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POLYMERS IN SOLID STATE AND
PHARMACEUTICAL APPLICATIONS OF POLYMERS
BY
M. PRIYANKA
M. PHARMACY
SCHOOL OF PHARMACEUTICAL SCIENCES AND TECHNOLOGIES, JNTUK
CONTENTS
POLYMERS IN SOLID STATE
• Solid state properties
• Mechanical properties
• Thermodynamics of fusion & crystallization
• Heat of crystallization & fusion
PHARMACEUTICAL APPLICATIONS OF POLYMERS
• Applications of polymers in formulation of controlled drug delivery system
• Other applications
• Recent advances in the use of polymers for drug delivery systems
2
POLYMERS IN SOLID STATE
• The use of solid polymers depends on their mechanical, permeability, thermal &
optical properties which are governed by their chemical nature & morphological
characteristics.
A. SOLID STATE PROPERTIES:
a) THE AMORPHOUS STATE:
Randomly coiled interpenetrating chains
Not all volume is occupied: free volume concept
Diffusion of small molecules
Segmental & chain mobility strongly dependent on temperature & free volume
Entanglements at sufficiently high molecular [email protected]
3
b) SEMI-CRYSTALLINE STATE:
Partly ordered & partly folded state
c) CRYSTALLINE STATE:
Stiffness & brittleness
Fracture strength & elongation at break
Solubility
Permeation of gases & water sorption
B. MECHANICAL PROPERTIES:
Solids can be deformed by tension, bending, shear, torsion & compression. The
most widely used tool is tension. The following discussion is limited to tension.
Stress is the applied force F, per unit area of cross section A. stress in tension is
called tensile stress . The mostly used units of stress are lb/𝑖𝑛2 or psi, dyne/cm2. The
effect of stress is deformation or strain. Strain intension is called elongation∈. It is the
increase in length ∆𝐿 = 𝐿 − 𝐿𝜊 relative to the original length L0
∈=𝐿 − 𝐿0𝐿0
= ∆𝐿/𝐿0
5
• L is the length under a given tensile stress. Ideal or elastic solids are deformed
when subjected to stress. But regain their original shape & dimension when the
stress is released. According to Hooke’s law, the stress is directly proportional to
the strain.
𝐹
𝐴=𝐸 𝐿 − 𝐿𝜊
𝐿𝜊
• The proportionally constant E called Young’s modules or modules of elasticity is a
measure of hardness, stiffness or rigidity of a solid.
𝐸 = Δ𝜎/Δ ∈
a) INTER CHAIN COHESIVE FORCES :
The forces responsible for the mechanical strength of packaging films & plastic
containers are the secondary valence forces between adjacent polymer chains.
The most commercial films, fibres, plastics & elastomers are all in the range
of 70-85 K.cal/mole. Cohesive energies b/w 1.0 & 2.0K.cal/mole are the lowest.
The solid polymers of this category are elastomers with the lowest mechanical
strength plastics are stronger. Their cohesive energies range from 2-5 K.cal/mole &
involve dipole-dipole attraction in addition to dispersion forces. The highest inter
chain attraction greater than 5 K.cal/mole produces materials with the highest
strength, suitable for use as films & fibers.
b) CRYSTALLINITY:
• Maximum inter chain attraction resulting in greatest mechanical strength; Thus, to
be mechanically strong, A polymer should highly crystalline. Conversely, a weaker
& soften polymer for use as elastomer can be obtained by preventing
crystallization by random co-polymerization. Short chain branching disrupts the
crystallinity of solid polymers & weakens them mechanically.
c) MORPHOLOGY
• Crystalline domains are called crystallites. They alternate with more disordered
amorphous regions. Single polymer chain often run through several contiguous
crystallites & amorphous regions. Crystallization proceeds as these nuclei grow
into crystallites until all the solvent has evaporated or all the malt has solidified.
d) SPHERULITES:
• Crystallization in synthetic polymers often produces polycrystalline aggregates
called spherulites. These are spherical, radially symmetric arrays of fibrillary
crystallites ranging in diameter from less than 1 to several mm.
