Dosage forms preformulation

A drug substance must be chemically and physically characterized prior to incorporation into a new dosage form. Preformulation work provides the type of information needed to define the nature of the drug substance, as thoroughly as possible, and this then provides the framework for the drug s combination with pharmaceutic ingredients in the fabrication of a dosage form. 

It should again be emphasized that at the onset of a new drug program, there are only small amounts of drug substance at hand. One of the first tasks for the preformulation scientist is to establish the framework within which the first clinical batches can be formulated. To this end it is important to know with which common excipients the drug is compatible. Below, the distinction will be made between solid and liquid dosage forms. 

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],... 

One approach to the study of solubility is to evaluate the time dependence of the solubilization process, such as is conducted in the dissolution testing of dosage forms [70], In this work, the amount of drug substance that becomes dissolved per unit time under standard conditions is followed. Within the accepted model for pharmaceutical dissolution, the rate-limiting step is the transport of solute away from the interfacial layer at the dissolving solid into the bulk solution. To measure the intrinsic dissolution rate of a drug, the compound is normally compressed into a special die to a condition of zero porosity. The system is immersed into the solvent reservoir, and the concentration monitored as a function of time. Use of this procedure yields a dissolution rate parameter that is intrinsic to the compound under study and that is considered an important parameter in the preformulation process. A critical evaluation of the intrinsic dissolution methodology and interpretation is available [71]. 

Gibson, M., Pharmaceutical Preformulation and Formulation A Practical Guide from Candidate Selection to Commercial Dosage Form, CRC Press LLC, Leicestershire, 2004. 

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. 

Broadhead, J., Parenteral dosage forms, in Pharmaceutical Preformulation and Formulation, Gibson, M., Ed., Interpharm/CRC Press, New York, 2004. 

Motola, S. andAgharkar, S.N. Preformulation research of parenteral medicaticRteatmaceutical Dosage Forms Parenteral Medications, Vol.2t d ed., Edited by K.E. Avis, H.A. Lieberman, and L. Lachman, Marcel Dekker, New York, NY, 1992, pp. 158-163, Chapter 4. 

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. 

As part of the preformulation activities, investigations include physiochemical character, purity, solubility, stability, and optimal pH studies. In preparation for clinical studies, potential product formulations considering route of administration and solution stability are also studied. Unique to dosage form development studies for lyophilized products, thermal analysis of the drug substance and product formulations are also necessary. Data generated during this phase of product development is useful for future development activities, along with validation. 

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. 

Nyqvist H, Wadsten T. Preformulation of solid dosage forms light stability testing of polymorphs as a part of a preformulation process. Acta Pharm Technol 1986 32 130-132. 

Preformulation in Solid Dosage Form Development, edited by Moji Christianah Adeyeye and Harry G. Brittain... 

Davies P. 2004. Oral solid dosage form. In Gibson M, editor. Pharmaceutical preformulation and formulation. Interpharm/CRC New York 379-456. 

Gibson, M. (2001), Pharmaceutical preformulation and formulation a practical guide from candidate drug selection to commercial dosage form, IHS Health Group, Englewood, Colorado. 

ROLE OF PREFORMULATION IN DEVELOPMENT OF SOLID DOSAGE FORMS... 

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