DOSAGE FORM DESIGN- V

NOVEL DRUG DELIVERY SYSTEM

Course code: LBPH 3532

CLO-1
Polymerization System

B.Pharm(Hons)

Lecturer: Neha Unnisa

Upon completion of this chapter, you should be
able to:
• Types of polymers
• General characteristics
• Applications
• Classification
 INTRODUCTION
• A chemical compound that is made of small molecules that
are arranged in a simple repeating structure to form a larger
molecule.
• Advances in polymer science have led to the development of
novel drug delivery systems.
• The introduction of new polymers has resulted in
development of polymers with unique properties.
• Initially polymers were used as solubilisers, stabilizers
and mechanical supports for sustained release of
drugs.
• Over a period of time, the functionalities of polymers
have changed.
• Polymers have been synthesized to suit specific needs
or rather solve specific problems associated with
development of drug delivery systems.
• So there is need to understand the role of polymers.
Natural polymers 
• These are obtained from nature, e.g., plant , animal origin etc.
• Biologically degradable polymers are also present, called biopolymers.
Examples- Cellulose, Xanthan Gum, Pectin, Chitosan, Dextran, Carrageenan, Guar
Gum, Protein etc.
They can be divided into Polypeptides, Sugars, and Nucleic acids.
Synthetic polymers
These have been prepared by humans in laboratories and are currently
produced industrially.
Example – Plastic, PVC etc
Semi-synthetic polymers
These polymers are derived from natural sources and undergo further
chemical/physical treatment before attaining their final form.
Example – Rayon, Terylene etc
Classification based biodegradability:

• Biodegradable polymers can be defined as polymers that are

degradable in vivo, either enzymatically or non-enzymatically, to
produce biocompatible or nontoxic by-products.
• These polymers can be metabolized and excreted through
normal physiological pathways.
• They are classified into three groups,    synthetic, semi synthetic
and natural
Advantage of biodegradable polymers:
• Provides a drug at a constant rate of controlled release owes a prescribed period of
time.
• Degrade into non-toxic and absorbable subunits which would be subsequently
metabolized.
• Not exhibit dose dumping at any time period and polymer would retain its
characteristics until after depletion of the drug.
• Biodegradable system eliminates the necessity for surgical removal of implanted
device following depletion of a drug.
• Broken down into biologically acceptable molecules that are metabolized and
removed from the body through normal metabolic pathways.
 Disadvantage of biodegradable polymers:
• Exhibit substantial dose dumping at some point following implantations.
• A “burst effect” or high initial drug release soon after administration is typical of most
system.
• Injection of a particulate form are non-retrievable.
 Factors Influence the Polymer
Degradation Behavior:
• Chemical Structure and its Composition of polymer
• Distribution of Repeat Units in Multimers
• Molecular Weight of  polymer Site of Implantation
• Annealing
• Physiochemical Factors of polymer (shape, size)
• Mechanism of Hydrolysis (enzymes vs water)
• Presence of Chain Defects
• Presence of Unexpected Units
• Configurational Structure
Factors that accelerate polymer degradation:
A) More hydrophilic end groups.
B) More hydrophilic backbone.
C) More reactive hydrolytic groups in the backbone.
D) Less crystallinity.
E) High porosity.
Classification of polymers based on
structure
Linear Polymers – Monomers join with each other to
form long straight chains.
Example – Poly Vinyl Chloride or PVC is a linear
polymer
Branched Chain Polymers – These polymers are made
of branching of linear chains of monomers.
• They have low melting points and low densities.
Example – Low-density polythene
Cross-linked Polymers/Network Polymers – These
polymers are formed by bi-functional and tri-functional
monomers with a strong covalent bond between the
various linear polymer chains.
• These polymers are brittle by nature.
Example – Melamine.
 Classification of Polymers based on
molecular forces
Thermoplastics – These polymers become soft on the application of heat and thus can be
molded in the desired shape.
Example – Polystyrene, polyethylene, polypropylene
Thermosets – These polymers have their individual chains bonded covalently during
polymerization, or by application of heat or chemical treatment.
• Once set, their shape cannot be changed.
• They resist subsequent mechanical deformation or heat softening or solvent attack.
• Good for adhesive purposes, coatings etc.
Example – Fiberglas, melamine
Elastomers – Polymer chains that are elastic and can be stretched like rubber.
They have weak intermolecular forces between the chains and may have cross bonds.
Example – Vulcanized rubber
Fibers – They have strong intermolecular forces – either hydrogen bonds or dipole-dipole
interactions between their chains.
These chains have a high tensile strength and less elasticity, and high melting points.
Example – Silk, Nylon etc.
 Classification of Polymers based on mode
of polymerization:
• Addition polymers: formed by the repeated addition of monomer
molecules, the monomers are unsaturated hydrocarbons.
• There is no elimination product in the reactions. 
Example : Vinyl chloride to Polyvinyl chloride.

