Preformulation is the link between the drug discovery and drug delivery. When a important molecule is discovered by drug discovery department its important for the drug development people to work with the molecule to make it as suitable stable drug substance. Preformulation is playing a significant role in characterization of the molecule along with compatible nature of the molecule with different excipients to make this important molecule as suitable dosage form.
Goals of preformulation
- To choose correct correct form of drug substance
- To evaluate its physical and chemical properties
- To generate a thorough understanding of material stability under the conditions that will lead to development of practical drug delivery system
Criteria for preformulation
Physicochemical characterization of solid and solution properties of compounds - data useful for formulation of drug into suitable delivery system.
The developed formulation should have acceptable limit of bioavailability profile - solubility and absorption of molecule should be extracted from preformulation studies
Preformulation of solid dosage forms
There are many dosage forms are existing in the drug development still the solid dosage forms (eg. Tablets and capsules) are important due to its advantages. So, the focus of this pages is related to preformulation aspects involved in tablet formulation. Historically, the preformulation stage of drug development has been considered to consist mostly of drug substance profiling, and indeed most of the leading reviews have followed this view (1-6). Preformulation would also extend to studies of drug-excipient compatibilities.
Preformulation is nothing more than the API profiling along with excipient compatibility studies. There is a hostorical way of preformulation is trying all the combination of excipients with the drug substance and ruleout the possible combination for desired formulation. Recently the High-through put screening for developing the physical and chemical properties of drug substance and excipient.
Most preformulation is start during the lead optimization (LO) phase, even sometimes it start at lead identification stage to ruleout some undesirable features, like chirality, polymorphism, hygroscopicity, and stability problems. Preformulation should adress the fine balance between pharmacology, toxicology, and biopharmaceutical combatibility and bringing out an optimally available oral durg.
Characterization approaches in drug discovery and preformulation
- Nuclear Magnetic Resonance (NMR)
- Mass Spectra
- Elemental Analysis
- Karl Fischer
- pKa, Log P/log D
- Initial Solubility
- Crystal Structure
- Stability in solution and HPLC
- Other spectroscopical datas.
Salt forms : Dynamic Vapor Sorption (DVS), X-ray, Differential Scanning Calorimetry (DSC) / Differential Thermal Analysis (DTA) / Hot stage microscopy (HSM), Scanning Electron Microscopies (SEM), stability testing using temperature and humitidy.
There are many techniques and methods are adopted by drug discovery and drug delivery department, and preformulation is link between these two ends of drug development. The existence of agreement between drug discovery and preformulation with various characterization methodologies will bring out a best drug delivery system.
1. Fiese EF, Hagen TA. Preformulation (chap. 8). In: Lachman L, Lieberman HA, Kanig JL, eds. Theory and Practice of Industrial Pharmacy. Philadelphia: Lea & Febiger, 1986, pp. 171-96.
2. Wells JI, Aulton ME. Preformulation (chap. 13). In: Aulton ME, ed. Pharmaceutics: The Science of Dosage Form Design. Edinburgh: Churchill Livingstone, 1988, pp. 223-53.
3. Wadke DA, Serajuddin ATM, Jacobson H. Preformulation testing (chap. 1). In: Lieberman HA, Lachman L, Schwartz JB, eds. Pharmaceutical Dosage Forms, 2nd ed., vol. 1. New York: Marcel Dekker, 1989, pp. 1-73.
4. Carstensen JT. Preformulation (chap. 9). In: Carstensen JT, Rhodes CT, eds. Drug Stability, 3rd ed. New York: Marcel Dekker, 2000, pp. 237-60.
5. Carstensen JT. Preformulation (chap. 7). In: Banker GS, Rhodes CT, eds. Modern Pharmaceutics, 4th ed. New York: Marcel Dekker, 2002, pp. 167-85.
6. Ando HY, Radebaugh GW. Property-based drug design and preformulation (chap. 38). In: Hendrickson R, ed. Remington: The Science and Practice of Pharmacy, 21st edn. Philadelphia: Lippincott Williams & Wilkins, 2005, pp. 720-44.