Hello Vitaman,
Your question, as asked, is very broad in scope, and is affected my
numerous factors, such as humididity, stomach pH, capsule coating,
capsule contents, the packing of the contents, etc. ?Magnesium
stearate (less than 1%) can be added to powders to increase their
"flowability" which makes filling capsules easier. However, magnesium
stearate is a hydrophobic compound and may interfere with the
dissolution of the powders.?
?Increasing the concentration of the polymer in a matrix system
increases the viscosity of the gel that forms on the capsule surface.
Therefore, an increase in the concentration of the polymer used will
generally yield a decrease in drug diffusion and drug release. An
increase in the concentration of polymer also tends to put more
polymer on the capsule surface. Wetting is more readily achieved so
gel formation is accelerated.?
There are several comparison charts of hard gelatin capsule
dissolution rates, in water and HCL, on this site:
http://pharmlabs.unc.edu/capsules/text.htm
Three minutes to greater than four hours is the time needed to
dissolve gelatin capsules, depending on the coating and fill liquid.
Five to 15 minutes appears to be the average time, however, for a
gelatin capsule to dissolve in the stomach. Gelatin capsules are used
more for pharmaceuticals, while vegetable/cellulose capsules are a
favorite of herbal and vitamin markets.
This page is loaded with data regarding disintegration variables of capsules.
http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=162
?There is not enough information available about the bioavailability of drugs
from HPMC capsules to be regarded as interchangeable with gelatine capsules.
Therefore, the main objective of the present thesis was to evaluate the
biopharmaceutical properties of HPMC capsules made by Shionogi Qualicaps
S.A. in comparison with hard gelatine capsules. Both in vitro drug release and in
vivo oral and rectal bioavailability of the model drugs, ibuprofen and
metoclopramide hydrochloride, were investigated. The capsules were diluted with
either lactose or HPMC powders of different viscosities.
The overall conclusion of the studies reported here was that the HPMC and
gelatine capsule shells could be regarded as interchangeable for both oral and
rectal administration regardless of the model drug or the diluent used.?
?The stability of a water-unstable drug in HPMC and gelatine capsules has been
tested with acetylsalicylic acid (Ogura et al., 1998). HPMC and gelatine capsules
filled with acetylsalicylic acid alone were stored at 60?C for two
weeks. The drug content did not decrease to less than 95% of its
initial concentration when stored in the HPMC capsules, whereas it
decreased to 85% of its initial concentration when stored in the
gelatine capsules, apparently as a result of hydrolysis. Thus, due to
the naturally low moisture content of the HPMC capsule shells, they
are more suitable than gelatine capsules for use with formulations
containing waterunstable drugs.
Another notable difference between HPMC and gelatine capsule shells is that
HPMC capsule shells are compatible with most filling materials, since the only
incompatibility known for HPMC is the interaction between some oxidizing
agents (Harwood, 2000). Gelatine, on the other hand, has chemically reactive
groups.?
http://ethesis.helsinki.fi/julkaisut/far/farma/vk/honkanen/biopharm.pdf
?The concept of using pH as a rigger to release a drug in the colon is
based on the pH conditions that vary continuously down the
gastrointestinal tract. Times dependent drug delivery systems have
been developed that are based on the principle to prevent release of
drug until 3-4 h after leaving the stomach.?
http://www.ualberta.ca/~csps/JPPS6(1)/S.Chourasia/colon.htm
?The lag time increases with increasing coating level and higher
amounts of talc or lipophilic plasticizer in the upper layer, and a
rapid release rate after the lag phase was achieved with increased
concentration of the osmotic active agents. In vivo studies of the TES
with an in vitro lag time of 3 hours showed first drug blood levels
after 3 hours and maximum blood levels after 5 hours 28. A
combination of osmotic and swelling effects was also used in the
so-called Permeability Controlled System developed by Amidon and
Leesman,29 comprising a core and a coating.?
http://www.ijpe.org/July2003/Article06Page02.html
?The development of oral controlled-release drug delivery systems has
been hindered by the fluctuation in gastric emptying time, the
variation in pH in different segments of the gastrointestinal (GI)
tract, and the difficulty of localizing an oral delivery system in a
selected region of the GI tract.?
http://www.aapspharmscitech.org/view.asp?art=pt020101&pdf=yes
?Coating materials are substances used to protect tablets from
moisture and prevent them from crumbling during manufacture, shipping
and storage. Coatings also mask unpleasant flavors or odors, making
tablets easier to swallow.Zein (often listed as "vegetable protein
coating") is a natural, corn-derived protein, and is a clear
film-coating agent. Brazil wax, a natural product derived from palm
trees, is also frequently used. Some companies actually use shellac in
their tablet coatings: it may be listed as "pharmaceutical glaze."
