What is Preformulation
“Preformulation testing encompasses all studies enacted on a new drug compound in order to produce useful information for subsequent formulation of a stable and biopharmaceutically suitable drug dosage form” (Akers, M. J. Can. J. Pharm. Sci. 1976, 11, 1-10)
Why Do Preformulation Studies for Drug Selection?
It is useful to conduct preformulation studies and biopharmaceutics studies at the candidate drug selection stage to determine the most relevant physicochemical and biopharmaceutical properties of potential drugs to aid candidate selection.
The objective is to achieve a seamless transition from research to development, as opposed to the traditional “over-the-wall” approach that many pharmaceutical companies experience to their costs.
It begins in medicinal chemistry’s lead identification (polymorph only), lead optimization and prenomination (top 3 leads), followed by decision on API, salt, and polymorph.
The Route of Administration Dictates What’s Important
Ideally, for an oral solid dosage form, a water-soluble, nonhygroscopic, stable polymorph, and easily processed crystalline compound is preferred for development. For solid inhalation compounds, the API needs to be micronized or spay-dried. The micronization is an energy-intensive process and can change the crystallinity, may generate amorphous content and thus, their subsequent interaction with moisture (stability) may be important.
For a solution formulation, including inhalation products using nebulizers, the stability of the compound will be paramount. Compounds are less stable in solution than in solid-state.
Tests Important for a Rational Decision
From the MedChem stage there is already available data on the API: 1H/13C/2D-NMR, hi-resolution mass spec, elemental analysis, HPLC, IR/UV-vis, some solubility/stability information, hygroscopicity that needs to be shared with the development. The candidate selection process needs data on acidity constant(s) (pKa), partition and distribution coefficients (logP, logD), solubility, solution stability, and solid-state characterization: crystallinity, hygroscopicity, stability, and salt selection/early polymorph screening.
Clearview Pharma Solutions LLC (www.clearviewpharmallc.com), is a consulting company for drug development, offering two services: contract consulting and access retainer services. If this is something that interests you, I welcome a phone conversation at your convenience.