• Condensation polymers:  formed by repeated Condensation between

two different bi-functional or tri-functional monomeric units, along
with the formation of elimination product like water, NH3, HCl etc.
 Classification of Polymers based on the type of
monomer involved in the structure
Homo-polymer
 When the same monomer is repeated throughout the chain of the
polymer.
Co-polymer
• When there are at least 2 different monomers along the entire chain.
• Co-polymers can be further divided into multiple types.
• A controlled arrangement of monomers in a copolymer is called a
sequence controlled polymer.
NATURAL POLYMERS
Cellulose Derivatives:
• Cellulose is the most naturally occurring biopolymer.
• Various natural fibers such as cotton and higher plants have cellulose as their main
constituent.
• It consists of long chains of anhydro-D-glucopyranose units (AGU) with each
cellulose molecule having 3 hydroxyl groups per AGU, with the exception of the
terminal ends.
• Cellulose is immiscible in water and most common solvents; the poor solubility is
attributed primarily to the strong intra molecular and intermolecular hydrogen
bonding between the individual chains.
• In spite of its poor solubility characteristics, cellulose is used in a wide range of
applications including composites, netting, upholstery, paper, coatings, packing etc.
Examples of Cellulose derivatives and its drug delivery
applications?
Starch:
• Modified starch was tested for general applicability of a new
pregelatinized starch product in directly compressible controlled- release
matrix systems.
• Prepared by enzymatic degradation of potato starch followed by
precipitation, filtration and washing with ethanol.
Advantages:
• Ease of tablet preparation
• Potential for zero-order for an extended period of time and
• Ability to incorporate high percentages of drugs with different
physicochemical properties.
Hyaluronic acid:
• Also called as Hyaluronan and Hyaluronate (HA) and Sodium Hyaluronate
(SA) is sodium salt form of hyaluronic acid
• Biodegradable
• Biocompatible
• Viscoelastic linear polysaccharide of a wide molecular weight range (1000 to
10,000,000 Da).
• Serves important biological functions in bacteria and higher animals including
humans.
• HA solutions are characteristically viscoelastic and pseudoplastic.
• The viscoelastic property of HA solutions that is important in its use as a
biomaterial is controlled by the concentration and M/Wt of the hyaluronic
acid chains.
• As a microcapsule, it can be used for targeted drug delivery. 
 Cyclodextrin:
• Cyclic oligosaccharides consisting of 6 to 8 glucose units
joined through α-1, 4 glucosidic bonds.
• Cyclodextrins remains intact during their passage throughout
the stomach and small intestine of the GI tract.
• However, in colon, they undergo fermentation in the presence
of vast colonic microflora's into small monosaccharide and
thus absorbed from these regions.
• β- Cyclodextrins are degraded to a very small extent in the
small intestine but are completely digested in the large
intestine.
• Most of the bacterial strains found abundantly in human
beings are capable of degrading cyclodextrins polysaccharide.
 Collagen:
• Major natural protein component in mammals that is fabricated from
glycine-proline- hydroxy proline repeats to form a triple helix molecular
structure.
• So far, 19 types of collagen molecules have been isolated, characterized, and
reported in both medical and pharmaceutical applications.
• Collagen has been widely used in pharmaceutical applications due to the
fulfillment of many requirements of a drug delivery system such as good
biocompatibility, low antigenicity, and degradability upon implantation.
• Collagen gels are one of the 1st natural polymers to be used as a promising
