Polymer Science

Neha P. Dave DEFINITION Polymers are very large molecules made when hundreds of monomers join together to form long chains.

The word ‘polymer’ comes from the Greek words poly (meaning ‘many’) and meros (meaning ‘parts’).

Example: POLYBUTADIENE = (BUTADIENE+ BUTADIENE+...... )n Where n = 4,000 INTRODUCTION

• Polymers are complex and giant molecules usually with carbons building the backbone, different from low molecular weight compounds. • The small individual repeating units/molecules are known as monomers(means single part). • Imagine that a monomer can be represented by the letter A. Then a polymer made of that monomer would have the structure: -A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A • This kind of polymer is known as HOMOPOLYMER. (According to their properties & characteristics.) 1. Natural and Synthetic Polymers

 Polymers which are isolated from natural materials, are called as ‘natural polymers’. E.g. : Cotton, silk, wool, rubber.

natural rubber  Polymers synthesized from low molecular weight compounds, are called as, ‘synthetic polymers’. E.g. polyethylene, nylon, terylene.

Polyethylene Semi synthetic polymers : • Geletin , fibrinogen chitin &chitoson , dextran, alginate NATURAL RUBBER- Hevea brasiilensis 2)BASED ON PRESENCE OF CARBON ATOM:

 A Polymer whose backbone chain is essentially made of carbon atoms is termed an ‘Organic polymer’. Examples- cellulose, proteins, polyethylene, nylons.

 A Polymer which does not have carbon atom in their chain is termed as ‘Inorganic polymer’ . Examples- Glass and silicone rubber 3. Classification by Monomer Composition

Homopolymer Copolymer

Block Graft Alternating Statistical

Homopolymer Consist of only one type of constitutional repeating unit (A) AAAAAAAAAAAAAAA Copolymer Consists of two or more constitutional repeating units (A.B ) 4. Based on Microstructure  Statistical copolymer (Random) ABAABABBBAABAABB two or more different repeating unit are distributed randomly  Alternating copolymer ABABABABABABABAB are made of alternating sequences of the different monomers  Block copolymer AAAAAAAAABBBBBBBBB long sequences of a monomer are followedby long sequences of another monomer  Graft copolymer AAAAAAAAAAAAAAAAAA B B B B B B (d) 5. Based on Chain structure (molecular architecture) Linear chains :a polymer consisting of a single continuous chain of repeat units Branched chains :a polymer that includes side chains of repeat units connecting onto the main chain of repeat units Hyper branched polymer :consist of a constitutional repeating unit including a branching groups Cross linked polymer :a polymer that includes interconnections between chains Net work polymer :a cross linked polymer that includes numerous interconnections between chains

Linear Branched Cross-linked Network

Direction of increasing strength 6. Based on physical property related to heating  Some polymer are soften on heating and can be converted into any shape that they can retain on cooling.  Such polymer that soften on heating and stiffen on cooling are termed as `thermoplastic’ polymers. Ex. Polyethylene, PVC, nylon, sealing wax.  Polymer that become an infusible and insoluble mass on heating are called ‘thermosetting’ polymers. Plastics made of these polymers cannot be stretched, are rigid and have a high melting point. 7. Classification by applications

 Polymer is shaped into hard and tough utility articles by application of heat and pressure, is known as ‘plastics’. E.g. polysterene, PVC, polymethyl methacrylate.  When plastics are vulcanised into rubbery products exhibiting good strength and elongation, polymers are known as ‘elastomers’. E.g. silicone rubber, natural rubber, synthetic rubber, etc.  Long filament like material whose length is atleast 100 times it’s diameter, polymers are said to be ‘fibres’. E.g. Nylon, terylene.  Polymers used as adhesives, potting compounds, sealants, etc., in a liquid form are described as ‘liquid resins’. E.g. Epoxy adhesives and polysulphides sealants. 8. Classification Based on Kinetics or Mechanism A) Step-growth B) Chain-growth

9. BASED ON DEGRADATION OF POLYMER:

. Biodegradable polymers: It can be defined as polymers comprised of monomers linked to one another through functional group and have unstable linkage in the backbone. eg. Collagen, Albumin,Casein etc.

