DRUG FORMULATION

Pharmaceutically active molecules are rarely administered as a pure chemical but combined with various excipients into a formulation that is designed to ensure that the active ingredient is delivered in a safe, effective, and reproducible manner as possible. Solid dosage forms for oral administration are the most common formulations, but formulations may also be liquid or semi-solid depending on the routes of administration and therapeutic indications.

Excipients, although considered to be essentially chemically inert, have specific functionality within a formulation. Constituents added to a formulation that has no specific functionality are considered to be adulterants. For solid dosage forms, excipients might be added as lubricants, binders, disintegrators, appearance enhancers as well as for identification purposes and other functions. Solid dosage forms may also be coated to maintain long-term stability and improve bioavailability. Capsules typically made from either hard or soft gelatin offer an alternate solid form formulation pathway. Capsules can be filled with powder blends, granules, or pellets, depending on the targeted release profile.
For solid dosage forms, the target formulation criteria typically ease of manufacture to give appropriate solubility and dissolution of the active molecule for a consistent and reliable therapeutic response in the patient. These formulation criteria may require substantially different formulation strategies for different polymorphs and salt forms. For example, the enhanced solubility and dissolution rate that can be achieved with some salt and amorphous actives can lead to nucleation and recrystallization within the gut and reduced bioavailability. Formulations using solid forms with fast dissolution rates may include surfactants as excipients to inhibit nucleation. This formulation approach is often referred to as springs and parachutes.

As active molecules become more complex in their properties, often with low aqueous solubility, nano-phase formulations are becoming more common. These include, for example, a self-assembling delivery systems like micelles and lipids.

Successful formulation strategies will require the extensive application of analytical chemistry methods, to monitor the blending of multiple chemical components together. The elemental and molecular purity of these various components will be a critical quality concern that can be addressed by the use of fluorescence and spectroscopic analytical methods. Throughout the blending and manufacturing process, the solid form structure of the active ingredient will also typically require monitoring by diffraction methods to ensure that polymorph conversion will not be induced by each process step. Furthermore, with multiple chemical components together, the exposure to humidity, temperature, and light may cause complex interactions that impact the therapeutic performance. Non-ambient and thermal methods can be employed to explore the phase relationships between components to help identify any future problems.