Pharmaceutical Technology

1. PHARMACEUTICAL TECHNOLOGY
POLYMERIZATION
PREPARED BY:
PHARM-D, 5TH YEAR PROFESSION

2. Group members
• HAFSA AHMED (151215)
• HIRA SAEED (151219)
• LARAIB SHAMSI (151227)
• MAHA KIRAN (151229)
• MAHAM FAYAZ (151230)
• MAHAM UROOJ (151232)

3. INTRODUCTION TO
INTERFACIAL
POLYMERIZATION

4. Polymerization is the process
of connecting these
monomers together and
creating large
macromolecules of different
sizes and shapes.
Polymerization is similar to
constructing a large building
out of the same type of Lego
blocks.
POLYMERIZATION

5. Microencapsulation is a process by which
individual particles of an active agent can
be stored within a shell, surrounded or
coated with a continuous film of polymeric
material to produce particles in the
micrometre to millimetre range, for
protection and/or later release.
TYPES OF POLYMERIZATION
1: In-situ polymerization
2: interfacial polymerization
MICROENCAPSULATION

6. In-situ polymerization is a chemical
encapsulation technique very similar to
interfacial polymerization. The distinguishing
characteristic of in-situ polymerization is that
no reactants are included in the core material.
All polymerization occurs in the continuous
phase, rather than on both sides of the
interface between the continuous phase and
the core material, as in interfacial
polymerization.
IN-SITU POLYMERIZATION

7. In-situ polymerization is similar to interfacial
polymerization, except there are no
reactive monomers in the organic phase, and all
polymerization takes place in the continuous
phase rather than in the interface of the droplets as in
interfacial polymerization.
PROCESS
(IN-SITU POLYMERIZATION)

8. Interfacial polymerization is a method
which involves the utilization of a
water-immiscible organic solvent to
emulsify an aqueous mixture
containing the enzyme and a
hydrophilic monomer.
INTERFACIAL
POLYMERIZATION

9.  This process uses two sets of reactive monomers.
These sets will react with each other, but must be
soluble in opposite solvent polarity to create the
capsule.
 The two monomers X and Y react at the interface to
form a polymer (XY)n The monomers could be
included in the same or on the opposite phase.
PROCESS
(INTERFACIAL POLYMERIZATION)

10. SUSTAINED RELEASE
DOSAGE FORM

11. ‘‘It is a drug delivery system
designed to achieve a prolong
therapeutic effect by
continously releasing after
administration of a single
dose.’’
 The therapeutic response for a
specific standard extended period
of time is usually 8-12 hours.
 Sustained release matrix tablet
was prepared by the polymers
blend with to get desirable drug
release profile.
 Examples are Acephar 200 SR,
Ricnac SR, B complex 100 SR
SUSTAINED RELEASE
DOSAGE FORM

12. ADVANTAGES DISADVANTAGES
 Reduction in frequency of
intakes.
Expensive
 Reduce side effects. Toxicity due to dose dumping.
Uniform release of drug over time Unpredictable and often poor
IVIVC.
Better patient compliance. High potential for first pass
clearance.
Need for additional patient
education and counselling.
ADVANTAGES & DISADVANTAGES
(SUSTAINED RELEASE DOSAGE FORM)

13. MATRIX TABLETS

14. Defined as the “oral solid dosage forms in
which the drug or active ingredient is
homogeneously dispersed throughout the
hydrophilic or hydrophobic matrices
which serves as release rate retardants.”
Matrix Tablets Type of controlled drug
delivery systems, which release the drug in
continuous manner.
It is an important tool for controlled and
sustained release dosage forms
MATRIX TABLETS

15. • Constitutes dosage form that
maintain constant drug levels in
blood or tissues.
• It attain zero order kinetics.
• Can be control.
CONTROLLED
DRUG
DELIVERY
SYSTEM
• Constitutes dosage form that
provide medication over
extended period of time.
• Generally donot attain zero
order release kinetics.
• May or may not be control.
SUSTAINED
DRUG
DELIVERY
SYSTEM
CONT….
(MATRIX TABLETS)

16. Easy to manufacture, Effective
Maintain therapeutic concentrations over
prolonged period
Reduce The Toxicity
ADVANTAGES
(MATRIX TABLETS)

