Preformulation Studies: A Foundation for Dosage Form Development

The development of an efficient dosage form is usually a long and complex process that involves a lot of capital and teamwork from different disciplines. Prior to dosage form development, it is absolutely necessary that certain fundamental properties of candidate drug molecules are determined. This helps the formulator to generate useful information that could prevent the successful and productive development of an efficient dosage form. This exploratory stage of drug development during which the physicochemical properties of drug molecules are characterized either alone or in combination with excipients is known as preformulation.
Preformulation studies are carried out on candidate drug molecules that show sufficient pharmacological promise in animal model. The information obtained may dictate many subsequent events and approaches in dosage form development. This blog post will highlight the objectives, goals and classes of preformulation, as well as what to consider before starting a preformulation study and finally evaluated parameters in preformulation studies.

Objectives of preformulation studies

1. To generate useful data needed in developing stable and safe dosage forms that can be manufactured on a commercial scale.
2. To provide in-depth knowledge and understanding of the physical characteristics of a candidate drug molecule prior to dosage form development.
3. To generate useful information on how to design a drug delivery system with good bioavailability.

Goals of preformulation studies

1. To establish the physicochemical parameters of a candidate drug molecule.
2. To determine the kinetic rate profile of drug substances.
3. To establish the compatibility of a candidate drug molecule with common excipients.

Classes of preformulation studies

Preformulation studies can be classified into:

a. Fundamental preformulation studies

These studies are specific to candidate drug molecules and it include solubility analysis (e.g., ionization constant, partition coefficient, solubilization, thermal effect, common ion effect, dissolution etc.), solid state properties (e.g., polymorphism, solvated forms and amorphous form ), stability analysis (e.g., solution-state stability and solid-state stability) and permeability studies. These studies are dependent on the chemical structure of the candidate drug molecule.

b. Derived preformulation studies

These studies include characterization of particle properties (e.g., particle size and particle shape), bulk density, powder flow properties, compaction behaviour etc. They are carried out on the intended dosage form.

What to consider before starting a preformulation study

Before embarking on preformulation studies, scientists must consider

1. The available physicochemical data including chemical structure, different salts, potency relative to the competitive products and the dosage form etc.
2. Anticipated dose and the proposed route of drug administration.
3. Supply situation and development schedule.
4. Availability indicating assay.

Evaluated parameters in preformulation studies

a. Physical characteristics

1. Organoleptic properties of the candidate drug molecule e.g., colour, odour and taste.
2. Bulk characterization e.g., particle size and surface area, powder flow properties, density, compressibility, crystallinity, polymorphism and hygroscopicity.
3. Solubility analysis e.g., ionization constant/ drug Pka, partition coefficient, solubilization, thermal effect, common ion effect (Ksp) and dissolution.
4. Stability analysis e.g., solution-state stability testing, solid-state stability testing, and drug-excipient compatibility studies.

b. Chemical characteristics

1. Hydrolysis
2. Oxidation
3. Photostability
4. Racemization
5. Polymerization
6. Isomerization

These parameters will be discussed in the subsequent posts.
References

• Leo, A., Hansch C., and Elkins D. (1971). Partition Coefficients and Their Uses. Chemical Reviews, 71(6): 525-616.
• Kumar, P., Vaishnavi, G., Divya, K. and Lakshmi, U. (2015). An Overview on Preformulation Studies. Indo American Journal of Pharmaceutical Science, 2(10): 1399-1407.
• Chaurasia G. (2016). A Review on Pharmaceutical Preformulation Studies in Formulation and Development of New Drug Molecules. International Journal of Pharmaceutical Science and research, 7(6): 2313-2320.
• Kulkarni, S., Sharma, S. and Agrawal, A. (2015). Preformulation – A Foundation For Formulation Development. International Journal of Pharmaceutical, Chemical And Biological Sciences, 5(2): 403-406.
• Gibson, M. (2004). Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Commercial Dosage Form. Florida: CRC Press LLC.
• Onyishi, I. V. (2015). Lecture on Personal Collection of Onyishi, University of Nigeria, Nsukka, Enugu State.

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