.Non biodgradable polymers: Polymerization mechanisms Forming large molecules from small molecules – Polymerization. There are two basic kinds of polymerization reactions:

A)condensation(example: curing of concrete) or step growth B)Chain growth (example, formation of PVC pipe)

- Step-growth polymerization Step-Growth Polymerization

Stage 1 n n Consumption of monomer

Stage 2

Combination of small fragments

Stage 3

Reaction of oligomers to give high molecular weight polymer Chain-growth polymerization Chain growth polymerization involves an active chain site which reacts with an unsaturated (or heterocyclic) monomer such that the active site is recovered at the chain end. Chain polymerization

Radical polym. Ionic polym. The C=C is prefer the Polym. by R.P. and also can be used in Anionic polym. Cationic polym. the steric hindrance of Electron with drawing Electron donating the substituent substituent decreasing substituent increasing the electron density on the electron density on the double bond and the double bond and facilitate the attack of facilitate the attack of anionic species cationic species such as cyano and such as alkoxy, alkyl, alkenyl, carbonyl and phenyl δ+ δ- δ- δ+ CH =CH Y 2 CH2 =CH Y

X X X radical cationic anionic COMMON SYNTHESIS STEPS FOR DIFFERENT TECHNIQUES: 1)Initiation ; 2)Propagation; 3)Termination; -Coupling ; -Disproportionation ; -Chain transfer; -Inhibitor; (1)INITIATION: • Initiation in free radical polymerization involves first the generation of free radicals, which then attacks the double bond in the monomer molecule, resulting in the following chemical change;

• R + CH2 = CH + R-CH2-CH ! ! free radicals X X monomer molecule

• The free radical site is now shifted from the initiator fragment to the monomer unit. • The monomer initiating polymerization is an exothermic process. (2)PROPAGATION:

• In these step, the radical site at the first monomer unit attacks the double bond of a fresh monomer molecule.

• This results in the linking up of the second monomer unit to the first and the transfer of the radical site from the first monomer unit to the second , by the unpaired electron transfer process.

• This process involving a continuing attack in fresh monomer molecules. (3)TERMINATION: • In this process any further addition of the monomer unit to the growing chain is stopped & the growth of the polymer chain is arrested by one of the following reaction. Coupling ; • The coupling of the lone electron present in each chain to form an electron pair and, thus nullify their reactiveness.

Disproportionation ; • One H from one growing chain is abstracted by the other growing chain & utilized by the lone electron for getting stabilized.

Inhibitor; • MH is known as a chain transfer agent, and addition of controlled amounts of MH to the polymerization reaction can be used to control molecular weight of the polymers. Characteristics of polymer

 Low Density.  Low coefficient of friction.  Good corrosion resistance.  Good mould ability.  Excellent surface finish can be obtained.  Economical.  Poor tensile strength.  Low mechanical properties.  Poor temperature resistance.  Can be produced transparent or in different colours Polymer properties

Physical Properties Mechanical Properties • Specific Gravity • Strength (Tensile and • Mold Shrinkage (in Flexural) flow, cross-flow, and • Modulus (Tensile and thickness directions) Flexural) • Elongation • Hardness • Impact Resistance Environmental Properties Thermal Properties • Chemical Resistance • Heat Deflection • UV Resistance Temperature • Flame Resistance (UL • VICAT Softening Rating) Temperature • Oxygen Index • Glass Transition Temp • Water Absorption • Heat Capacity • Thermal Conductivity STRUCTURAL POLYMER PROPERTIES • Mol. wt of polymer, this affect over all properties. the Mol.wt increases with increased tensile strength & resistance. • Force of attraction between polymer chain is high, crystals are formed. • Secondary interaction between atom on side chain stiffing the chain and increase strength. • Polymer appears translucent. • Heating of crystalline material above their melting point cause individual polymer chain to become mobile and transparent. • Density of polymer is increases by increasing crystalline content. Solubility decreases with the closer and more closer and more regular packing of polymer chain. CHEMICAL PROPERTIES • Polymer undergo significant degradation in body. • High crystallinity can increase polymer stability. • Ingredient can be use to improve polymer formation and enhance the overall properties. • Polymer properties may affect interaction with surrounding. • Polymer has been found into shape suitable for intended, sterilization process. Morphological Properties Crystallinity

•A synthetic polymer may be described as crystalline if it contains regions of three-dimensional ordering on atomic (rather than macromolecular) length scales, usually arising from intramolecular folding and/or stacking of adjacent chains.

