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Next I started reading some abstracts of two sets of lectures on drug release mechanisms given by European pharmacy professors who are members of the Controlled Release Society, which I found at: http://www.medfarm.unito.pharmaco/itcrs/erasmus/erasma.html given in 1995 and http://www.unipr.it/arpa/dipfarm/erasmus/erasma.html given in 1996. Among these the "Methods for evaluating the in vivo fate of solid dosage forms" by Prof. Moes of the Free University of Belgium seems to have particular relevance. But here I ran into trouble. All the web materials from these lectures are highly technical and condensed. Yet there were a few points which I seem to have almost understood enough to ask questions about. I'm sure that I'll be taking things out of context, but it's only in an attempt to call attention to what I think needs to be considered. The Professor describes the use of gamma scintigraphy to track the "gastrointestinal transit of solid dosage forms, particularly non-disintegrating single-unit and multiple-unit sustained-release forms." Determinations were made of such events as Gastric Residence Time (GRT) and Small Intestinal Transit Time (SITT). Occasional stagnation at the ileo-caecal junction was observed. It was found that "The small intestinal transit of pharmaceutical dosage forms is remarkably short (3 +/- 1 h) and constant, irrespective of the fed or fasted state of the subjects and of the type of dosage form ingested." There seem to be problems with solid CR dosages at certain points in the cycle. "In fasting conditions, the GRT of non-disintegrating monolithic dosage forms (coated tablets, matrix tablets, osmotic tablets, hydrophilic matrix capsules...) is highly variable and totally umpredictable (10 to 120 minutes). It depends on the coincidence of dosing with the occurrence of the IMMC phase III [the climax of the intradigestive migrating motor complex?]. The GRT of such single-unit forms may be as long as 10 hours when they are dosed after a high fat meal (the GRT enhancement depends on the calorific value of the meal)." ...... "From all these observations, we can conclude that one can hardly rely on a predictable and reproducible time span to define the delivery life-time of solid oral controlled-release dosage forms." "Thus, it appears that the drug absorption in the GI tract may be highly variable since the period of time available for drug delivery completion is unpredictable and may be very short in certain circumstances." Controlled release mechanisms of various forms are still being worked on, and the solid dose form, represented by sinemet CR, may not be the last word or the best delivery form. Until better forms appear, I wonder whether there are times in the various phases of the digestive and intradigestive processes when small frequent doses of regular sinemet might be better than CR. Has anyone looked at this possiblity? Or am I best off somehow adapting my food cycle to the limitations of my pill cycle? Phil Tompkins Hoboken NJ age 60/dx 1990