Dosage preformulation studies

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],... 

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. 

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. 

In order to develop a robust formula for a drug product (pharmaceutical dosage form) it is important to understand the chemical and physical properties of the API in conjunction with excipients that may be used to create the most stable product formula in terms of activity and potency. An outline of possible preformulation studies that should be conducted to ensure a proper and complete understanding of the chemical and physical properties of the API is presented in Table 3. 

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. 

Heidemann, D.R. Jarosz, P.J. Preformulation studies involving moisture uptake in solid dosage forms. Pharm. Res. 1991, 8, 292-297. 

The focus of this chapter is a discussion of various preformulation studies related to tablet dosage form development. The physicochemical properties of interest can be divided into two broad categories (r) molecular properties which are intrinsic to the drug substance and cannot be modified without chemical modification of the API. and ii) physical properties, which are amenable to modification to suit the needs of formulation. The molecular and the physical properties are listed in Table 1. 

To establish quality assurance, control of dosage forms, starting from clinical trial to production for market introduction, must be imposed on in-process operations and product testing for compliance with the specifications and guidelines of quality operation to ensure product attributes. Occasionally, specifications may be revised because of new evidence discovered in the continuous preformulation study. 

The first step in the product development process is establishing specifications after exploratory research to bring a product to market. Specifications are the quality definition of an article (dosage forms or the related materials for production) upon which acceptance for eventual market distribution is based. The data for establishing pharmaceutical product specifications for both drug substances and dosage forms are defined by identity, purity, strength, and quality, derived from the preformulation study. 

The contents and definition of preformulation studies included are generally broader than those found in published articles or conventional textbooks. The intent is to include articles to assist the formulator in developing an optimal and ideal dosage form either for marketing or for subsequent reformulation. Thus, the following considerations should be included in a comprehensive preformulation report. 

For liquid dosage forms of water-insoluble drugs, solubilization is an important tool in preformulation studies for the selection of surfactants. When... 

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. 

In a preformulation study, the intent of initiating the stability evaluation is to define a stability detection system that identifies potential degradation products and includes analytical methods for their quantitation. Subsequently, this system is utilized to monitor the degradation process of a new drug either by itself or in a dosage form for a specific period of time, such as the product shelf life. 

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. 

FdPLC has contributed many successes in product development and in quality control for the pharmaceutical industry. The UV detector coupling with HPLC equipment is the most important analytical instrument for preformulation, QC/QA, and in-process control in pharmaceutical analysis. HPLC is a basic and reliable analytical tool for preformulation study because of the high-resolution capacity, accuracy, and reproducibility of the equipment. Its primary function includes search for and detection of impurities in drug substances, as well as stability evaluation of dosage forms in terms of detection and quantitation of degradation products. 

Preformulation studies inevitably extend beyond the basic characterization of the lead compound, because what is considered as an acceptable characteristic of a lead compotmd will largely depend on the intended or anticipated dosage form. For example, the solubility issues will largely determine the route of administration conversely, if a particular route of administration is the only desired route, then preformulation studies should attempt to find out the structural changes necessary for the candidate molecule. 

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