Shellac is insoluble in an acidic medium, such as the stomach. If your
client has compromised exocrine pancreatic function, resulting in
acidic conditions in the small intestine, a shellac-coated supplement
cannot be broken down or assimilated.
The coating or shell of capsules is usually made of gelatin, an animal
by-product. Strict vegetarians may not find these products suitable.
Vegetarian gel caps, derived from potato extract, are available but
are used by only a small number of companies. Additionally, clients
with hypochloridia or achloridia may be unable to break down the
protein gelatin of these capsules. Until their digestive capacity
improves, they may open the capsule and empty
its contents into food or drink.?
http://www.nutritional- solutions.net/Articles/BestSupplementsJeanneWallace.pdf
?These capsules are designed to dissolve and release the contents
within five minutes of entering the stomach.?
http://www.naturalhealthsupply.com/products/empty-gelatin-capsules.html
?gelatin caps dissolve rapidly (5-10 minutes) and completely in the stomach.?
http://members.verizon.net/~vze2r6qt/supplies/gelcaps.htm
?What happens to the capsule inside my body? - The water-soluble
gelatin shell dissolves in the stomach, releasing its' contents within
the first few minutes of swallowing.?
http://www.viable-herbal.com/capsules.htm
?The AUC for soft shell capsules in Drug A was 12.71, for Drug B was
12.55 and for Drug C was 12.96. Thus the AUCs for hard shell and soft
shell capsules whether stressed or unstressed were very similar and
their confidence intervals ranged within the acceptable limits of
80-125%. The mean Cmax for hard shell capsules- Drugs B and C were 11%
and 19% higher than the mean Cmax for Drug A and the confidence
interval for Drug A and C was between 104-132% and thus unacceptable.
The mean Cmax for soft shell capsules- Drugs B and C were both 11%
higher when compared to Drug A and the confidence interval for capsule
A and C was 102-128% and unacceptable. The Tlag in hard shell capsules
for Drug A, Drug B and Drug C were 0.08, 0.16 and 0.55 hours
respectively. The Tlag for soft shell capsules in Drug A, Drug B and
Drug C were 0.09, 0.15 and 0.51 hours respectively. Gender analysis
showed that there were no significant differences between males and
females when the pharmacokinetic parameters were compared in hard and
soft shell capsules. In conclusion, hard shell and soft shell capsules
may not affect the extent of absorption but may delay the rate of
absorption with increased levels of stressing. The Tlag time seemed to
increase with increase in stressing. These results also indicate that
the dissolution test to distinguish between stressed and unstressed
capsules may require revision to meet regulatory requirements.?
http://vm.cfsan.fda.gov/~frf/forum97/97B10.htm
?Enteric-coated. This special coating allows pills to pass undigested
thorough your stomach and be dissolved in your small intestine, which
helps reduce stomach irritation. Because the coating delays
absorption, it's not the best choice for quick relief, such as for a
headache.?
http://www.mayoclinic.com/health/pain-medications/PN00066
You may purchase this article for $30 USD
?To evaluate the gastric emptying time of pharmaceutical dosage forms
in a clinical setting, a relatively simple dual-radionuclide technique
was developed. Placebo tablets of six different combinations of shape
and size were labeled with indium-111 DTPA and enteric coated. Six
volunteers participated in a single-blind and crossover study. Tablets
were given in the morning on a fasting stomach with 6 oz of water
containing99mTc pertechnetate and continuously observed with a gamma
camera. A scintigraph was obtained each minute. The results suggested
that the size, shape, or volume of the tablet used in this study had
no significant effect in the rate of gastric emptying. The tablets
emptied erratically and unpredictably, depending upon their time of
arrival in the stomach in relation to the occurrence of interdigestive
myoelectric contractions. The method described is a relatively simple
and accurate technique to allow one to follow the gastric emptying of
tablets.?
http://www.springerlink.com/(qka4n045ouaoumq3agpzzk2f)/app/home/contribution.asp?referrer=parent&backto=issue,4,16;journal,160,480;linkingpublicationresults,1:401150,1
Cellulose Capsules
Cellulose (vegetable/plant) capsules are generally used as an enteric
capsule, meaning it is intended to dissolve and release contents in
the intestinal tract, and not the stomach.
