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Skip to 0 minutes and 14 seconds Let’s look at the formulation approaches that we can use to improve bioavailability. First to increase the permeability to the absorption barrier, and for that, we can either Surfactant, Liposome or Iontophoresis. Or to decrease the enzymatic activity at the site of absorption. And to enhance resistance to degradation by structural modification.

Skip to 0 minutes and 52 seconds Or to prolong the release of the drug at the site of absorption. And a last resort, core administration was protease inhibitor but this is the last resort. Because biologically, typically are not recommended for core administration with other drugs . Let’s look at this example of surfactant effect of nasal bioavailability. Here we have five molecular entities with amino acid or a number of amino acid ranging from 29 to 191. Now without surfactant, in this case, is a glycocholate without surfactant, the bioavailability is very low for all molecular entities. Less than one percent. But with surfactant, with glycocholate, you can tell, you can see the bioavailability has increased significantly, particularly for this smaller molecular weight glucagon.

Skip to 2 minutes and 11 seconds However, for the larger molecular weight or once the amino acid exceed a certain limit, the surfactant has limited effect. Here in this case, for the growth hormone (met-hGH) is only seven to eight percent. Let’s look at another example. This is transdermal absorption of a peptide hormone. The y-axis is the plasma concentration of the hormone. Given intravenously, subcutaneously and transdermally And by looking at the blood levels, you can tell that the TDS or the transdermal delivery system is a very good alternative to the IV and SC route of drug administration. The transdermal patch is configured as an iontophoretic transdermal patch. And let’s look at the configuration.

Skip to 3 minutes and 18 seconds By the way, the basic principle for the iontophoretic transdermal delivery is that proteins or peptides are charged molecules. And that they migrate under the inference of electric field. So let’s look at the bottom view. You have the positive electrode which is consisted of the drug or the biologics. And the negative electrode is consisted of the vehicle. And at the top view here you have the battery compartment. And here you had the activation button so when the activation button is pressed the electrical field is established. Then the biologics is driven from the positive end to the negative end that is crossing the skin

Improving Bioavailability

Oral administration would be the most convenient and preferred method of drug administration, however, it is currently not possible for biologics. Instead, IV infusion and subcutaneous injection are commonly adopted routes of biologics administration. Technologies are still challenging, but alternative routes such as transdermal, inhalation, nasal and buccal are increasingly being researched. With numerous biologics coming off patent, development of novel delivery technologies and formulation techniques can be effectively leveraged by biosimilar developers to carve a niche and gain an edge over others in the competitive biopharmaceutical industry.

Physiological barriers in the gastrointestinal tract severely limit the systemic absorption of biologics. In principle, biochemical and formulation approaches can lead to increased permeability or deceased enzymatic activity in the gastrointestinal environ. While oral administration is most preferable, other alternative routes may be considered Here the nasal absorption of several peptides are demonstrated with greater bioavailability via the incorporation of a surfactant-glycocholate In addition, transdermal absorption via iontophoresis also appeared to be a viable alternative route compared to IV and SC.

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This video is from the free online course:

Pharmacotherapy: Understanding Biotechnology Products

Taipei Medical University