•Synthetic polymers may consist of both crystalline and amorphous regions; the degree of crystallinity may be expressed in terms of a weight fraction or volume fraction of crystalline material.

•The driving force for crystallization is a closer packing of the polymer chains with consequent enhancement of intermolecular attractions. Bulk properties Tensile Strength The tensile strength of a material quantifies how much stress the material will endure before failing. This is very important in applications that rely upon polymer's physical strength or durability. In general tensile strength increases with polymer length. Transport Properties

Transport properties such as diffusivity relate to how rapidly molecules move through the polymer matrix. These are very important in many applications of polymers for films and membranes. Youngs Modulus of Elasticity

This parameter quantifies the elasticity of the polymer. It is defined, for small strains, as the ratio of rate of change of stress to strain. Like tensile strength this is highly relevant in polymer applications involving the physical properties of polymers Young's modulus, E, can be calculated by dividing the tensile stress by the tensile strain:

where E is the Young's modulus (modulus of elasticity) measured in pascals; F is the force applied to the object;

A0 is the original cross-sectional area through which the force is applied; ΔL is the amount by which the length of the object changes;

L0 is the original length of the object. Pure Component Phase Behavior Melting Point •The term "melting point" when applied to polymers suggests not a solid-liquid phase transition but a transition from a crystalline or semi-crystalline phase to a solid amorphous phase.

•It is abbreviated as "Tm", is more properly called the "crystalline melting temperature". •Among synthetic polymers, crystalline melting is only discussed with regard to thermoplastics, as thermosetting polymers will decompose at high temperatures rather than melt. Glass Transition Temperature

•A parameter of particular interest in synthetic polymer manufacturing is the glass transition temperature (Tg), which describes the temperature at which amorphous polymers undergo a second order phase transition from a rubbery, viscous amorphous solid to a brittle, glassy amorphous solid. •The glass transition temperature may be engineered by altering the degree of branching or cross-linking in the polymer or by the addition of plasticizer. Solution properties of polymers Polydispersity Nearly all synthetic polymers and naturally occurring macromolecules possess a range of molecular weights. The exceptions to this are proteins and natural polypeptides. The molecular weight is thus an average molecular weight and depending on the experimental method used to measure it. Viscosity The viscosity of a polymer solution not only depends on its concentration but also on polymer–solvent interactions, charge interactions and the binding of small molecules. The intrinsic viscosity of solutions of linear high-molecular weight polymers is proportional to the molecular weight M of the polymer as given by the Staudinger equation: [η] = KMa Properties of polymer gels •A gel is a polymer–solvent system containing a three dimensional network which can be formed by swelling of solid polymer or by reduction in the solubility of the polymer in the solution. •When gels are formed from solutions, each system is characterized by a critical concentration of gelation below which a gel is not formed. •Gels can be irreversible or reversible systems depending on the nature of the bonds between the chains of the network. Fabrication of polymers in pharmaceuticals FABRICATION PROCESS

1) EXTRUSION 2) INJECTION MOULDING 3) COMPRESSION MOULDIND 4) PALTRUSION 5) SPINNING 6) TWO ROLL MILLING 7) INTERNAL MIXING 1. EXTRUSION • Extrusion is a process used to create objects of a fixed cross- sectional profile. A material is pushed or drawn through a die of the desired cross-section. The two main advantages of this process over other manufacturing processes is its ability to create very complex cross-sections and work materials that are brittle, because the material only encounters compressive and shear stresses. It also forms finished parts with an excellent surface finish. • Extrusion may be continuous or semi-continuous. • The extrusion process can be done with the material hot or cold. • Commonly extruded materials include metals, polymers, ceramics, concrete and foodstuffs. A. HOT EXTRUSION

• Hot extrusion is done at an elevated temperature to keep the material from work hardening and to make it easier to push the material through the die. • Most hot extrusions are done on horizontal hydraulic presses that range from 250 to 12,000 tons. Pressures range from 30 to 700 MPa (4,400 to 102,000 psi), therefore lubrication is required, which can be oil or graphite for lower temperature extrusions, or glass powder for higher temperature extrusions. B. COLD EXTRUSION

• Cold extrusion is done at room temperature or near room temperature. • The advantages of this over hot extrusion are the lack of oxidation, higher strength due to cold working, closer tolerances, good surface finish, and fast extrusion speeds if the material is subject to hot shortness. • Examples of products produced by this process are: collapsible tubes, fire extinguisher cases, shock absorber cylinders, automotive pistons, and gear blanks. C. WARM EXTRUSION • Warm extrusion is done above room temperature, but below the recrystallization temperature of the material the temperatures ranges from 800 to 1800 °F (424 to 975 °C). • It is usually used to achieve the proper balance of required forces, ductility and final extrusion properties.