17. The remaining matrix must be
removed after the drug has been
released
The released rate are affected by
various factors such as food & the
rate transit through gut
Release rate continuously diminishes
due to increase in diffusional
resistance
DISADVANTAGES
(MATRIX TABLETS)

18. The release of drug from polymer matrix
system is dependent upon the
physicochemical properties of both drug
and polymer as well as
It is also dependent on several biological
parameters.
FACTORS AFFECTING RATE DRUG
RELEASE FROM MATRIX SYSTEM

19. • Swelling property of polymer
• Drug solubility
• Dose size
• Stability
PHYSICOCHEMICAL
FACTORS
• Biological half life
• Absorption
• Metabolism
BIOLOGICAL
FACTORS
CONT…
(FACTORS AFFECTING RATE DRUG RELEASE FROM
MATRIX SYSTEM)

20. There are number of polymers which
may be used to formulate matrix tablets
depending on the physicochemical
properties of the drug substance to be
incorporated into matrix system and drug
release profile required.
POLYMERS USED IN
MATRIX TABLETS

21. POLYMERS EXAMPLES
1. Hydrogels Poly-hydroxyethyl
methacrylate (PHEMA)
2. Soluble Polymers Polyethylene glycol (PEG)
Polyvinyl alcohol (PVA)
3. Biodegradable Polymers Polyanhydrides
Polyorthoesters
4. Non-biodegradable Polymers Cellulose acetate (CA)
Ethyl cellulose (EC)
5. Natural Gums Xanthan guM
Gum arabic
6. Mucoadhesive Polymers Tragacanth
CLASSIFICATION
(POLYMERS USED IN MATRIX TABLETS)

22. CLASSIFICATION OF
MATRIX TABLET BASED
ON POROSITY OF MATRIX

23. Macro-porous System
Micro-porous System
Non-porous System
CLASSIFICATION

24. In such system the diffusion of drug occurs
through porous of matrix which of size
range 0.5-1mm.This pore sixe is longer
than diffussant molecular size.
MACRO POROUS SYSTEM

25. Diffusion in this type of system occur
through pores. For micro porous
system, pore size ranges from 50-
100A* which is slightly longer than
diffusion material
MICRO-POROUS SYSTEM

26. They have no pores and molecules, diffuses
through the network meshes, in this case only
the polymeric phase exist and no pore phase is
present.
NON-POROUS SYSTEM

27. CLASSIFICATION OF MATRIX
TABLETS

28. These matrix are prepared by lipid waxes and
related material drug release from such
matrix occur through both pore diffussion
and errosion
LIPID TYPE MATRIX

29. Easiest oral extended release system
The drug is mixed with an inert or hydrophobic
polymer and then compressed to a tablet
Fatty acid, fatty alcohol and waxes of natural
and synthetic origin such as carnuba wax, bees
wax, candella wax
Insoluble polymers include fine powders of
ammonio metha acrylate co-polymer (trade
name: eudrajit)
HYDROPHOBIC MATRIX

30. These consist of the polymer which comprised of
monomers linked to one another through functional
groups and have unstable linkage.
They are biologically degraded or eroded by enzymes
generated by surrounding living cells or by non
enzymatic process into oligomers and monomers that
can be excreted or metabolized
Examples:
1. Natural polymers: such as protein &
polysaccharide
2. Modified natural polymer:
3. Synthetic polymer: such as aliphatic polyester and
polysaccharide
BIODEGRABLE MATRIX

31.  The rate controlling materials are water soluble and swell
able matrix is a well mixed composite of one or more drugs
with gelling agent
 Non-ionic soluble cellulose ether: such as hydroxy propyl
methyl cellulose (HPMC) and hydroxy ethyl cellulose
(HEC)
 Non-ionic homopolymer of ethylenedioxide: such as
polyethylene oxide with a molecular weight of 100,000 to
8,00,0000
 Water soluble natural gums of polysaccharide of natural
origin: such as xanthum gum, alginate and locust bean gum
 Polyvinyl acetate and povidone mixture (kollidone)
HYDROPHILIC TYPE
MATRIX

32. HYDROPHILIC TYPE MATRIX

33. INTRODUCTION TO
RESERVOIR BASED DRUG
DELIVERY SYSTEM

34.  The reservoir-based system is one of the most common controlled
drug delivery systems.
 In these systems, a drug core is surrounded by a polymer film.
 The drug release rate is controlled by:
 The properties of the polymer (e.g, polymer composition and
molecular weight).
 The thickness of the coating.
 The physicochemical properties of
the enclosed drug. Such as:
 Solubility.
 Drug particle size.
 Molecular weight
RESERVOIR BASED DRUG
DELIVERY SYSTEM

