Peptide formulations

M. F. Powell, L. M. Sanders, A. Rogerson, V. Si, Parenteral Peptide Formulations Chemical and Physical Properties of Native Luteinizing Hormone-Releasing Hormone (LHRH) and Hydrophobic Analogues in Aqueous Solution , Pharm. Res. 1991, 8, 1258 -1263 ... 

Powell, M.F., Sanders, L.M., Rogerson, A., and Si, V., Parenteral peptide formulations ehemi-eal and physieal properties of native luteinizing hormone-releasing hormone (LH-RH) and hydrophobie analogs in aqueous solution, Pharm. Res., 8 1258-1263 (1991). 

The introduction of safe, effective absorption-enhancing agents represents the critical element limiting the widespread use of nasal peptide formulations. Progress in this area has been slow to date, but several agents appear to have the potential to enable consistent and efficient absorption of peptide drugs from the nose. 

A bioerodible micro/nano particle technology used in the development of oral protein and peptide formulations. 

Table 2 Some examples of excipients used as protectants for freeze-dried protein and peptide formulations...

Freeze-Dried Products. Freeze drying was first carried out in 1890 by Altman but became well known through the industrial development of the process. The process is used in the food industry, e.g., for the production of instant coffee, tea, and other products. In the field of pharmaceutical technology, it was for a long time restricted to only few formulations for injection containing the active ingredient in the freeze-dried state in an ampoule to be dissolved just before application. With the increasing interest in protein and peptide formulations, freeze-dried products became more important. These are discussed under section Microparticles for Injection. ... 

Prevention of deamidation If the deamidation occurs by a general acid-base mechanism then the optimum pH for a peptide formulation will usually be about 6, where both rates are at their minimum. If the deamidation occurs through the cyclic imide intermediate it is, in principle, preferable to formulate at a low pH since this type of deamidation is base-catalysed. This may not be feasible in practice, however, since other routes of degradation tend to predominate at lower pH and a compromise must then be sought. It is well established that deamidation rate may be affected markedly by buffer components and hence care must be taken in the choice of buffer used in the control of pH. In general it is found that the phosphate anion is most problematic in its effect on the rates of deamidation. 

Shahrokh Z. Developing Pharmaceutical Protein Formulations Assumptions and Analytical Tools. In Shahrokh Z, Sluzky V, ClelandJ, Shire S, Randolph T (eds.), Therapeutic Protein and Peptide Formulation and Delivery. ACS... 

Moriyama K, Ooya T, Yui N Hyaluronic acid grafted with poly(ethylene glycol) as a novel peptide formulation, J Control Release 1999, 59, 77-86. 

Niu G-H, Chiu Y-Y FDA Perspective on peptide formulation and stability issues,... 

Constantino HR, Liauw S, Mitragotri S, et al.. The pharamaceutical development of insulin historical perspectives and future directions. In Shahrokh Z, Sluzky V, Cleland JL, et al., Eds. Therapeutic protein and peptide formulation and delivery. American Chemical Society Symposium Series, Washington DC, American Chemical Society 1997 675 29-66. 

Of all the mucosal, nasal mucosa is considered to be the most permeable, offering tremendous scope for peptide delivery, particularly for vaccines (90% of pathogens invade via mucosa).Already, several peptide formulations are on the market, and further developments will depend on clarifying the immunogenicity of bioactive agents on the nasal mucosa and the long-term effect of enhancers on the nasal mucociliary activity. 

Studies in several laboratories have shown that strongly hepatotoxic cyclic heptapeptides of a common type occur in different strains of Microcystis [59]. Microcystis aeruginosa, the species most frequently investigated contains the peptide formulated in Fig. 25. The two letter suffix LA designates the two L-amino acids in positions 2 and 4 (X, Y = Leu, Ala) which have been found variable in all of the toxins examined to date. X can also be arginine (R) or methionine (M). The 10-carbon chain jS-amino acid is unique for this type of hepatotoxic compound. Another not quite common structural element is the unsaturated side chain of dehydroalanine (No. 7), the formation of which can readily be imagined by elimination of H2O from serine or H2S from cysteine. 

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