Pharmaceutics 5

Rassoul Dinarvand
Professor of Pharmaceutics

Pharmaceutics 5

Chemical engineering

Pharmaceutical engineering

Less soluble melts

Prodrugs
Targeting linkages (MAB)
Pegylation
Oil vehicles
Liposomes
Polymeric delivery
Cell based drug delivery

Particle engineering
Solid lipid particles
Dendrimers

Mechanical engineering
Mechanical pumps
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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

Reservoir devices
-

Drug contained by the polymer

Release is usually diffusion controlled (Fickian) i.e. J = -D C where J =flux, C =

component of concentration across membrane of defined area, and is a differential vector
operator

Example: PharmazomeTM Theophylline release

Polymer drug conjugates

-

Polymer attached to drug by (covalent) sacrificial linker

Example: Paclitaxel-albumin conjugate in the market

Docetaxel-albumin conjugate under investigation

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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

Common biodegradable polymers

-

Poly(lactide-co-glycolide) (PLGA)

Poly(hydroxybutyrate-co valerate) (Biopol)

Examples in use
-

Resomer (PLGA)

Vicryl (PLGA)

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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

] [

O
O

OH

O
O

HEMA

>95 parts

polymerise

O HO
O

O
O

EGDMA <5 parts

O
OH O

Monomer (water-soluble)

Cross-linker

Hydrogel

Pharmaceutics 5

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

] [

O
OH

O
n

Methacrylic acid
(MAA)

Poly(ethyleneglycol)
dimethacrylate
PEGDMA

polymerise

HO
OH

Adhesive
groups

O
O

[
Pharmaceutics 5

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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Diffusion
Concentration gradient in polymeric
matrix

Chemical reaction
Polymer biodegradation

Solvent effect
Release of soluble drugs in hydrogels

Mechanical release
Drug 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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