35. Reservoir-based systems are most beneficial for
one of the following two applications:
1. A mid-/long-term administration of a medication
that is localized to a specific region (i.e., Organ,
body cavity, etc.).
This is usually done if the area being targeted is
difficult to reach via systemic administration
(i.e., Eye, ear) and/or the drugs administered are
toxic and may require a long-term course of
dosing (i.e., Cancer treatments).
BENEFITS RESERVOIR SYSTEM

36. 2. A drug depot for long-
term systemic
administration.
This is generally
administered as an
intramuscular or
subcutaneous injection
or implantation. Based
on the morphology, the
reservoir-based system
can be classified as the
following categories.
CONT….
(BENEFITS RESERVOIR SYSTEM)

37. CLASSES OF RESERVOIR-BASED
POLYMER DRUG DELIVERY SYSTEMS.

38. DEVELOPMENTAL OF
RESERVOIR SYSTEMS

39. POLYMERS FOR RESERVOIR-BASED
CONTROLLED RELEASE SYSTEMS
Polymers used in the drug delivery systems can be classified into the
following categories:
Diffusion controlled (non biodegradable).
Chemically controlled (biodegradable).
Externally triggered systems (smart polymers responded to ph,
temperature, etc.).
NON- BIODEGRADABLE POLYMERS
The polymers that are commonly used in diffusion-controlled systems
are usually nonbiodegradable.
In these systems, because the polymers are not biodegradable, there is
usually no initial burst release, and the release kinetics are determined by
the thickness and permeability of the polymer, the release area, and the
solubility of the drug.
The non biodegradable polymers that have been used most are silicone,
cross-linked pva, and eva.

40. BIODEGRADABLEPOLYMERS
(POLYMERS FOR RESERVOIR-BASED CONTROLLED RELEASE SYSTEMS)
BIODEGRADABLE POLYMERS
Biodegradable polymers find widespread use in the drug delivery
industry.
There are two types of biodegradable polymers:
 Natural polymers
Synthetic polymers.
Collagen and gelatin are the two natural biodegradable polymers that
have been deployed most for drug delivery systems

41. MECHANISM OF DRUG
RELEASE FROM
ORAL DRUG DELIVERY
SYSTEM

42. Diffusion process shows the movement of drug molecules
from a region of a higher concentration to one of lower
concentration
 In this system, a water insoluble polymeric material
covers a core of drug. Drug will partition into the
membrane and exchange with the fluid surrounding the
particle or tablet.
 Additional drug will enter the polymer, diffuse to the
periphery and exchange with the surrounding media. The
drug release takes place by diffusion mechanism.
TYPES OF DIFFUSION SYSTEM
 DIFFUSION MATRIX SYSTEM
 DIFFUSION RESERVOIR SYSTEM
DIFFUSION SYSTEM

43. The matrix system is defined as a well-mixed
composite of one or more drugs with gelling agent
i.e. hydrophilic polymers.
Also called as monolithic controlled devices
Matrix systems are widely used for sustaining the
release rate. It is the release system which prolongs
and controls the release of the drug that is
dissolved or dispersed
The rate of release of dissolution of the drug within
the matrix need to be higher than the rate at which
it is released
Drug release determined by dissolution rate of
polymers
DIFFUSION MATRIX
SYSTEM

44. DIFFUSION MATRIX
SYSTEM

45.  Also called as laminated matrix device
 In this system, a water insoluble polymeric material
covers content in coating, thickness of coating & hardness
of micro-capsules control the release of the drug
 Hollow system containing an inner core surrounded in
water insoluble membrane.
 Polymer can be applied by coating or micro
encapsulation.
 Rate controlling mechanism - partitioning into membrane
with subsequent release into surrounding fluid by
diffusion.
Rate controlling steps :
Polymeric content in coating, thickness of coating ,
hardness of microcapsule.
DIFFUSION RESERVIOR
SYSTEM

