5.5.5.3 Adsorption
Peptide and proteins have a tendency to adsorb to surfaces, and this can pose a significant problem in their delivery. This is especially true with an intravenous infusion because the administration set provides a huge surface area on which adsorption may take place. Furthermore, most biotechnology-
derived proteins are very potent, so doses are very low. Thus, even small amounts of adsorption may lead to a significant loss of drug. Adsorption may also occur on an in-line filter in an administration set. When an in-line filter was added to an IV administration set for the delivery of IL-2, almost all the drug was lost. Adsorption of insulin to glass and other materials has been investigated in several studies.(124–126)
Adsorption depends on the concentration of insulin, contact time with the surface, and the formulation. If insulin is administered from a syringe as a concentrated solution, the loss because of adsorption may not be significant. However, at low concentrations, the loss caused by adsorption can
be significant. Such low concentrations will often be encountered with infusions. In this case, the flow rate of the infusion will also influence the extent of adsorption. When infused from Viaflex containers, as much as 23% of insulin was found to be adsorbed during the first 30 min of infusion.(127) Petty and Cunningham(128) found that when they added 30 units of insulin to 1.0 L Ringer’s lactate solution, the patient received only 6.36 units of insulin because of losses by adsorption. More than 50% of insulin was adsorbed by glass and polyvinylchloride containers within 15 sec of injection. Of the remaining amount, another 50% was lost by adsorption to the intravenous infusion set. Adsorption of insulin to glass was reduced but not eliminated by the addition of albumin. In practice, therefore, addition of albumin may or may not be effective because insulin may quickly adsorb to the infusion set and reach an equilibrium. Also, it should be realized that the rate of insulin infusion may be
adjusted to the blood glucose response, and thus insulin lost through binding may become less important. Colony stimulating factors filgrastim (G-CSF) and sargramostim (GM-CSF) are also known to bind to infusion containers. It has been reported that if the final concentration of filgrastim is between 2 and 15 mg/ml, 0.2% human serum albumin must be added to prevent adsorption to the infusion container. Because these colony-stimulating factors are very expensive, the cost of albumin in comparison is justified.(129) IL-1b has also been reported to adsorb to plastics at low (100 ng/ml)
concentrations. The addition of 1% human serum albumin was found to prevent such adsorption. However, at higher concentrations (1 mg/ml), IL-1b could be stored and delivered from either polypropylene-based syringe pump delivery systems or polyvinyl chloride (PVC) infusion bags for up to
24 h.130 Adsorption of D-Nal (2)6 luteinizing hormone-releasing hormne
Chapter Five: Lyophilization, Pharmaceutical Processing 167
(LHRH) on glass, plastic, tubings, syringes, and filters was found to reach a steady state within 2 h. Prevention of this adsorption by ionic compounds, inert proteins, or amino acids was investigated. Of these, phosphate and acetate ions were found to be most effective.131 Plasma proteins are also
known to adsorb to polymeric surfaces,132–135 and this may have relevance to the use of PVC and silastic surfaces in vivo or in any situation when a polymer is in contact with blood. Other aspects of adsorption, such as principles and mechanisms, are discussed in Chapter 3; adsorption to the filter during pharmaceutical processing is discussed in Section 5.2.1.
