drug delivery
DESCRIPTION
IntroTRANSCRIPT
Pharmaceutics 5
Rassoul DinarvandProfessor of Pharmaceutics
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Drug levels in the blood with (a) traditional drug dosing and (b) controlled-delivery dosing
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Chemical engineering◦ Less soluble melts◦ Prodrugs◦ Targeting linkages (MAB)◦ Pegylation
Pharmaceutical engineering◦ Oil vehicles◦ Liposomes◦ Polymeric delivery◦ Cell based drug delivery
Particle engineering◦ Solid lipid particles◦ Dendrimers
Mechanical engineering◦ Mechanical pumps
• Large molecule composed of a number of sub-units- Natural e.g. alginates,
- synthetic e.g. poly(HMPA)
- Function governed by number and arrangement of constitutional repeat units e.g. –[A-]n, -[A-B-]n, -[A-A] n-[B-B] m , --A-A-B-A-B-B-A-
• How are they made?- Processing of natural products – alginates from seaweeds, celluloses
from plants
- Synthesis from chemical feedstocks – poly(olefins), nylons, poly(esters)
• How can they help?- Protection of therapeutic compound during passage through body, as
encapsulant or carrier.
- Mediator or activator of controlled release
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• Matrix (Monolithic) devices- films with the drug in a polymer matrix
- Easy to fabricate, typically by simple mixing of polymer and drug
- Example: Eudragit RS100 polymer, mixed with sorbitol and Flurbiprofen
• Polymer drug conjugates- Polymer attached to drug by (covalent) sacrificial linker
- Example: Paclitaxel-albumin conjugate in the market
Docetaxel-albumin conjugate under investigation
• Reservoir devices- Drug contained by the polymer
- Release is usually diffusion controlled (Fickian) i.e. J = -DC where J =flux, C = component of concentration across membrane of defined area, and is a differential vector operator
- Example: PharmazomeTM Theophylline release
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• Biodegradable polymers- Polymer degrades in vivo to release the drug
- Simple release mechanism, but difficult to obtain fine control over degradation
- Does not invoke an inflammatory or toxic response.
- Is metabolized in the body after fulfilling its purpose, leaving no trace
• Examples in use- Resomer (PLGA)
- Vicryl (PLGA)
• Common biodegradable polymers- Poly(lactide-co-glycolide) (PLGA)
- Poly(hydroxybutyrate-co valerate) (Biopol)
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Hydrogels• Three-dimensional, hydrophilic polymeric networks, swollen with
water
• Cross-linking between polymer chains determines swelling and gel flexibility
• Natural or synthetic derived – very large number of hydrogels have been produced
• Ionic (acidic, basic) or neutral dependent on desired application
• Inherently biocompatible – strongly hydrated
O
OOH
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O
HEMA EGDMA>95 parts <5 parts
polymeriseO
O
OH
OO
OO O
O
HO[] [
]
[] [
]Monomer (water-soluble) Cross-linker Hydrogel
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Mucoadhesives
• 2nd Major class of polymer drug delivery vehicles
- Similar in design features to hydrogels (sub-class)
- Ability to localise at mucus membrane via adhesive interactions
- Contain functional groups for binding to mucosal surfaces – primarily H-bonding
- Pendant chains for intimate contact and interdigitation with mucins
- Inherently biocompatible – strongly hydrated
O
OH
O
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Methacrylic acid(MAA)
Poly(ethyleneglycol)dimethacrylatePEGDMA
polymeriseO
HO
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OO O
OH
[] [
]
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]Adhesivegroups
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n
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Controlled release implies controlled release of drugs from polymer drug delivery systems (DDS)
Type of polymer◦ Non-degradable / Degradable
Type of Design
Reservoir Matrix
Release mechanisms◦ Diffusion / polymer degradation / combination
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Drug delivery from a typical matrix drug delivery system
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Drug delivery from a typical reservoir drug delivery system
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Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems
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Drug delivery from environmentally sensitive release systems.
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Molecular gates for the delivery of insulin triggered by the presence of glucose in the bloodstream
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Drug delivery from (a) bulk-eroding and (b) surface-eroding biodegradable systems
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Particulate systems◦ Nanoparticles
Nanocapsules Nanospheres
◦ Microparticles Microspheres Microcapsules
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Films Membranes Fibers Rods Beads Discs Cylinders
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Simultaneous drug loading and polymerisation/device fabrication
Drug loading after device fabrication◦ Drug uptake by polymeric device when immersed in
drug saturated solution◦ Mechanical drug loading
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DiffusionConcentration gradient in polymeric matrix
Chemical reactionPolymer biodegradation
Solvent effectRelease of soluble drugs in hydrogels
Mechanical releaseDrug release from mechanical devices such as
pumps
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Implants Injectables Transdermal Oral Nasal Ophthalmic Vaginal
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Solid tumor
Apply magnetic field to concentrate particles
Modulate field to release drug from particles
Inject NPs IV,NP will circulate through the blood stream
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