CONTROLLED DRUG RELEASE

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CONTROLLED DRUG RELEASE

• Department of Chemical Engineering, University Of
  Waterloo, Waterloo, Ontario
• Chemical Engineering Concepts 1
• Professor Mario Ioannidis
• The University of Waterloos Web Page
• Mike Di Fabio, 20060432
• Claire Allen, 20060497
• Andrea Lekawski, 20064395
• Christopher Takacs, 20082405
• K section -03

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WHAT IS CONTROLLED DRUG RELEASE

• This site contains information about the
  history of controlled drug release, its different
  applications, mainly intravenous, oral, and
  transdermal, and the future of controlled drug
  release. The underlying theory behind controlled
  drug release is to maintain a level concentration
  of medicine in the body that will allow more
  effective treatment.
• The goal of controlled drug release is to
  minimise the use of invasive instruments in
  patient care. This concept is still relatively
  new and there is a lot of excitement surrounding
  its possible applications.

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WHERE IT ALL STARTED...

• 1950s- Wursters Process was developed at the
  University of Wisconsin. When the idea to
  control the release first came about, they needed
  a way to encapsulate the drugs. The next slide
  shows a picture of this machine. The machine
  uses a fluid bed and a drying devices to surround
  particles. It was the first machine invented for
  this purpose. The main idea behind this is
  microencapsulation.
• 1953- Coavercation. This allowed drugs to be
  encapsuled when in the liquid form.
• 1956-1966 Over 50 patents were filed for
  different types of microencapsulation.
• 1970s- Implants were developed.
• 1980s- Transdermals were created.
• 2001 And the future- focus on site directed
  delivery systems.

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INTRAVENOUS DRUG DELIVERY

• Most people will encounter some form of
  intravenous drug delivery during the course of
  their lifetime. More often than not, it is
  considered an unpleasant intrusion. What many
  people do not realize though, is that the
  alternative could be much worse.
• Because the human body has the ability to
  completely circulate blood throughout the system
  within one minute, injecting medicine directly
  into the blood stream distributes medicines
  throughout the body quickly. Combined with
  advanced control methods, the performance of
  drugs can be increased by regulating the flow
  rate into the body by maintaining a specific
  concentration or delivering drugs at regular
  intervals.
• There are three main types of intravenous
  infusion therapy
• i) Gravity Flow
• ii) Mechanical Pump
• iii) Syringe Pump

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INTRAVENOUS DRUG DELIVERY

• Gravity Flow Intravenous Therapy delivers
  drugs, contained in a resevoir above the patient,
  by allowing gravity to force the drugs contained
  in the fluid to flow into the circulatory system.
  The hydrostatic pressure caused by the elevation
  creates a greater pressure into the venous blood
  stream. As the arterial system has a relatively
  higher pressure, a gravity delivered drug
  introduced via the arteries is not possible.
• Similar to gravity fed systems, Mechanical
  pumps drive medicines into the body via a
  catheter inserted into a vein. Using a pipe
  allows more control over flow rate. Minor
  adjustments can also be made according to how the
  patient is responding to the medicine.
  Additionally, it allows doses to be administered
  at regular intervals if a steady concentration is
  undesirable.
• Syringe pumps have been vitally important in
  delivering drugs to the body throughout the last
  century. New developments have allowed syringes
  to better control the delivery of drugs to
  localized areas (ie. Delivering Novacane before
  extracting a tooth)

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Oral Release Systems

• Delivery Rates
• There are four different rates through which the
  drug can be delivered to the body sustained
  release, modified release, pulsatic release, and
  chrono release (i.e. chronotherapy).
• Sustained Release (Fig. A)
• The drug is released in the body at a specific
  rate over an extended period of time, allowing
• optimal therapeutic effects. This is a very safe
  process that allows the patient to reduce the
• number of doses.
• Modified Release (Fig. B)
• A relatively large portion of the drug is
  released immediately to provide immediate
  effects.
• The remainder is released in a sustained fashion.
  This method of release is applicable to
• pain relief medication, since the patient will
  receive immediate and continuous comfort .
• Pulsatic Release (Fig. C)
• Designated amounts of the drug are released
  according to a schedule defined by time
• delays. This method of drug release is very
  useful for certain cardiovascular compounds to
• optimize the drugs effects.
• Chrono Release (Fig. D)

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These graphs represent the amount of drug
delivered to the body over a period of time for
each of the delivery rates.
Oral Release Systems
Sustained Release (Fig A)
Modified Release (Fig B)
Pulsatic Release (Fig C)
Chrono Release (Fig D)
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Oral Release Systems

• Delivery Methods
• Diffusion
• The diffusion system is either composed of a
  polymer membrane encapsulating the drug, or a
  polymer matrix in which the drug is suspended.
  Water diffuses through the polymer and dissolves
  the drug, which then diffuses out of the polymer.
  The rate of release of the membrane system is
  time dependent, while the matrix system is
  dependent on the concentration of drug present.
• Solvent-Activated Release
• This system is composed of a semi-permeable
  membrane with a small, laser drilled hole.
  Inside is an osmotic agent, either the drug
  itself or a salt, that causes water to enter the
  system. The resulting increase in pressure
  forces the drug to leave the system through the
  hole. The rate of release for this system is
  constant.
• Degradation
• The degradation packaging system involves either
  water-soluble polymers made insoluble through
  cross linking, water-insoluble polymers made
  soluble by hydrolysis or ionization of side
  groups, or water-insoluble polymers that are
  cleaved into soluble monomers. In all of these
  types, the main theory behind the system is that
  as they are exposed to water, the polymers break
  up, releasing the drug. The rate of release for
  this system is unpredictable, and entire dose
  dumping can occur.

