Strategy formulation

Three formulation strategies based on having a high-resting-state viscosity after filling have been described [161,162] ... 

Formulation strategies for stabilization of proteins commonly include additives such as other proteins (e.g., serum albumin), amino acids, and surfactants to minimize adsorption to surfaces. Modification of protein structure to enhance stability by genetic engineering may also be feasible, as well as chemical modification such as formation of a conjugate with polyethylene glycol. 

A variety of approaches exist for stabilizing proteins, for example, chemical modification, immobilization, and site-directed mutagenesis [95,96], but these techniques are not within the scope of this chapter. The focus here will be on stabilization of proteins via formulation development. The principal formulation strategy is to stabilize the protein using clinically acceptable additives (excipients) or through the use of suitable pharmaceutical-processing technologies. 

Such relationships are important to note because they can help us to formulate strategies for further research. The benefit of multiple, rather than one-off analyses is also evident. However, it is unlikely that the lines... 

M. Cholewinski, B. Ltickel, H. Horn, Degradation Pathways, Analytical Characterization and Formulation Strategies of a Peptide and a Protein. Calcitonin and Human Growth Hormone in Comparison , Pharm. Acta Helv. 1996, 71, 405-419. 

Figure 13.7 A formulation strategy using microcalorimetry aimed at deriving stable liquid candidates.

Jason Kindrachuk is a postdoctoral fellow at the University of British Columbia (UBC) in the laboratory of Professor R. E. W. Hancock. Jason received his Ph.D. from the University of Saskatchewan in 2007 where his research focused on host and pathogen sensory systems. During his study he specially focused on TLR-9 receptor—ligand interactions and the interactions between host defense peptides and the PhoPQ two-component sensory system of Salmonella typhimurium. In 2008 Jason received the Canadian Cystic Fibrosis Foundation Kin Canada Fellowship for his research in the area of alternative therapies for treatment of antibiotic- and multidrug-resistant bacteria. Currently his research is focused on the investigation of structure-activity relationships amongst natural and synthetic host defense peptides from the perspective of associated immunomodulatory activities and as well as vaccine formulation strategies. 

Figure 1 Summary of the suitability of various formulation strategies to drugs in individual Biopharmaceutical Classification System classes.

Specific formulation strategies need to be employed for macromolecule compounds. An excellent review of protein stability in aqueous solutions has been published by Chi et al. (92). In addition to solution stability of proteins and peptides, aerosolization may result in significant surface interfacial destabilization of these compounds if no additional stabilization excipients are added. This is due to the fact that protein molecules are also surface active and adsorb at interfaces. The surface tension forces at interfaces perturb protein structure and often result in aggregation (92). Surfactants inhibit interface-induced aggregation by limiting the extent of protein adsorption (92). 

Figure 3 Formulation strategies for delivery of water-insoluble drugs.

Formulation Strategies and Practice Used for Drug Candidates with Water-Insoluble Properties for Toxicology, Biology, and Pharmacology Studies in Discovery Support... 

Formulation Strategies and Practice Used for Drug Candidates... 

Maas, J., W. Kamm, and G. Hauck (2007). An integrated early formulation strategy-From hit evaluation to preclinical candidate pro ling.ur. J. Pharm. Biopharm., 66 1-10. 

Aungst, B.J. (1993). Novel formulation strategies for improving oral bioavailability of drugs with poor membrane penetration or presystemic metaboliterfi wm- Sci., 82 979-987. 

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