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There are many circumstances in which it is desirable to deliver drugs to
an individual at a controlled rate, so as to extend the action of the drug
over a convenient time span. The most common examples of this are
decongestants and allergy medicines, in which it is very convenient for
individuals to take a single pill every twelve hours, as opposed to taking a
pill every two to four hours. Another example is the use of pain
relievers. Timed release formulations of pain medication allow a convenient
way for sufferers of chronic pain, such as arthritis or back pain, to lead
more normal lives without the necessity of taking pills on a frequent basis.
Probably the most common method of releasing drugs in a controlled fashion
utilizes coatings. Generally, with this method the drug is coated with
polymers or inorganic materials that have varying resistance to breakdown by
the body’s digestive system. Upon biodegradation of these coatings, the drug
is gradually released to the body. Release rates can be controlled by
varying the thickness of the coating, use of multiple coatings, utilization
of multiple layering of drug and coatings, dissolution rates, and/or pH
responsiveness of the coating. Problems with this approach (beside the
sizable intellectual property considerations) include the fact that the rate
of release generally occurs most rapidly where you don’t want it to (the
stomach) and the ease with which the timed-release nature of the technology
can be circumvented (purposefully or not). In the case of common drugs of
abuse, such as opiates and other alkaloids, simply grinding or chewing the
pill up thoroughly before it is swallowed or dissolving the pill in acid and
the extracting the drug will by-pass current controlled release protections
and may result in overdose, addiction, or ineffectiveness of the prescribed
medication.
Researchers in the University of Wyoming’s Department of Chemistry have
developed and filed a patent application on a novel method for the
controlled release of drugs that addresses these problems. With this
technology, the drug is attached to a polymer by means of a covalent bond
that is not readily cleaved by the ordinary conditions found in the
digestive tract (mouth, stomach, intestines). While attached to this
polymer, the drug is not bioavailable; that is, it cannot be utilized by the
body, and is effectively inert, having no physiological action. Since it is
chemically attached to the polymer, the use of any conventional physical
means to break down the drug-delivery molecule (e.g., grinding, chewing,
heating, extracting with aqueous or organic solvents) will have no effect in
releasing the drug. When the drug delivery composition reaches the stomach,
an acid-mediated unmasking reaction occurs that changes an important
functional group (the triggering group) from its masked, inactive form, into
its active form. In its active form, this triggering group is capable of
rupturing the covalent bond by which the drug is attached to the polymer in
a controllable fashion, thereby releasing the drug to the body in its
physiologically-active form. This rupture (the release reaction) may occur
by way of a unimolecular reaction or may occur by means of an intramolecular
reaction involving the triggering functional group itself.
The rate at which drugs are released may be controlled by the rate of the
unmasking reaction, by the rate of the release reaction, or by a combination
of these rates. In most circumstances it will be desirable to have a rapid
unmasking reaction that is followed by a slower release reaction, the rate
of which can be varied in a predictable fashion. This is desirable because
it allows for the drug delivery composition to be “unmasked” as soon as it
reaches the stomach where pH conditions of about 1-3 prevail, and for the
actual drug delivery to take place in the environment of the intestinal
tract, where adsorption is more effective.
If you would like to learn more
about this technology and how your company may apply it in commercial
situations, please contact the director of the University of Wyoming
Research Products Center,
Davona Douglass.
We would be pleased to further discuss details of the
invention. The disclosure is also available from the patent office in
document WO2003051113 A1.
Research Products Center
Dept. 3672
1000 E. University Ave.
Laramie, WY 82071
(307)766-2520
Fax: (307) 766-2530
e-mail: WyomingInvents@uwyo.edu