Molecular mass biopharmaceuticals

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

Pulmonary delivery currently represents the most promising alternative to parenteral delivery systems for biopharmaceuticals. Delivery via the pulmonary route moved from concept to reality in 2006 with the approval of Exubera, an inhalable insulin product (Chapter 11). Although the lung is not particularly permeable to solutes of low molecular mass (e.g. sucrose or urea), macromolecules can be absorbed into the blood via the lungs surprisingly well. In fact, pulmonary... 

Table 7.4 The molecular mass of some polypeptide biopharmaceuticals. Many are glycosylated, thereby exhibiting a range of molecular masses due to differential glycosylation...

This is the consequence of the traditional application of CE in the process and product monitoring of rDNA-derived biopharmaceuticals in biotechnological industries. However, related proteins, and dimer and related substances of higher molecular mass of somatropin, and aprotinin are evaluated by means of HPLC and size exclusion chromatography, respectively, by the EP. 

The molecular mass of most biopharmaceuticals is considerably less than 100 kDa (Table 3.28). The proteins would thus elute from gel-filtration columns much later than contaminating... 

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