, that the use of differential scanning calorimetry (DSC) for such work is less in vogue than it used to be. Nevertheless, in appropriately designed applications, thermal methods of analysis can be used to evaluate compound purity,... 

Serajuddin, A.T.M., Sheen, P.C., Mufson, D., Bernstein, D.F., and Augustine, M.A., Preformulation study of a poorly water soluble drug, alpha-pentyl-3-(2-quinolinyl-methoxy) benzenemethanol selection of the base for dosage form design, /. Pharm. Sci., 75, 492, 1986. 

C. Ahlneck and J.O. Waltersson, Factorial designs in phamaceutical preformulation studies. II. Studies on dmg stability and eompatibility in the solid state. Act. Pharm. Suec., 23 (1986) 139. 

Serajuddin, A. T. M., P. C. Sheen, and M. A. Augustine. 1986. Preformulation study of a poorly water-soluble drugp<-pentyl-3-(2-quinolinylmethoxy) benzenemethanol Selection of base for dosage form design.J Pharm Sci75 492-496. 

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. 

From the summary data of the preformulation studies, scientists should obtain potential leads based on stability conditions designed in order to consider them for further development. The next stage of development, which we call formulation, should take into account all the parameters that may achieve one or more stable formulations for marketability with acceptable industrial stability. 

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. 

This guideline for conventional pharmaceuticals may be considered and incorporated into the stability section of preformulation study, when one designs a report for herbal drugs. 

A preformulation study is performed to gain insight from physicochemical and biological data into the design and development of dosage forms. Samples are taken in each study and analyzed qualitatively and/or quantitatively, according to the need. Therefore, proper selection of analytical techniques suitable for the purpose of each study is crucial to the success of the investigation. 

Waltersson JO. Factorial designs in pharmaceutical preformulation studies. Part 1. Evaluation of the application of factorial designs to a stability study of drugs in suspension form. Acta Pharm Suec 1986 23 129-138. 

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. 

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