SMART PHARMACEUTICALS: HYDROGELS IN DRUG DELIVERY

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SMART PHARMACEUTICALSHYDROGELS IN DRUG DELIVERY
Tony Lowman Department of Chemical
Engineering Drexel University email
alowman_at_cbis.ece.drexel.edu
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GOALS OF CONTROLELD RELEASE SYSTEMS
Profile of conventional drug delivery system
DOSE 1
DOSE 2
Toxicity
DRUG PLASMA LEVEL
Therapeutic
TIME

• LIMITATIONS
• Multiple administrations necessary to maintain
  drug in
• therapeutic amounts in the blood stream
• Plasma concentration may exceed the toxicity
  level
• Side effects could be severe
• Increased cost of pharmaceutics

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GOALS OF CONTROLELD RELEASE SYSTEMS
Profile of ideal controlled release system

• Maximize therapeutic efficacy of drug
• Reduced costs due to optimal administration
• Reduction in side effects

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Hydrogels

• Hydrophilic, insoluble polymer structures
• Insoluble due to chemical or physical crosslinks
• Imbibe large amounts of water (or physiological
  fluids)
• Highly biocompatible!!!!

Drug delivery Tissue engineering scaffolds Wound
healing devices Vascular grafts Orthopedic
implants.
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Hydrogels

• Numerous classifications
• Wide range of properties
• Numerous applications in drug delivery

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Structural Parameters
? , Mc
rh
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Classifications

• 1. Nature of gel
• Neutral
• Ionic
• Responsive

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Classifications

• 2. Types of polymers
• homopolymers
• Copolymers
• Interpenetrating networks
• Physical structure
• amorphous
• semi-crystalline
• H-bonded structures
• colloidal aggregates

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Classifications

• Morphological
• Non-porous 10-100 Å
• Microporous 100-1000 Å
• Macroporous 0.1-10 mm

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Classifications

• Release mechanism
• Diffusion controlled release system
• Swelling controlled release systems
• (BIO) erodible/degradable systems
• Pendant chain systems
• Responsive systems
• SIGNIFICANT OVERLAP EXIST!!!!

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Diffusion Controlled Release Systems
Reservoir system
Matrix system
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Diffusion in Polymer Networks
? , Me
rh
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Diffusion Controlled Release Systems
(1)
(2)
Short time approximation (80 release)
(3)
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Swelling Controlled Release Systems
W, water G, swollen gel D, drug P, glassy
polymer u, front velocity
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Diffusion vs. SwellingControlled?
(1)
(2)
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(BIO?)Degradable/Erodible Systems
Can use stimulus to degrade/erode/dissolve
polymer
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Pendant Chain Systems
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Responsive systems
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Responsive systemspH-responsive
UPPER SMALL INTESTINE
STOMACH
pH increase
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Experimental Techniques
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Network Structural Analysis
(1)
(2)
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Determination of Drug Diffusion Coefficients
Membrane permeability experiments Ficks 1st
Law
(1)
(2)
(3)
(4)
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Experimental Determination of Drug Diffusion
Coefficients
Membrane permeability experiments
Permeability of vitamin B12 through PEG
hydrogels.
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Experimental Determination of Drug Diffusion
Coefficients
Release experiments Geometric constraints
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Experimental Determination of Drug Diffusion
Coefficients
Dissolution experiments
k 4D1/2/(? 1/2 ?)
Release of vitamin B12 from PEG hydrogels.
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For more information

• A.M. Lowman and N.A. Peppas, "Hydrogels" in E.
  Mathiowitz, ed., Encyclopedia of Controlled Drug
  Delivery, Wiley, New York, 1999, pp. 397-418.
•  
• N. Peppas, Hydrogels in Medicine and Pharmacy,
  CRS Press, Boca Raton, 1986.