46. CONT….
(DIFFUSION RESERVIOR SYSTEM)

47.  Drug with a slow dissolution rate is inherently sustained and for
those drugs with high water solubility, one can decrease
dissolution through appropriate salt or derivative formation
 . These systems are most commonly employed in the production
of enteric coated dosage forms. To protect the stomach from the
effects of drugs such as Aspirin, a coating that dissolves in
natural or alkaline media is used. This inhibits release of drug
from the dosage form until it reaches the higher pH of the
intestine.
 In most cases, enteric coated dosage forms are not truly
sustaining in nature, but serve as a useful function in directing
release of the drug to a special site. The same approach can be
employed for compounds that are degraded by the harsh
conditions found in the gastric region.
DISSOLUTION SYSTEM

48. Two classes:
Encapsulation/Reservoir
dissolution control
Matrix dissolution control
CONT…..
(DISSOLUTION SYSTEM)

49.  In this system drug is coated with a
given thickness coating, which is slowly
dissolved in the contents of
gastrointestinal tract by alternating layers
of drug with the rate controlling coats
 systems involve coating of individual
particles of drug with a slow dissolving
material & the coated particles can be
compressed directly into tablets or
placed in capsules
 It can also be used to administered beads
as a group, their release occurs in a
progressive manner.
ENCAPSULATION/RESERVOIR
DISSOLUTION CONTROL

50. CONT….
(ENCAPSULATION/RESERVOIR DISSOLUTION
CONTROL)

51. In matrix systems the drug is homogeneously
dispersed throughout a rate controlling medium.
They employ waxes such as beeswax, carnauba
wax, hydrogenated castor oil etc which control
drug dissolution by controlling the rate of
dissolution fluid penetration into the matrix by
altering the porosity of tablet, decreasing its
wettability or by itself getting dissolved at a slower
rate.
The wax embedded drug is generally prepared by
dispersing the drug in molten wax and solidifying
and granulating the same
MATRIX DISSOLUTION
CONTROL SYSTEM

52. CONT….
(MATRIX DISSOLUTION CONTROL SYSTEM)

53. The drug core is enclosed in a
partially soluble membrane.
Pores are created due to
dissolution of parts of
membrane.
It permits entry of aqueous
medium into core & drug
dissolution.
Diffusion of dissolved drug
out of system.
Ex- Ethyl cellulose & PVP
mixture dissolves in water &
create pores of insoluble ethyl
cellulose membrane.
DISSOLUTION & DIFFUSION
CONTROLLED RELEASE
SYSTEM

54. MECHANISM of DRUG RELEASE
FROM
ORAL DRUG DELIVERY SYSTEM

55. OSMOTICSYSTEM
In which drug may be osmotically active or
drug may be combined with osmotically active
salts like NaCl

56. ELECTRICALLY STIMULATED
RELEASE DEVICE
A scientist “yuk” prepared matrix device
using polyelectrolyte gel which swell
when an electrical stimulus was applied
causing a change in pH,the release could
be modulated by the current giving a
pulsatile release profile.

57. HYDROGELS
In which three dimensional structures of
hydrophilic polymers having chemical
and physical cross links provide a
network structure to hydrogels.
These are insoluble due to network
structure and provide desirable protection
of liable drugs, proteins and peptides.

58. ION EXCHANGE RESIN
In these systems,
ionisable drug is absorbed
on ion-exchange resins
granules then granules are
coated with water
permeable polymers using
spray dryer technique.

59. CHEMICALLY CONTROLLED
RELEASE SYSTEMS
Chemically controlled release systems are the
systems that change their chemical structure,
when exposed to biological fluid
Mostly, biodegradable polymers are designed to
degrade as a result of hydrolysis of the polymer
chains into biologically safe and progressively
smaller moieties.
It is of two types and they are:
A)Erodible systems
B)Pendent chain system

60. A)ERODIBLE SYSTEMS
 In erodible systems, the mechanism
of drug release occurs by erosion.
 Erosion may be two types
 Bulk erosion:- polymer degradation
may occur through bulk hydrolysis.
 Surface erosion:- Polymers like
polyorthoesters and polyanhydrides
etc occurs degradation only at the
surface of the polymer.

61. B)PENDENT CHAIN
SYSTEM
• Pendent chain systems consists of linear homo or
copolymers with the drug attached to the
backbone chains.
• The drug is released from the polymer by
hydrolysis or enzymatic degradation of the
linkages.
• Zero order can be obtained and the cleavage of
the drug is the rate controlling mechanism.
Example for polymers used in pendent chain
systems like n-(2-hydroxy
propyl)methacrylamide etc.