Schematic diagram of a simple extrusion machine 2. INJECTION MOULDING • Injection molding is a manufacturing process for producing parts from both thermoplastic and thermosetting plastic materials. • Material is fed into a heated barrel, mixed, and forced into a mold cavity where it cools and hardens to the configuration of the mold cavity. • After a product is designed, usually by an industrial designer or an engineer, molds are made by a moldmaker (or toolmaker) from metal, usually either steel or aluminium, and precision- machined to form the features of the desired part. • Injection molding is widely used for manufacturing a variety of parts, from the smallest component to entire body panels of cars.

INJECTION PROCESS

• Small injection molder showing hopper, nozzle and die area With Injection Molding, granular plastic is fed by gravity from a hopper into a heated barrel. • As the granules are slowly moved forward by a screw-type plunger, the plastic is forced into a heated chamber, where it is melted. • As the plunger advances, the melted plastic is forced through a nozzle that rests against the mold, allowing it to enter the mold cavity through a gate and runner system. The mold remains cold so the plastic solidifies almost as soon as the mold is filled. A. INJECTION MOLDING CYCLE • The sequence of events during the injection mold of a plastic part is called the injection molding cycle. • The cycle begins when the mold closes, followed by the injection of the polymer into the mold cavity. • Once the cavity is filled, a holding pressure is maintained to compensate for material shrinkage. • In the next step, the screw turns, feeding the next shot to the front screw. This causes the screw to retract as the next shot is prepared. Once the part is sufficiently cool, the mold opens and the part is ejected B. TIME FUNCTION

• The time it takes to make a product using injection molding can be calculated by adding: • Twice the Mold Open/Close Time (2M) + Injection Time (T) + Cooling Time (C) + Ejection Time (E)

Where T is found by dividing: Mold Size (S) / Flow Rate (F)

Total time = 2M + T + C + E T = V/R

V = Mold cavity size (in3) R = Material flow rate (in3/min)

The total cycle time can be calculated using tcycle = tclosing + tcooling + tejection • Schematic diagram of injection-molding machine

Schematic diagram of injection-molding machine 3. COMPRESSION MOULDING  A method of molding in which the molding material, generally preheated, is first placed in an open, heated mold cavity.  The mold is closed with a top force or plug member, pressure is applied to force the material into contact with all mold areas, and heat and pressure are maintained until the molding material has cured.  The process employs thermosetting resins in a partially cured stage, either in the form of granules, putty-like masses, or preforms.  Compression molding is a high-volume, high-pressure method suitable for molding complex, high-strength fibreglass reinforcements.

 Advanced composite thermoplastics can also be compression molded with unidirectional tapes, woven fabrics, randomly orientated fiber mat or chopped strand.

 The advantage of compression molding is its ability to mold large, fairly intricate parts.

