Formulation and Delivery of Proteins and Peptides

The success of most peptide and protein drugs is dependent upon the delivery of the biologically active form to the site of action. In the design and development of formulations to achieve this goal, the formulation scientist must consider the clinical indication, pharmacokinetics, toxicity, and physicochemical stability of the drug. The development of a stable formulation is a necessary step for each new protein or peptide therapeutic. The degradation pathways and their impact on stability should be systematically analyzed and competing degradation rates must be balanced to arrive at the most stable formulation possible. Several routes of administration should also be considered and future development of new formulations may expand the number of potential options. Formulations for each route of administration may be unique and, therefore, have special requirements. In the case of depot formulations, there are many potential matrices, each of which has distinct characteristics that affect its interactions with the drug and its behavior in vivo. The formulation characteristics may have a dramatic impact on the in vivo stability of the drug as well as the pharmacokinetics and pharmacodynamics. The optimization of formulations, the routes of delivery, the design of depot systems, and the correlation between physicochemical stability and in vivo behavior are discussed in detail with recent examples. For new biotechnology-derived drugs including nucleic acids (DNA vectors and antisense RNA) to reach commercialization, all of the issues involved in the design and development of a drug formulation must be considered at an early stage of the overall development process.