A Ferrari Without Wheels

Posted on 2nd December 2009

Pharmaceutical Products

Final pharmaceutical products are composed of the drug, which has a pharmacological activity, and excipients, which have no pharmacological activity. In addition, the product needs to be packaged in suitable containers which are adequately labeled. The mixture of excipients is called a formulation or dosage form.

Role Of Excipients

Excipients turn the drug into a useful medicine by:

• Making the drug suitable for the route of administration (e.g. tablets, capsules for oral administration; injection, infusion for intravenous formulation)
• Enabling accurate dosing; a patient cannot be supplied with a bottle of drug powder and a spoon for self dispensing. The therapeutic dose in a single dose unit, containing an accurate amount of the drug and prescribed number of dose units per day, guarantees proper treatment of diseases
• Adapting for special patient populations. For example, children and the elderly cannot be given tablets which are too big; children often refuse to accept bitter medicines so either special flavours or coated formulations may be used
• Lowering the administration sequence. Controlled release formulations may reduce the therapy to only one tablet per day
• Making the drug more active and less toxic. Excipients can increase the dissolution rate and degree of solubilization of a drug that is administered orally compared to the unformulated drug. This can increase the degree of oral absorption. The steady release of the drug from a formulation may prevent occurrence of high, toxic peak levels. Upon parenteral administration, the drug may be carried to its site of action whilst avoiding tox target organs. More active drugs require a lower dose and hence smaller tablets which is a potential marketing benefit. Gastric coating of formulations releases the drug in the duodenum to avoid decomposition or precipitation in the stomach
• Stabilizing the drug (e.g. pH, dry formulation to stop reaction with water etc)
• Enabling pharmaceutical processing. Drugs produced by chemical development may have poor flow properties and excipients are needed to improve the flow to enable capsule fills

Compatibility Of Drug With Formulation

Attention should also be paid to the characteristics of the drug to achieve an optimal compatibility with the excipients. This matching of drug with excipients is a key element to obtain formulations with optimal performance: crystal shape (needles have poor flow property), form (influences the solubility), salt form, particle size, porosity.

The Special Case Of Poorly Water Soluble Drugs

Poorly water soluble compounds cannot be administered intravenously as such. Either they should be dissolved in suitable excipients or administered in colloidal excipient carriers. Also, for oral administration it is a very exceptional case that an unformulated drug possesses flow properties and particle size suitable to obtain sufficient oral bioavailability. In practice, such drugs need to be formulated by engineering the crystals, creating a stabilized amorphous phase or solubilizing them in vehicles able to delay the precipitation upon dilution in the biological milieu.

Complexity Of Selecting The Optimal Formulation

Finding the right excipients and ratio of excipients and optimal drug load of a formulation that will yield optimal stability, compatibility and bioavailability of the resulting pharmaceutical product is a challenging task. In addition, the production process of the formulation should be amenable to scale-up and be economically viable. Intelligent excipient selection based on a deep knowledge of excipient and drug properties and long term experiences in developing formulations and the availability of a broad suite of technologies is helpful. In order to develop optimal formulations which are tailor made for the drug, extensive technological screening for formulations (e.g. compatibility, in vitro release, stability) in combination with rigorous testing of the performance of formulations in animal models (e.g. PK, oral and absolute bioavailability) is an absolute necessity.

The Need For Pharmaceutical Development

Developing drugs without paying attention to its formulation/dosage form is like building a Ferrari without wheels and carrosserie. The Ferrari cannot go anywhere and will not be approved by regulatory authorities. The precious engine inside is degraded to a lonely, miserable, worthless piece of metal. Without paying sufficient attention to formulation, an adequate pharmaceutical product simply cannot be developed.