• Slow cooling of molten plastics produces fewer but large spherulites. The addition
of nucleating agents produces more & small spherulites.
C. THERMODYNAMICS OF FUSION & CRYSTALLIZATION:
• A binary system solvent-polymer is now applied to the one component system
consisting of the polymer aloe, to describe the reversible process.
Liquid amorphous polymer
Solid crystalline polymer
Solidification &
Crystallization
Melting or
Fusion
Gf = Hf - [email protected] 11
D. HEAT OF CRYSTALLIZATION & FUSION:
• The latent heat of crystallization or solidification HCR is negative because the
process is exothermic. When the polymer is solid, the chains arrange themselves
into an orderly lattice heat of fusion HF represents the energy that must be
supplied to break large fraction of the secondary valence forces between
neighbouring chains as the polymer melts. High density poly ethylene has a heat
of crystallization of -1850 cal/mole & heat of fusion of +1850 cal/mole. The
corresponding values for low density polyethylene are about one half of these
because of its lower crystallinity.
E. ANALYTICAL TECHNIQUES FOR POLYMER ANALYSIS:
Electron microscopy
Gel permeation chromatography with multiple detection
NMR (nuclear magnetic resonance)
Pyrolysis GC
Thermal analysis, TGA & DSC
X-ray diffraction techniques
PHARMACEUTICAL APPLICATIONS OF POLYMERS
• Polymers plays an important role in pharmaceuticals. In the 20th revision of the US
pharmacopoeia, polymers have officially entered into the world of pharmacy. As
the polymers have different kind of applications, they have been using in various
dosage forms as
Binders
Suspending agents
Emulsifying agents
Drug release modifiers
Disintegrating agents
Coating materials
14
A. APPLICATIONS OF POLYMERS IN FORMULATION OF CONTROLLED DRUG DELIVERY SYSTEM
• Oral drug delivery system
• Transdermal drug delivery system
• Ocular drug delivery system
1. ORAL DRUG DELIVERY SYSTEM:
Here, the drug gets released at controlled rate when administered orally. For that
several mechanisms are involved.
a) Osmotic pressure controlled GI delivery system
b) Gel diffusion controlled GI delivery system
c) Muco-adhesive GI delivery system
a) OSMOTIC PRESSURE CONTROLLED GI DELIVERY SYSTEM:
It is a controlled release oral drug delivery system in the form of a tablet. The
tablet has a rigid water permeable jacket. As the tablet posses through the body,
the osmotic pressure of water entering the tablet pushes the active drug through
semi-permeable membrane. In this system, semi-permeable membrane plays a key
role. Release of drug depends on it. Semi-permeable membrane is made from
biocompatible polymers.
E.g. Cellulose acetate
b) GEL DIFFUSION CONTROLLED DELIVERY SYSTEM:
The main feature of this system is that the drug core is enclosed with a partially
soluble membrane.
E.g. Carboxy methyl cellulose
c) MUCOADHESIVE DRUG DELIVERY SYSTEM:
It interacts with the mucus layer covering the mucosal epithelial surface, mucin
molecules & increase the residence time of the dosage form at the site of
absorption. In this, a polymer is required to produce an adhesion interaction with a
biological membrane.
E.g. carbopol
18
2. TRANSDERMAL DRUG DELIVERY SYSTEM:
TDDS is defined as self contained, self discrete dosage forms, which when applied
to the intact skin delivers the drug at a controlled rate to the systemic circulation. In
this, polymer matrix plays a major role. It releases the drug from the device to the
skin.
E.g. Natural polymers
Cellulose derivative, gelatin, shellac, waxes, gums
Synthetic polymers
Polyvinyl chloride, polyethylene, polyvinyl pyrrolidone
3. OCULAR DRUG DELIVERY SYSTEM:
It allows prolonged contact of drug with corneal surface of eye. The example
for ODDS is pilocarpine in the treatment of glaucoma.
In this mucoadhesive polymers are used as barriers to control the drug
release.
