Essay by Walter P. Drake, Chief Scientist, Bengal Bioscience Inc.
An Alternative Medicine Company
Bengal Bioscience will be specializing in transdermal preparations of botanicals and biomedicines. That means Through The Skin.
Everything we formulate will be similar to cosmetics in that we will be producing creams and gels. And many of our products, similar to progesterone cream, will be categorized as botanical beauty products, and as such, subject to less restrictive FDA regulations
The principle benefits of transdermal over oral administration are:
#1 No concern for insolubility and low uptake in the gut
#2 No stomach irritation or upset
#3 No first pass through the liver where compounds are metabolized and degraded
#4 Direct entry into the blood stream after application and penetration through the skin
#5 But the most spectacular benefit is that once in the blood stream, the botanical compound or any other biomedicine can create systemic benefits, not just be localized at the site of application.
The above is an illustration of the three skin penetration pathways. Topically applied creams and gels can penetrate the skin in one of three different ways: (1) through the appendageal route (Hair Follicles, and sweat glands); (2) through the intracellular route, or (3) through the intercellular route. The intracellular route involves a direct path through the cell membrane of multiple layers of the epidermis. The intercellular route involves a more tortuous path between epidermal cells. The pathway taken likely depends on the size, charge, morphology, and material. [Adapted from Palmer, BC and DeLouise LA, “Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting”, Molecules 15:21 (2016).]
I am going to show you one graph to illustrate how the transdermal delivery of drugs and biomedicines is far superior to oral administration or injectables. In this experiment, the oral adminstration of progesterone at 200 mg/day was compared to the topical application of 40 mg progesterone cream in a sample of postmenopausal women. The purpose of the study was to see if the topical application was as effective as taking a pill. You will note on the following graph that not only did the topical application result in a steady level of pregesterone in the blood, but the oral route resulted in an unwanted, dangerous spike in the level of progesterone in the blood. Click on picture to make bigger:
Now, what else can be learned from this graph? By eliminating the large first pass through the liver, where the oral progesterone must be taken up by the gut and then metabolized into break-down products by the liver prior to entering the blood stream, we see that only 40 mg of progesterone in the cream gives the same systemic concentration in the blood as a 200 mg pill! Moreover, we see that the topical cream results in a sytemic whole body treatment, and is not just localized to the site of application. [Hermanne, AC et al, “Over-the-Counter Progesterone Cream Produces Significant Drug Exposure Compared to a Food and Drug Administration–Approved Oral Progesterone Product”, J.Clinical Pharmacology 45:614-619 (2005)]
In another study, topical application of Viagra was compared to delivery of the drug via a topical cream. Again the topical application was superior, avoiding dangerous spikes and yielding a steady state blood stream concentration. The authors state: “Repeated doses of oral sildenafil are required to sustain plasma levels because of its short duration of action with high liver metabolism. Thus, topical delivery through local tissue area may be an alternative to oral administration to reduce the incidence of adverse effects, increase the time to onset of response, and sustain effects for longer periods. Furthermore, transdermal delivery of sildenafil can offer several advantages over conventional dosage forms and the multiple dosing can be eliminated”. Yonessi M and Saeedi M, “A Double-blind Placebo-controlled Evaluation of the Effect of Topical Sildenafil on Erectile Dysfunction”, J Applied Research, 5(2): 289 (2005).
The authors go on to note another two very important characteristics of the transdermal route:
(1) Transdermal Viagra enters the blood stream and causes erection within 7- 15 minutes, and
(2) More than 90% of the drug was found in the blood stream within 1.5 hours of topical application, showing that a topical application caused a systemic effect.
This beneficial steady stream of activity shown in these two studies is the most common observation for topical creams and may be the reason why the entire pharmaceutical industry is moving rapidly to catch up to this methodology.
All Bengal Bioscience, our products under development are formulated as creams for topical application because not only do penetrating creams ensure that the compound is administered, but also because the end result is a systemic benefit, not just local to site of application. And with this technique, we eliminate insolubility issues, poor gut uptake which is low bioavailability, first pass liver metabolism, and stomach irritation, and get a steady stream of beneficial compound into the blood.