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