General Pharmacological Considerations

This article [Horter and Dressman, 2001: (http://www.ncbi.nlm.nih.gov/pubmed/11259834)] is really interesting, and the authors noted, on the last two pages of text, that the gastric luminal fluid volume can be only 20-30 mL in the fasted state (meaning that the person hasn't ingested anything for 12+ hours, though 14.5 hrs may be required for the stomach to completely empty) and that the USP procedures for evaluating tablet dissolution had been based, at the time the authors wrote the article, in 2001, on nonphysiological pH values (7.5 is not a pH value that's likely to be reached in the GI tract in many people) and surfactant concentrations. The authors also discussed the fact that the rate of dissolution is frequently the most important factor determining the rate of absorption (and, hence, the bioavailability, in many cases). The issue of the luminal fluid volume can be important in determining the rate of dissolution, and the authors noted, for example, that increases in the viscosity of the intestinal luminal fluid, such as in response to food intake, can slow the rate of dissolution and, hence, the rate of absorption. In general, if one wants to maximize the bioavailability of a physiological substance, one should take it on an empty stomach. One might want to spread the total daily dosage out across the day, but it's worthwhile to keep these types of things in mind.

Maximizing bioavailability is not likely to be very important for many supplements, especially if they're in capsule form, etc. For example, I don't think there's any need to try to maximize the bioavailability of encapsulated creatine monohydrate, given that a slight increase in bioavailability is not going to be very important. But, in the case of purine (and pyrimidine) nucleotides, for example, the half-life is extremely short, and the elevation of the concentration of the nucleotide or its metabolites (i.e. other purines) in the systemic circulation is extremely brief, following oral administration. There can be drastic changes in the bioavailabilities of nucleotides, in response to small changes in the rate of dissolution and absorption. Small changes in those parameters have the potential to produce large changes in the bioavailability.

In a related vein, there are still many reports, from articles in the literature and from other sources, of problems with the dissolution of supplements provided in tablet form. It's still a significant problem in the supplement industry, in my opinion. In this context, the issue is not just bioavailability but absorption. If a tablet doesn't dissolve, the absorption and bioavailability will be zero. Consumerlab.com has shown that some tablets essentially don't dissolve at all, and they suggest this complex method for telling if a tablet is going to dissolve (http://www.consumerlab.com/results/hometest.asp). I don't think that's necessary. If a tablet is going to dissolve properly, in my opinion, it should dissolve in a small glass of water in a few minutes. When tablets truly meet dissolution standards, they dissolve in a minute or less. Several years ago, I looked at a lot of reports from Consumerlab.com. They reported that some tablets couldn't be broken with a hammer, and I remember testing some tablets (by putting them in a glass of water) and finding that some of them required 2-3 hours to dissolve. That's obviously not acceptable. I think Consumerlab.com still has some free reports, but I'm not sure. I haven't looked at the site for a few years. A lot of tablets dissolve perfectly, but it's worthwhile to just put a tablet or softgel in a glass of tap water, in my opinion (if one is planning on taking the tablet). I'm saying that that's a way to test if one "sample" tablet of that particular product, from a particular manufacturer, is going to meet some rudimentary dissolution test. If it does, for example, then there's no need to think about it again. In general, though, the dissolution of capsules tends to be more reliable, in my opinion, than the dissolution of those other dosage forms.