Hi,
Time release capsules ( the FDA regards both sustained and prolonged
release formulations as extended release dosage forms ), are
engineered by using various types and layers of coatings around the
active substances, which dissolve at various times and areas of the
body. That's the theory. For example, aspirin is normally has a
special coating termed an enteric coating, which is resistant to
stomach acid and dissolves in the high pH of the intestines. The
purpose of this coating is to prevent dissolution of the tablet in the
stomach, where the stomach acid may degrade the active ingredient, or
where the time of passage may compromise its effectiveness, in favor
of dissolution in the small intestine, where the active principle is
better absorbed.
In humans, the stomach is a highly acidic environment (maintained by
the secretion of hydrochloric acid) with peptidase digestive enzymes.
In fact, the stomach's interior can secrete 2 to 3 liters of gastric
fluid per day. The pH of gastric acid is 2-3 in the stomach lumen (The
pH of the stomach may go as low as 1.0. This is a very acidic level.
Because the pH scale is a logarithmic scale, the pH of the stomach is
much stronger than typical cellular fluids which are generally close
to 7.0 (the neutral level on the pH scale.) When food comes into the
stomach, the pH may rise to levels between 3.0 and 4.0 due to the
buffering capacity of proteins.). The parietal cell releases
bicarbonate into the blood stream in the process, which causes the
temporary rise of pH in the blood, known as alkaline tide. Even after
meals of fatty foods and habanero sauce the pH level of the stomach
environment is not going to change much around these parameters.
There are several safety mechanisms that prevent higher pH levels and
damage to the system. Nonetheless, when due to different reasons these
fail (e.g. because of excess acid production), this can lead to
heartburn, a burning in the stomach or peptic ulcers.
As far as disease goes in hypochlorhydria and achlorhydria, the
parietal cells are unable to produce the required amount of gastric
acid in the stomach, potentially leading to gastroenteritis. Also the
disinfectant properties of the gastric milieu are decreased, leading
to an increased risk of infections of the digestive tract (such as the
foodborne infection with Vibrio vulnificus).
In Zollinger-Ellison syndrome and hypercalcemia, there are increased
gastrin levels, leading to excess gastric acid production, which can
cause ulcers.
In diseases featuring excess vomiting, patients develop hypochloremic
metabolic alkalosis (decreased blood acidity by H+ and chlorine
depletion).
With chronic pancreatitis the pH levels of the upper small intestine
is 2.2 to 2.4. Postprandial gastric pH levels 2.9 to 3.2. Postprandial
upper small intestine pH levels 5.1 to 5.5
I'm pointing out this level of pH and the levels where the body begins
to have severe problems to illustrate the point that; if you are not
within these levels, you are probably not worried about time release
capsules. Medications are now being put directly into your blood
stream by a professional medical staff. The human body is just not
that capable dealing with sever changes in the pH levels. So while the
conditions you are talking about do change the pH levels (or at least
have some effect on them) the amount of changes we are talking about
before critical levels are seen, are not great.
With any change of course there would be differences in the amount of
time that various parts of the body could dissolve various substances.
The guidelines are pretty ridge and the tests for specific pH levels
or specific substances are very narrow with both the FDA and Europa's
guidelines, given to specific pH levels
For Example :
" The test medium should preferably be aqueous-based; organic or
aqueous-organic media should be avoided. For poorly soluble
substances, a minimal content of an appropriate surfactant may be
added. Buffer solutions at a number of pH values spanning the
physiological rate (pH 0.8-2, stomach; pH 5-6.5, jejunum; pH 6-7.5,
ileum; Davis et al 1989) should be used to determine the relationship
between dissolution and pH. The data obtained could usefully be
represented using three-dimensional dissolution profiles (i.e. %
dissolved as a function of time and pH)."
So the ranges of testing are narrower than the human body's range can
be on any given hour of the day, however, the range the body can
extend to at any given hour of the day is not much greater without
running into sever problems. Also, extreme range changes in the body's
pH level (digestive or over all), do not last very long (again,
without having sever problems or resulting in death).
References :
FDA's Guidance for Industry
Extended Release Oral Dosage Forms:
Development, Evaluation, and Application of In Vitro/In Vivo Correlations
[ http://www.fda.gov/cder/guidance/1306fnl.pdf ]
Other Guideance Documents from FDA
[http://www.fda.gov/cder/guidance/index.htm ]
Europa's QUALITY OF PROLONGED RELEASE ORAL SOLID DOSAGE FORMS
[ http://pharmacos.eudra.org/F2/eudralex/vol-3/pdfs-en/3aq19aen.pdf ]
Stomach - Wikipedia
http://en.wikipedia.org/wiki/Stomach
Gastric acid - Wikipedia
http://en.wikipedia.org/wiki/Gastric_acid
Entrez PubMed
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7585849&dopt=Abstract
USDA
[www.ams.usda.gov/fqa/aa20346.pdf ]
Thanks,
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