Lack of baseline dissolution data makes evaluating risk of bioavailability enhancements tricky, researcher says
Bill Gurley, PhD, gave an address at the recent 15th Annual Oxford International conference on the Science and Regulation of Botanicals put on by the National Center for Natural Products Research. Gurley, who is a professor at College of Pharmacy at the University of Arkansas for the Medical Sciences, gave a talk on the benefits and risks of the various approaches to improving phytochemical biovailability. It is a subject that responsible suppliers have been wrangling with almost from the outset of the modern dietary supplement industry, he said.
“Almost from their start dietary supplements have been criticized for their questionable efficacy,” Gurley said.
Lack of baseline data
The complex and evolving nature of dietary supplement ingredients based on phytochemicals has been a confounding factor both for assessing efficacy. While some sources indicate the situation is improving, all too often studies on herbal ingredients are lumped together under the scientific and/or common names of the herbal material, without taking into account the many different dosage forms these ingredients can take and the resulting difference (sometimes by an order of magnitude) in how well they cross the barrier into the blood stream.
“The medical literature is awash in conflicting studies. But one very simple and often overlooked aspect is a failure to characterize proper dosage form performance in these studies,” Gurley said.
That hazy picture also clouds the view of the pharmacokineticist interested in assessing risk, which could include possible drug/herb interactions, Gurley said. Standards for botanical ingredient identity and testing parameters
“Very little is known about the pharmacokinetics of most of these phytochemicals. Caffeine and the ephedrine alkaloids are notable exceptions,” he said.
Missing dissolution standards
In particular, Gurley said, very little public information is available on the dissolution profiles of many leading ingredient categories. It’s not one of the areas touched upon in depth by existing regulations.
“GMPs do not require dissolution or disintegration testing,” Gurley said. “Dissolution standards have not been established for most of the USP botanical monographs.”
With that backdrop of uncertainty concerning even garden-variety botanical ingredient forms, Gurley gave a rundown on the major approaches to boosting the uptake of these usually hard-to-absorb compounds, which include:
• Lipsomes
• Phytosomes
• Self emulsifying drug delivery systems
• Nanoparticles
• Phytochemical inhibitors of xenobiotic metabolism, such as piperine.
Potential for a nasty surprise
The issue for Gurley, who is also a member of the United States Pharmacopoeia’s Expert Panel on Dietary Supplements, is that the details about the boost these technologies provide to the ingredients to which they are applied is not always known to someone in his position, making evaluating cases of possible liver toxicity and potential negative herb-drug interactions tricky. In this era when even the most basic regulatory relationships and assumptions are being questioned in the mainstream media, Gurley said this is a shortcoming that constitutes yet another weakness in the current framework.
“There are a lot more of these new formulations that will be coming onto the market pretty soon that might catch us by surprise for herb-drug interactions. More information is needed and it should be gathered using the best available analogues for gastric or intestinal fluid,” Gurley said.