matrix for drug delivery and tissue engineering.
• Biodegradable collagen-based systems have served as 3D scaffold for cell
culture, survival of transfected fibroblasts, and gene therapy.
• In this case, collagen scaffolds were fabricated through introducing various
chemical cross-linking agents (i.e., formaldehyde, glutaraldehyde,
carbodiimide) or by physical treatments (i.e., UV irradiation, freeze-drying,
and heating)
Gelatin:
• Common natural polymer (water miscible polymer) or protein which is
normally produced by denaturing collagen.
• Used in pharmaceutical and medical applications due to its outstanding
properties such as biodegradability, biocompatibility, and low antigenicity.
• In addition, gelatin can be easy to manipulate due to its isoelectric point
that allows it to change from negative to positive charge in an appropriate
physiological environment or during the fabrication, a property that has
found it being very attractive to many pharmaceutical researchers.
• Gelatin is one of the natural polymers used as support material for gene
delivery, cell culture, and more recently tissue engineering.
• Gelatin-based systems have the ability to control release of bioactive
agents such as drugs, proteins, and dual growth factors.
Albumin:
• Serum albumin was conjugated to poly-(ethylene glycol) (PEG) and
cross-linked to form mono- PEGgylated albumin Hydrogels.
• These Hydrogels were used as a basis for drug carrying tissue
engineering scaffold materials, based on the natural affinity of
various drugs and compounds for the tethered albumin in the
polymer network.
• It is easy to purify, soluble in water which makes it convenient to
delivery by injection
• Considered as an ideal candidate for nanoparticle preparation 
Alginate:
• Alginate also serves as an example of a naturally occurring linear
polysaccharide.
• Extracted from algae, seaweed, and bacteria.
• The fundamental chemical structure of alginate is composed of (1–4)-b- D-
mannuronic acid (M) and (1–4)-a-L-guluronic acid (G) units in the form of
homo polymeric (MM- or GG-blocks) and hetero polymeric sequences (MG or
GM-blocks).
• Applications in drug delivery due to its water solubility, biocompatibility,
biodegradability, low toxicity, relatively low cost, non- immunogenicity, gelling
ability, stabilizing properties, and high viscosity in aqueous solutions.
• Since alginate is anionic, fabrication of alginate Hydrogels has successively
been achieved through a reaction with cross-linking agents such as divalent
or trivalent cations mainly calcium ions, water-soluble carbodiimide, and/or
glutaraldehyde.
Dextrin:
• Natural linear polymer of glucose linked by a 1–6 linked- glucoyranoside,
and some branching of 1, 3 linked side-chains.
• Synthesized from sucrose by certain lactic-acid bacteria, the best-known
being Leuconostoc mesenteroides and Streptococcus mutans.
• Two commercial preparations: Dextran 40 (kDa) and dextran 70 (kDa)
• In pharmaceutical technology, dextran has been used as model of drug
delivery due to its unique characteristics that differentiate it from other
types of polysaccharide.
• This includes water solubility, biocompatibility, and biodegradability.
• In advanced studies, dextran has been regarded as a potential
polysaccharide polymer that can sustain the delivery of vaccines, proteins
and drugs. 
Chitosan:
• Natural polyatomic copolymer consisting of glucosamine and N-acetyl
glucosamine units.
• Obtained by deactivation of chitin derived from the exoskeleton of
crustaceans.
• Valuable properties- biocompatible, Biodegradable, nontoxic.
• The cationic character and the potential functional group make it an
attractive biopolymer for many biomedical and pharmaceutical
