Human growth hormone formulation

Agerholm, C., et al. 1994. Epithelial transport and bioavailability of intranasally administered human growth hormone formulated with the absorption enhancers didecanoyl-L-alpha-phospha-tidylcholine and alpha-cyclodextrins in rabbits. J Pharm Sci 83 1706. 

J. L. Cleland and A. J. Jones, Stable formulations of recombinant human growth hormone and interferon-y for microencapsulation in biodegradable microspheres, Phar. Res, 13(10), 1464 (1996). 

Pikal, M. J., Dellermann, K., Roy, M. L Formulation and stability of freeze-dried proteins Effects of moisture and oxygen on the freeze-dried formulation of human growth hormones. Developments in Biological Standardization, Vol. 74, p. 21-38. Acting Editors Joan C. May - F. Brown. S. Karger AG, CH-4009 Basel (Switzerland), 1992... 

Leitner VM, Guggi D, Bernkop-Schnurch A (2004) Thiomers in noninvasive polypeptide delivery in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone. J Pharm Sci 93 1682-1691. 

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 13.8. Effects of route and sustained release formulation on the time course of human growth hormone concentration in plasma. Shown is the average time course of human growth hormone (hGH) in plasma after intravenous (0.02mg/kg) and subcutaneous (0.1 mg/kg) administration in humans. Arrows indicate weekly subcutaneous dosing of hGH in solution. A single dose of the same protein formulated in polylactide-co-glycolide (PLG) microspheres (0.75 mg/kg) given subcutaneously sustains human growth hormone levels in plasma for at least one month.

Type IV poly(ortho esters) are very similar in structure to type II poly(ortho esters), but they do not need to have excipients in the formulation due to the incorporation of no acidic moieties in the polymer backbone (Ng et al. 1997). Rods of poly(ortho ester) loaded with recombinant human-growth hormone and bovine serum albumin have been created. The rods are the products of polymer-protein mixture extrusion at a temperature between 50° and 70°C. Particles have also been produced from these rods (Heller et al. 2000). The size of these particles, >106 pm, was much larger than would be expected to be absorbed by the gastrointestinal lining (Florence 1997). If the particle size can be reduced, this type of polymer system may be made to be acceptable for oral administration. 

Cheng, Y.-H., Dyer, A. M., Jabbal-Gill, I., Hinchcliffe, M., Nankervis, R., Smith, A., and Watts, P. (2005), Intranasal delivery of recombinant human growth hormone (somatro-pin) in sheep using chitosan-based powder formulations, Eur. J. Pharm. Sci., 26, 9-15. 

Wielburski, A. (1991). Genotropin-recombinant human growth hormone. In Polypeptide and Protein Drugs Production, Characterization and Formulation. R.C.Hider and D.Barlow, eds. (Chichester EUis Horwood), pp. 197 210. 

M. J. Pikal, K. Dellerman and M. L. Roy, Formulation and stability of freeze-dried proteins effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone. Dev. Biol. Stand. 74. 21-38 (1991). 

Storage stability has generally been the more serious stability issue faced with therapeutic proteins. Storage stability can be extremely formulation-specific [15,30,32,33], and even with a knowledge of the major degradation pathways in solution, selection of the optimum formulation for a solid is far from obvious. We illustrate the sensitivity of stability to formulation details with studies of an important protein product, human growth hormone. 

Figure 5 Effect of excipients on the storage stability of freeze-dried human growth hormone (hGH). Samples were stored for I month at 40°C. Solid bars, aggregation (primarily dimer). Hatched bars, chemical degradation via methionine oxidation and asparagine deamidation. The glass transition temperatures of the initial freeze-dried formulations are given above the bars when a gla.ss transition temperature could be measured by DSC. The glycine mannitol formulation is a weight ratio of hGH glycine mannitol of 1 1 5, the dex-tran formulation is 1 6 hGH dextran 40, none means no stabilizer, and the others are 1 1 hGH stabilizer. All formulations contain sodium phosphate buffer (pH 7.4) at 15% of the hGH content. Initial moisture contents are all ==1%. (Data from [4].)...

Pikal et al. [33] also looked at effects of moisture and oxygen on the formulation and stability of freeze-dried human growth hormone evaluating the formation of irreversible aggregates. 

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