 Compression molding produces fewer knit lines and less fiber- length degradation than injection molding. 4. PALTRUSION • Paltrusion is a continuous process of manufacturing of composite materials with constant cross-section whereby reinforced fibers are pulled through a resin, possibly followed by a separate preforming system, and into a heated die, where the resin undergoes polymerization. Many resin types may be used in paltrusion including polyester, polyurethane, vinylester and epoxy. • But the technology isn't limited to thermosetting resins. More recently, pultrusion has also been successfully used with thermoplastic matrices such as polybutylene terephthalate (PBT) either by powder impregnation of the glass fiber or by surrounding it with sheet material of the thermoplastic matrix which is then molten up. 1 - Continuous roll of reinforced fibers/woven fiber mat 2 - Tension roller 3 - Resin bath 4 - Resin soaked fiber 5 - Die and heat source 6 - Pull mechanism 7 - Finished hardened fiber reinforced polymer 5. SPINNING • Spinning is manufacturing process for creating polymer fibers. It is a specialized form of extrusion that uses a spinneret to form multiple continuous filaments. There are four types of spinning: wet, dry, melt, and gel spinning. • Wet spinning is the oldest of the four processes. This process is used for polymers that need to be dissolved in a solvent to be spun. The spinneret is submerged in a chemical bath that causes the fiber to precipitate, and then solidify, as it emerges. The process gets its name from this "wet" bath. Acrylic, rayon, aramid, modacrylic, and spandex are produced via this process.[1] • Dry spinning is also used for polymer that must be dissolved in solvent. It differs in that the solidification is achieved through evaporating the solvent. This is usually achieved by a stream of air or inert gas. Because there is no precipitating liquid involved, the fiber does not need to be dried, and the solvent is more easily recovered. acetate, triacetate, acrylic, modacrylic, polybenzimidazole fiber, spandex, and vinyon are produced via this process. • Melt spinning is used for polymers that can be melted. The polymer solidifies by cooling after being extruded from the spinneret. Nylon, olefin, polyester, saran, and sulfar are produced via this process. Direct spinning • The direct spinning process is avoiding the stage of solid polymer pellets. The polymer melt is produced from the raw materials and from polymer finisher diretly pumped to the spinning mill. Direct spinning is mainly applied during production of polyester fibers and filaments and is dedicated to high production capacity (> 100 t/day). • Gel spinning, also known as dry-wet spinning, is used to obtain high strength or other special properties in the fibers. The polymer is in a "gel" state, only partially liquid, which keeps the polymer chains somewhat bound together. • The fibers are first air dried, then cooled further in a liquid bath. Some high strength polyethylene and aramid fibers are produced via this process. TWO ROLL MILLING

Pharmaceutical Applications of polymers  Polymers are used extensively in drug delivery, • e.g., for rheology control, control of drug release rate, stabilization of colloidal drug carriers, and solubilization of sparingly soluble drugs. • Many of the properties used in drug delivery rely on the chain-like nature of polymers. • The pharmaceutical applications of polymers range from their use as binders in tablets to viscosity and flow controlling agents in liquids, suspensions and emulsions. • Polymers can be used as film coatings to disguise the unpleasant taste of a drug, to enhance drug stability and to modify drug release characteristics Pharmaceutical applications

• Pharmaceutical excipients • Drug delivery • Hydrogels • Adhesive biomaterials Pharmaceutical excipients

• Coat tablets: Microcrystalline cellulose (MCC), sodium carboxyl methylcellulose (NaCMC), hydroxypropylmethycellulose (HPMC), hydroxyethylcellulose (HEC), Hydroxypropylcellulose (HPC), PEG, povidone • Binder: acacia, gelatin, sodium alginate, Microcrystalline cellulose • Disintegrants: Starch, carboxymethylstarch, micro crystalline cellulose, Na-carboxymethyl cellulose, cross linked pvp • Plasticizer :PEG, propylyn glycol • Thickening agents: xanthene gum (a natural gum polysaccharide used as a food additive and rheology modifier ) • Suspending agents: acacia, tragacanth, ethylcellulose, gelatin and sodium carboxymethylcellulose APPLICATIONS OF POLYMERS FOR CONVENTIONAL DOSAGE FORMS

Solid Dosage Forms Tablets Capsules Film Coatings of Solid Dosage Forms Disperse Systems Gels Applications of polymers in Medical  COMMERCIAL SUTURES  PROSTHETIC ORGANS  SILICON IMPLANTS  ARTIFICIAL SKIN In Packaging • Container • Bottles • Closers • Blisters polymers used in oral drug delivery

Criteria Categories Examples

Source Semi- Agarose, chitosan, gelatin natural/natural Hyaluronic acid Various gums (guar, hakea, xanthan, gellan, carragenan, pectin, and sodiumalginate) Synthetic Cellulose derivatives [CMC, thiolated CMC, sodium CMC, HEC, HPC, HPMC, MC, methylhydroxyethylcellulose] Poly(acrylic acid)-based polymers [CP, PC, PAA, polyacrylates, poly(methylvinylether-co- methacrylic acid), poly(2-hydroxyethyl methacrylate), poly(acrylic acid-co- ethylhexylacrylate), poly(methacrylate), poly(alkylcyanoacrylate), poly(isohexylcyanoacrylate), poly(isobutylcyanoacrylate), copolymer of acrylic acid and PEG] Others Poly(N-2-hydroxypropyl methacrylamide) (PHPMAm), polyoxyethylene, PVA, PVP, thiolated polymers Aqueous Water-soluble CP, HEC, HPC (waterb38 8C), HPMC (cold water), PAA, solubility sodium CMC, sodium alginate Water-insoluble Chitosan (soluble in dilute aqueous acids), EC, PC