applications.
• As a pharmaceutical excipient, chitosan has been used in many
formulations like powders, emulsions, gels and tablets.
• Chitosan also shows antimicrobial properties and Mucoadhesive
properties.
Poly ethylene glycol (PEG)
• In general, a low polydispersity index (PDI) is a prerequisite for the polymer
to have pharmaceutical applications.
• A PDI value below 1.1 makes the polymer more homogenous so that it
provides reliable residence time in the body .
• All these prerequisites are fulfilled by PEG, since it has PDI of 1.01.
• This holds good for low molecular weight PEGs.
• PEG is synthesized by the interaction of ethylene oxide with water, ethylene
glycol, or ethylene glycol oligomers.
• PEG shows a high solubility in organic solvents and, therefore, end-group
modifications are relatively easy.
• PEG is suitable for biological applications because it is soluble in water and
has low intrinsic toxicity.
• The high hydrophilic nature of PEG enhances the solubility of hydrophobic
drugs or carriers when conjugated with them.
• Enhances the physical and chemical stability of drugs and prevents aggregation
of the drugs in vivo, as well as during storage
• Reducing the aggregation of red blood cells and so improves the blood
compatibility of PEG copolymers that are implanted as cardiovascular devices
such as stents. It is mainly used in storage of blood and organs.
• Both temperature-responsive and chemically crosslinked hydrogels have been
formed from PEG.
• Temperature-responsive systems have become increasingly attractive as
injectable drug delivery systems.
• Chemically crosslinked systems have also been studied for in situ photo
polymerization.
Polyvinyl pyrrolidone (PVP)
• Polyvinyl pyrrolidone is a water soluble polymer having molecular
weight ranging from 40,000 to 360,000.
• Synthesized by polymerization of vinylpyrrolidone in water or
isopropanol.
• Available in different grades based on molecular weights.
• Used as a binder in tablet formulations when compared to other
binders, wet granulation with PVP having a molecular weight of
25,000 to 90,000 generally gives harder granulates with good
flowability, higher binding and low friability.
• Increases the dissolution of the active ingredient. 
Polyacrylic acid (PAA)
• Biodegradable water soluble polymer with various industrial applications,
including as a super adsorbent (e.g., in disposable nappies), in water
treatment, etc. 
• Poly acrylic acid (PAA) copolymers modified with block-copolymers of poly
ethylene oxide (PEO) and poly propylene oxide (PPO) have a wide range of
medicinal applications as their components are considered
pharmaceutically safe.
• Exists as a liquid at pH 5 and as a gel at pH 7.
• Permeation of cations into the gelled polymer converts the gel back to a
liquid .
• Ideal for ocular delivery of ribozymes to the corneal epithelium as a drug
delivery vehicle.
 Polyacrylamides
• Polyacrylamide, is a synthetic polymer derived from
acrylamide monomer which was originally introduced for use
as a support matrix for electrophoresis in 1959.
• Non-toxic
• FDA allows Polyacrylamide (≤ 0.2% acrylamide monomer) to
be used as a film former in the imprinting of soft-shell gelatin
capsules.
• Polyacrylamides were first used as an implantable carrier for
sustained delivery of insulin to lengthen the life of diabetic
rats.
N-(2-Hydroxypropyl) methacrylamide
(HPMA)
• The polymeric systems that have been very successfully used
for passive drug targeting purposes are copolymers based on
N-(2-hydroxypropyl) methacrylamide (HPMA).
• HPMA copolymers were initially developed as plasma
expanders
• Highly hydrophilic
• Non-immunogenic
• Non-toxic
• Reside in the circulation well.
CHARACTERISTICS OF POLYMER
APPLICATION
Thank you