?U.S. Pat. No. 4,774,230 (Tuttle et al) relates to the intestine
specific delivery of opioid antagonists including naloxone and
naltrexone for treating opioid induced and idiopathic constipation and
IBS. The drug is targeted to the intestine by virtue of an inactive
glucoronic acid derivative which is enzymatically cleaved by
glucoronidase, in the lower intestine and particularly the colon. The
glucoronic acid derivative may be in the form of capsules or tablets
for oral administration and may have enteric coatings such as
polyacrylates or cellulose acetate phthalates.?
http://www.pharmcast.com/Patents100/Yr2004/May2004/051104/6734188_Constipation051104.htm
?Capsules are either vegetable-based (veggie) or gelatin-based. Both
types will dissolve in your gut. Some people find that they get much
better results from veggie capsules if they wait about 20-30 minutes
to allow more time for the veggie capsules to dissolve. This has not
been an issue with gelatin capsules because they dissolve right away
at body temperature, whereas the veggie capsules may not.?
http://www.enzymestuff.com/basicsdosing.htm
?Cellulose Acetate Phthalate is used as an enteric coating on capsules
or tablets so they don't dissolve until they reach the small
intestine. Enteric coatings are selectively insoluble substances -
they won't dissolve in the acidic juices of the stomach, but they will
dissolve in the higher pH (above pH 5.5) of the small intestine.?
http://www.enerex.ca/articles/enteric_coating.htm
?When do capsules dissolve?
Capsules are water-soluble and are designed to dissolve in the
stomach. They are designed to start releasing their contents within
minutes after swallowing.?
http://www.qualicaps.com/faq.cfm
?1. If the gelling agent is added to the dispersing medium in a
haphazard manner, there is a tendency for the agent to "clump." The
outer molecules of the gelling agent contact the medium first and
hydrate forming a surface layer that is more difficult for the medium
to penetrate. The clumps will ultimately hydrate, but it will take
more time. A much more efficient manner is to sieve the agents onto
the surface of the medium a little at a time as the medium is
stirring. Using glycerin as a wetting agent will sometimes minimize
clump formation.
2. Some gelling agents are more soluble in cold water than in hot
water. Methylcellulose and poloxamers have better solubility in cold
water while bentonite, gelatin, and sodium carboxymethylcellulose are
more soluble in hot water. Carbomers, tragacanth, and alginic acid
gels are made with tepid water.
3. Some gelling agents (carbomers) require a "neutralizer" or a pH
adjusting chemical to create the gel after the gelling agent has been
wetted in the dispersing medium.
4. Most gelling agents require 24-48 hours to completely hydrate and
reach maximum viscosity and clarity.
5. Gelling agents are used in concentrations of 0.5% up to 10%
depending on the agent.
6. It is easier to add the active drug before the gel is formed if the
drug doesn't interfere with the gel formation.
7. Only Carbopol® 934P, methylcellulose, hydroxypropylmethylcellulose,
and sodium carboxymethylcellulose are recommended for oral
administration.?
http://pharmlabs.unc.edu/suspensions/text.htm
?I see products advertised that are labeled as "gelcaps"and
"softgels"; what are they? - ?Gelcaps? are basically tablets that are
coated with a layer of gelatin. ?Softgels? are composed of a thick
layer of gelatin, to which plasticizers have been added to maintain
flexibility and stability. The inner section of the softgel usually
contains a liquid form of the active ingredient.
What materials are used to manufacture hard gelatin capsules? - Hard
gelatin capsules are made of 86% bovine and/or pigs skin and 14%
purified water.
What materials are used to manufacture vegetable capsules? - Vegetable
capsules are made of 92% methyl cellulose and 8% purified water.
Hydroxypropyl methyl cellulose is a type of cotton fiber derived from
a soft wood pine tree that is specially cultivated in North America.
The unused portions of the trees are used in the pulp industry.