E.g. Polyacrylic acid
Copolymers of acetate vinyl & ethyl
B. OTHER APPLICATIONS
1) DRUG DELIVERY OF VARIOUS CONTRACEPTIVES & HORMONES:
E.g. medroxyprogesterone acetate – vaginal contraceptive ring
It consists of a drug reservoir & polymer coating material. Through this layer the
drug releases slowly.
2) DRUG DELIVERY AND HE TREATMENT OF DIABETES
Here the polymer will act as barrier between blood stream & insulin
E.g. polyacrylamide or N,N-dimethylaminoethylmethacrylate
3) APPLICATIONS OF POLYMERS IN SOLID DOSAGE FORMS:
IN TABLETS
Polymers like methyl cellulose, hydroxyl ethyl cellulose, hydroxyl ethyl
methylcellulose are used as binders.
Polymers like carboxyl methyl cellulose sodium is used as disintegrating agent.
Polymers like all the cellulose derivative are used as coating materials.
Polymers like cellulose acetate phthalate, hydroxyl propyl methyl cellulose
phthalate, polyvinyl acetate phthalate are used as enteric coating material
IN CAPSULES
Gelatin, a natural polymer which is the major ingredient in the manufacturing of
22
4) APPLICATIONS OF POLYMERS IN LIQUID DOSAGE FORMS:
IN SUSPENSIONS
Polymers like Acacia, Tragacanth, Cellulose derivative, Xanthum gum are used as
suspending agents. They should be selected based on their characters like PH,
solubility & concentration. They enhances the dispersion of solids in liquids.
IN EMULSIONS
Polymers like Tragacanth, Spans, Tweens are used as emulsifying agents.
23
5) Polymers can be used as film coatings to mask the unpleasant taste of a drug &
to modify drug release characteristics.
6) Polyanhydrides are used in CDDS because of their unique property of surface
erosion.
7) Hyaluronic acid is used in controlled release ophthalmic preparations.
8) Wide variety of polymers like natural gums are using as thickening agents.
E.g. polyethylene glycol, carbomer
9) Some of the polymers are using as protective colloids to stabilize suspensions &
emulsions. E.g. sodium alginate
10)Some polymers can be used as suppository bases E.g. polyethylene [email protected] 24
11)Some polymers are used in uterus therapeutic system E.g. silicone
12)Copolymers of lactide & glycolide, silicone are using in implantation therapeutic
system.
13)Polyurethanes can be used for elasticity
14)Polymethyl methacrylate for physical strength & transparency.
15)Polyvinyl alcohol for hydrophilicity & strength
16) In addition to polymers being used as excipients, some drugs themselves are
polymers including insulin, heparin & its antagonist, protamine sulfate, plasma
expander like dextran, normal human serum albumin, bulk laxatives like methyl
cellulose & sodium carboxy methyl cellulose.
25
Thus, polymers are essential to the
Dispensing pharmacist
Manufacturing pharmacist
Research pharmacist
RECENT DEVELOPMENTS IN USE OF POLYMERS FOR DRUG DELIVERY SYSTEMS
• Some researchers have prepared collagen poly-HEMA (polyhydroxyethylmethacrylate)
hydrogels as an implant for delivering anti cancer drugs such as 5-fluoro uracil,
mitomycin & bleomycin for solid fibro sarcoma in rat model.
• The same hydrogels have been used with some modifications for the delivery of model
protein bovine serum albumin& vaccines such as Tetanus & Diphtheria toxoids in mice.
• The recent technique in the use of polymers is polymeric pro-drug
The polymeric prodrug can be regarded as drug delivery system that
exhibit their therapeutic activity by means of releasing smaller therapeutic
drug molecules from a polymer chain molecule for a prolonged period of
time which results in enhanced pharmacokinetic behaviour by increasing the
t1/2, bioavailability & hence prolonged pharmacological action.
E.g. Anti cancer drugs
REFERENCE
• www.globalresearchonline.net
• Pharmaceutical applications of polymers for drug delivery by D. Jones
• www.wikipedia.com
• www.google.co.in
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