Charge Cationic Aminodextran, chitosan, dimethylaminoethyl (DEAE)- dextran, trimethylated chitosan Anionic Chitosan-EDTA, CP, CMC, pectin, PAA, PC, sodium alginate, sodium CMC,xanthan gum Non-ionic Hydroxyethyl starch, HPC, poly(ethylene oxide), PVA, PVP, scleroglucan

Potential Covalent Cyanoacrylate bioadhesive forces Hydrogen bond Acrylates [hydroxylated methacrylate, poly(methacrylic acid)], CP, PC, PVA Electrostatic interaction Chitosan

10/5/2018 DEPARTMENTOF PHARMACEUTICS Tablet Coating Applications:

To mask the taste, odor, color of the drug. To provide physical and chemical protection for the drug. To control the release of the drug from the tablet. To protect the drug from the gastric environment of the stomach with an acid resistant enteric coating. To incorporate another drug or formula adjuvant in the coating to avoid chemical incompatibilities or to provide sequential drug release. To improve the pharmaceutical elegance by use of special colors and contrasting

10/5/2018 DEPARTMENTOF PHARMACEUTICS Disperse system

• To enhance the solubility of poorly soluble drugs solid dispersion is prepare by using water soluble polymers Examples: • Poly ethylene glycols (PEG) • Poly vinyl alcohol (PVA) • Poly vinyl pyrrolidone (PVP) • Mannitol etc…….

10/5/2018 DEPARTMENTOF PHARMACEUTICS Capsules

The polymeric capsules and hollow particles can be prepared from either monomeric starting materials or from oligomers and preformed polymers.  Mostly, the process involves a disperse oil phase in an aqueous continuous phase. The precipitation of polymeric materials at the oil-water interface causes each oil droplet to be enclosed within polymer shell.

10/5/2018 DEPARTMENTOF PHARMACEUTICS The interfacial polycondensation is used to prepare : poly(urea), poly(amide), or poly(ester) capsules by reaction between an oil-soluble monomer and water soluble monomers

Vinyl polymers such as polystyrene, acrylates and methacrylates have been used to prepare hollow or capsule polymer particles

10/5/2018 DEPARTMENTOF PHARMACEUTICS Hydrogels

• Highly swollen hydro gels: – cellulose derivatives – poly(vinyl alcohol) – poly(N-vinyl 2-pyrrolidone), PNVP – poly(ethylene glycol) • Moderately or poorly swollen hydro gels: - poly(hydroxyethyl methacrylate), PHEMA and derivatives • One may copolymerize a highly hydrophilic monomer with other less hydrophilic monomers to achieve desired swelling properties

10/5/2018 DEPARTMENTOF PHARMACEUTICS PLGA microparticles

10/5/2018 DEPARTMENTOF PHARMACEUTICS Transdermal Drug Product

• Over the last two decades more than 35 transdermal patch products have been approved globaly.

• Prescriptions for transdermal products have been used by ~12 million people worldwide for ailments ranging from bladder control to heart disease

10/5/2018 DEPARTMENTOF PHARMACEUTICS Transdermal Drug Delivery

Passive : • Matrix (Oxytrol, Vivelle Dot) • Reservior (Androderm, Duragesic) Active : • Iontophoresis • Electroporation • Sonophoresis • Heat or thermal energy • Microneedles

10/5/2018 DEPARTMENTOF PHARMACEUTICS Matrix Transdermal Systems

10/5/2018 DEPARTMENTOF PHARMACEUTICS Reservoir System Design

10/5/2018 DEPARTMENTOF PHARMACEUTICS BIODEGRADABLE POLYMERS Definition : Biodegradable polymers are defined as polymers comprised of monomers linked to one another through functional groups and have unstable links in the backbone. • They slowly disappear from the site of administration in response to a chemical reaction such as hydrolysis. • Material progressively releasing dissolved or dispersed drug, with ability of functioning for a temporary period and subsequently degrade in the biological fluids under a controlled mechanism, in to product easily eliminated in body metabolism pathway. ADVANTAGES