How are hard capsules manufactured? - The manufacturing process of
hard gelatin capsules begins by mixing and melting high quality
pharmaceutical grade gelatin, comprised of bovine, pig's skin or a
vegetable source. The capsule itself is formed with the use of precise
machinery that molds, dries, trims, joins and then packages the
capsules according to GMP processes (Good Manufacturing Practices).
Throughout this manufacturing process, capsules are inspected numerous
times by Quality Control experts, guaranteeing a stable, high
performing capsule.?
http://www.viable-herbal.com/singles/capsules.htm
? ?When drugs are being designed, scientists consider carefully where
in the digestive tract the drugs should be dissolved, ready to be
absorbed into the bloodstream. Scientists may need to ensure that a
drug:
- dissolves when it reaches a location with a specific pH
- reaches its destination without being broken down. It may have been
dissolved but it must still be chemically effective
- is released within an appropriate timeframe.
? The solubility of a drug can be affected by the nature of solvent,
the amount of agitation and the temperature.
? Soluble tablets will dissolve rapidly in water producing a liquid
solution. Liquids entering the digestive system are absorbed more
rapidly than solids. This is useful when fast-acting medication is
desirable.
? Some substances that are not very soluble in water can be dissolved
by the addition of other substances to produce a solution without
changing the therapeutic effect of the drug itself.
? Drugs that dissolve in acidic solutions will be absorbed through the
lining of the stomach and are then taken to other parts of the body by
the bloodstream. Those that dissolve in alkaline conditions will be
absorbed through the walls of the small intestine and are similarly
carried by the bloodstream.
? Medication may be designed especially to dissolve in the intestine
rather than the stomach.
? It is important for scientists to test medicines thoroughly because
the digestive tract can affect the drug and because the drugs may
cause damaging side effects. Some drugs are broken down in the
presence of acids and this may alter their effectiveness.
? Some drugs may cause damage to the lining of the stomach. For
example, some common drugs used in the treatment of arthritis are
enteric-coated to prevent their solution in the stomach, where they
may cause irritation or gastric upset. The coating is not dissolved in
the acidic environment of the stomach.
? Medication may be designed to dissolve over a period of time in
order to provide access to the drug without further ingestion.?
http://hsc.csu.edu.au/senior_science/core/life_chem/9_2_5/925net.html
Page 2 of this site outlines some dubious benefits of vegetable
capsules. I have been unable to substantiate this information
elsewhere, and it does contradict some of my other research. Other
more reliable sites indicate vegetable/cellulose capsules are slower
to dissolve.
Contains 1-2% toxic preservatives in the gelatin
Vegetable capsules are 100% preservative-free
? Temperature-sensitive; difficult to dissolve in cold temperatures
Vegetable capsules dissolve rapidly, regardless of food temperature
? Difficult to digest; its sticky nature inhibits the uptake of the
capsule contents; the more gelatin capsules you take, the poorer the
uptake
Vegetable capsules are easy to digest; promotes uptake of capsule
contents due to its fiber
? Animal source; carries the risk of ?mad cow? prion exposure
Vegetable capsules are from vegetable source?
http://www.healthline.cc/QNL%20Product%20Information/hyssop%20complex.pdf
Time Release Capsules:
?Elastomers, such as styrene-butadiene copolymer have been
suggested.22,23 Pulsatile release was achieved after lag times of 1 to
10 hours, depending on the thickness of the barrier layer and that of
semipermeable membrane,21 and a capsule designed for implantation can
deliver drug intermittently at intervals of 6 hours for 2 days.?
http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=250
Additional Studies and information:
===================================
http://www.rpsgb.org.uk/pdfs/bpc05sciabs213-232.pdf
http://www.engin.umich.edu/~cre/11chap/html/core.htm
http://www.lek.si/eng/research-development/pharmaceutical-technology/innovative-technologies/
An interesting, yet totally useless unscientific, uncontrolled
experiment, that completely excludes the effect of stomach acid and pH
on dissolution:
http://www.cruftbox.com/cruft/docs/dissolve.html
http://www.ijpc.com/_pdf/rapid.pdf
http://www.aapspharmscitech.org/view.asp?art=pt060356
I hope this answer is the one you were seeking. If not, please request
an Answer Clarification, before rating, and I will be happy to assist
you further, if possible.
Sincerely, Crabcakes
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