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TRANSDERMAL DRUG RELEASE 1

• Transdermal drug release is a system that uses a
  small patch that is placed on the skin.
• The skin then absorbs the liquid within the
  patch. This concept was first discovered at the
  turn of the century, when dimethyl sulfoxide was
  found to reach the systemic circulation when
  placed on the skin. Since that time there have
  been several advances in the field of transdermal
  controlled drug release.
• There are two fundamental types of transdermal
  drug release (i) skin-controlled device, this
  type relies on the skin to control the rate at
  which the drug is absorbed (ii)
  system-controlled device, this type relies on the
  system to control the rate at which the drug
  enters the body. (1) These two different designs
  correspond to two different dosing systems, (i)
  reservoir system and (ii) monolithic system.
• The reservoir system is made up of four layers a
  water-resistant backing layer, the drug
  reservoir, the rate controlling membrane, and the
  adhesive layer which directly contacts the skin.
  As this system releases a constant amount of the
  drug over a specified amount of time, the rate of
  delivery must always be less than what the skin
  can absorb in that time period.

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TRANSDERMAL DRUG RELEASE 2

• The monolithic design has only three layers a
  water-resistant backing, a polymer matrix
  containing the drug and the adhesive layer that
  comes into direct contact with the skin. For this
  system, the skin controls the rate of absorption
  therefore the rate of delivery must always be at
  exactly what the skin can absorb. As this level
  decreases, the rate of delivery decreases as
  well.
• The advantages of transdermal drug release
  systems are
• Avoids drug interactions
• Substitute for oral drugs
• Several day therapy with a single application
  
• The disadvantages of transdermal drug release
  systems are
• Cannot be used with all drugs
• Limited time that a patch can remain on the skin
• Skin sensitivities

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RELATED DIAGRAMS
Fig. 2 Monolith
Fig. 1 Wursters Process
Fig. 3 Membrane
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THE FUTURE

• This industry is just starting to grow, and many
  changes are taking place.
• Researchers are trying to provide more control
  over the release of the drug, improve the
  efficency, safety, and convience, and to decrease
  side effects. The possibilities for controlled
  drug release are quite broad.
• So much research is being done that it is hard
  to pin point what will happen in the future. To
  see what direction some people are heading, look
  at theJournal of controlled Drug Release
  (http//www.elsevier.nl/locate/inca/502690)
  research is also being done by many societies,
  such as the Controlled Release Society, and the
  Japanesse Society of Drug Delievery Systems
  (http//www.engr.umbc.edu/chaubal/com.html).
  Research being done by pharmacies can also be
  found on this site.
• There are hurdles that must be overcome in order
  to make controlled drug release a more effective
  tool, but researchers around the world are trying
  to find solutions to problems that still persist
  today.

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REFERENCES

• Ansel, HC. 1995. Pharmaceutical Dosage Forms
  and Drug Delivery Systems. Malvern, PA Williams
  and Wilkins. Available Online
  http//www.cop.ufl.edu/safezone/prokai/pha5110/tdd
  s.htm
• Bronzino, Joseph D. 1995. Parenteral Infusion
  Devices. In The Biomedical Engineering Handbook,
  ed Butterfield, Robert D (1311-1321). Boca
  Raton, Florida CRC Press Inc.
• Eurand Corporation. Customised Release.Available
  online http//www.eurand.com/wt/tert.php3?page_na
  mecustomized_rls
• Maria Jose' Alonso, Dept. Pharmaceutical
  Technology. University of Santiago de Compostela,
  Spain. Controlled Release Of Peptides And
  Antigens From Biodegradable Polymer
  Microspheres. Available online
  http//www.medfarm.unito.it/pharmaco/itcrs/erasmus
  /erasm20.html
• Ms. Tesheia Johnson, PhD at Yale University.
  Available online http//www5.bae.ncsu.edu/bae/res
  earch/blanchard/www/465/textbook/otherprojects/dru
  gDeliver_97/intro.htm

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REFERENCES

• Segal, Marian. October 1991. Patches, Pumps,
  and Timed Release new ways to deliver drugs.
  Available at http//www.fda.gov/bbs/topics/CONSUM
  ER/CON000112.html
• Thrash, T. 1995. Controlled-Release Drug
  Delivery Systems Mechanisms of
  Intestinal-Specific Polymeric Degradation.
  Available online http//www.denison.edu/chem/DCS/
  journal/thrashv1n1.shtml
• Wendy Chan. 1999/2000. Nicotine Patches What
  quitters use to win. Journal of young
  Investigators Undergraduate Science Journal.
  Available online http//jyi.org/issues/issue3/fea
  tures/chan.html.
• Figure 1 Available Online http//www.bae.ncsu.
  edu/bae/research/blanchard/www/465/textbook/otherp
  rojects/drugDeliver_97/wurster.html
• Figure 2 and 3. Ansel, HC. and Allen, Lv Jr.
  1999. Pharmaceutical Dosage Forms and Drug
  Delivery Systems. Seventh Edition.
  Philadelphia, PA Lippincott Williams and
  Wilkins. Available online http//www.bae.ncsu.e
  du/bae/research/blanchard/www/465/textbook/otherpr
  ojects/drugDeliver_97/