• Localized delivery of drug

• Sustained delivery of drug

• Stabilization of drug

• Decrease in dosing frequency

• Reduce side effects

• Improved patient compliance

• Controllable degradation rate MECHANISM OF BIODEGRADABLE POLYMERS

BIODEGRADATION

ENZYMATIC DEGRADATION HYDROLYSIS COMBINATION

BULK EROSION SURFACE EROSION Factors Influencing Biodegradation  CHEMICAL STRUCTURE (a) Functional Group (b) Hydrophobicity  MORPHOLOGY (a) Crosslink density  PARTICLE SIZE

TYPES OF BIODEGRADABLE POLYMERS  POLY ESTERS

 POLY PHOSPHO ESTERS

 POLY ANHYDRIDES

 POLY OLEFINS

 POLY AMIDES

 Pre Requisites of Bio degradable Polymers  BIO COMPATABILITY  MECHANICAL STRENGTH  STABILITY  BIO RESORBIBILITY  INERT Biodegradation : It is the process of chain cleavage, Found out by change in Mol.wt. Bioerosion : It is the sum of all process, leading to los of mass from a polymer matrix. Note : Hydrophobic polymers have to undergo degradation before Erosion takes place. Synthetic polymers used in pharmacy Carboxypolymethylene (Carbomer, Carbopol): • It is a high-molecular-weight polymer of acrylic acid, containing a high proportion of carboxyl groups • It is used as a suspending agent in pharmaceutical preparations, as a binding agent in tablets, and in the formulation of prolonged-acting tablets. Cellulose derivatives: Methylcellulose: It is slowly soluble in water. • Low-viscosity grades are used as emulsifiers for liquid paraffin and other mineral oils. High-viscosity grades are used as thickening agents for medicated jellies and as dispersing and thickening agents in suspensions. Hydroxypropylmethylcellulose (hypromellose) • It forms a viscous colloidal solution and is used in ophthalmic solutions to prolong the action of medicated eye drops and is employed as an artificial tear fluid. • Ethylhydroxyethylcellulose It is an ether of cellulose with both ethyl and hydroxyethyl substituents attached via ether linkages to the anhydroglucose rings. It swells in water to form a clear viscous colloidal solution. • Ethylmethylcellulose – contains ethyl and methyl groups, a 4% solution having approximately the same viscosity as acacia mucilage. • Hydroxyethylcellulose – is soluble in hot and cold water but does not gel. It has been used in ophthalmic solutions. More widely used for the latter, however, is hydroxypropylmethylcellulose (hypromellose) which is a mixed ether of cellulose containing 27–30% of –OCH3 groups and 4–7.5% of –OC3H6OH groups. It forms a viscous colloidal solution. There are various pharmaceutical grades. Polymer Characterization

The characterization of a polymer requires several parameters which need to be specified. This is because a polymer actually consists of a statistical distribution of chains of varying lengths, and each chain consists of monomer residues which affect its properties. A variety of lab techniques are used to determine the properties of polymers. Techniques such as wide angle X-ray scattering, small angle X-ray scattering, and small angle neutron scattering are used to determine the crystalline structure of polymers. Gel permeation chromatography is used to determine the number average molecular weight, weight average molecular weight, and polydispersity. FTIR and NMR can be used to determine composition. Thermal properties such as the glass transition temperature and melting point can be determined by differential scanning calorimetry and dynamic mechanical analysis. Pyrolysis followed by analysis of the fragments is one more technique for determining the possible structure of the polymer.

10/5/2018 81  Biocompatible evaluation techniques

i. Cytotoxic Testing The degree of cytotoxicity is determined by two means • Qualitative examination views cells microscopically for change in general morphology, detachment or cell lyses/membrane. • Quantative evaluation measurement of cell death,inhibition of cell growth,cell proliferation or colony formation. ii. Homocompatibility It is defined as the ability of the materials to coexist with blood without producing any toxicity, coagulation effects or complement activation. Materials should therefore neither initiate nor deactivate the processes involved in and associated with blood coagulation nor interfere with platelet morphology and function.

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