Pharmaceutical Polymers.



  • Polymer” is  derived from  Greek  words “Poly'' meaning many and  “Meros” meaning parts

  • Polymers have very large molecular weights and are made up of repeating units (or monomers) throughout their chains.  

  • Polymers are a subset of macromolecules.  

  • A monomer is a small molecule that combines with other molecules of the same or different types to form a polymer. 

  • If two, three, four, or five monomers are attached to each other, the product is known as a dimer, trimer, tetramer, or pentamer, respectively.  

  • An oligomer contains from 30 to 100 monomeric units. 

  • Products containing more than 200 monomers are called polymers. 

  • Polymers can have different chemical structures, physical properties, mechanical behavior, and thermal characteristics.

classification of polymers.

  • Polymers can be classified in different ways, as following,

    1. Based on the origin

    2. Based on the Backbone

    3. Based on the polymerization process

    4. Based on the types of monomer

    5. Based on the Line Structure 

    6. Based on thermal characteristics

    7. Based on interaction with water

    8. Based on stimulus response

    9. Based on Morphology

    10. Based on the presence of carbon (organic and inorganic)

Classification of Polymers Based on the Origin

  1. Natural Polymers 

  • Protein-based

    • Albumin, collagen, gelatin, etc. 

  • Polysaccharides

    • Agarose, alginate, carrageenan, chitosan, cyclodextrins,  dextran, hyaluronic acid, polysialic acid, etc.  

  1. Synthetic Polymers 

  • Biodegradable Polyesters

    • Poly(lactic acid) (PLA), poly  (glycolic acid) (PGA), poly  (hydroxybutyrate) (PHB), poly (Ɛ-caprolactone) (PCL), poly(β-malic acid) (PMA), poly(dioxanes) (PDA) etc. 

  • Polyanhydrides:  

    • Poly(sebacic  acid)  (PSBA),  poly(adipic  acid)  (PAPA),  poly(terephthalic acid) (PTA) and various copolymers etc. Polyamides include poly(imino carbonates) (PIC), polyamino acids (PAA), and others. 

  • Phosphorus-based

    • polyphosphates, polyphosphonates, polyphosphazenes, etc. 

  • Others:  

    • Poly(cyanoacrylates)  (PCA),  polyurethanes,  polyortho  esters, polydihydropyrans,polyacetals etc.

  • Non-biodegradable Cellulose derivatives

    • carboxymethyl cellulose (CMC),  ethylcellulose (EC), cellulose acetate (CA), cellulose acetate propionate (CAP), hydroxypropyl methylcellulose (HPMC), etc. 

  • Silicones

    • Polydimethylsiloxane (PDS), colloidal silica, etc. 

  • Acrylic  polymers:  

    • Polymethacrylates  (PMA),  poly(methyl  methacrylate)  (PMMA),  poly hydro(ethyl methacrylate) (PHEM) etc. 

  • Others

    • Polyvinyl pyrrolidone (PVP), Ethyl Vinyl Acetate (EVA), poloxamers, poloxamines, etc. 

  1. Semi-synthetic Polymer: 

    1. Hydrogenated natural rubber, cellulose nitrate, methyl cellulose, etc. are chemically modified polymers.

Based on the types of monomer:

  1. Homopolymer: 

  • A polymer containing a single type of repeat units is called a homopolymer. 

  • e.g., polystyrene. 

  1. Copolymer: 

  • If a polymer is made up of two different monomers then it is called copolymer.

  • e.g., styrene butadiene (SBS) rubber and Sty-co-An. 

Ideal Characters of polymers

  1. It should be inert and compatible with the environment.  

  2. It should be non- toxic and physiologically inert. 

  3. It should be easily administrable.  

  4. It should be easy to fabricate and must be inexpensive.   

  5. It should have good mechanical strength.  

  6. It must have compatibility with most of the drugs. 

  7. It must not adversely affect the rate of release of the drug.   

  8. It must not have tendency to retain in tissue and must be a good biodegradable material. 

Properties Of Polymers

  1. Crystallinity:

  • Partial  alignment of  molecular  chains  is  associated  with the process  of crystallization  of polymers.

  • Dyeing of polymers gets  affected by  crystallinity. 

  • Amorphous form  is  much  more  prone  to  dyeing  as  compared  to  crystalline  form  because  the  dye molecules penetrate much easier through amorphous regions.

  1. Viscosity:

  • Viscosity increases, the sustained drug release is prolonged

  1. Polymer complexes:

  • Polymers provide ample opportunity for the formation of complexes in solution.

  • Such macromolecular reactions are  highly  selective  and  strongly  dependent  on  molecular  size,  conformation  heat  etc. 

  • Biological macromolecules undergo complex reactions, which are often vital to their activity.

  1. Syneresis:

  • The separation of liquid from a swollen gel is known as syneresis

  • This is a form of instability in aqueous and non-aqueous gels. 

  • Separation of a solvent phase is thought to occur because of  the elastic  contraction  of  the polymeric molecules.  

  • In the  swelling  process during gel formation the macromolecules involved become stretched and the elastic forces increase as swelling proceeds

  1. Adsorption of macromolecules:

  • The ability of some macromolecules to adsorb at interfaces is being exploited in suspension and emulsion stabilization. 

  • Gelatin, acacia and proteins adsorb at the interface. 

  • Sometimes such adsorption  is  unwanted,  addition  of albumin to prevent adsorption is now common practice

  1. Bio Adhesiveness of water- soluble polymers:

  • Adhesion between a biological surface and a biological surface and a surface of a hydrophilic polymers, arises from  interactions  between  the  polymer  chains  and  the  macromolecules  on  the  mucosal surface.

  • To achieve maximum  adhesion there  should be  maximum interaction  between  the polymer  chains of  the  bioadhesive and  the mucus.  

  • The charge  on the  molecules  will  be important and for two anionic polymers maximum interaction will occur when they are not charged.  

  • Penetration  and association  pH must  be  balanced.  

  • The adhesive  performance  of polymers can be excellent (e.g. carboxymethylcellulose), good (Carbopal), fair (gelatin) or poor (povidone). 

  1. Polymer dissolution:

  • Polymer  dissolution  in  solvents  is  an  important  area  of  interest  in  polymer  science  and engineering because of its many applications in industry such as membrane science, plastics recycling and drug delivery. 

  • Unlike non-polymeric materials, polymers do  not  dissolve  instantaneously,  and  the  dissolution  is  controlled  by  either  the disentanglement of the polymer chains or by the diffusion of the chains through a boundary layer adjacent to the polymer-solvent interface.

Mechanism Of Drug Release By Polymers


  • The drug release by dissolving polymer is by penetration of dissolution fluid. 

  • In a Sustained or  controlled  drug  delivery  system,  a drug  is  dispersed  (matrix  system)  or  encapsulated (individual drug particles) with  slowly dissolving polymers.  

  •   The rate of penetration of  the dissolution  fluid into the matrix determines  the drug  dissolution and  subsequent release.  

  • The penetration  of dissolution  fluid is, however, dictated  by the  matrix,  porosity,  presence of hydrophobic additives and the wettability of the system and surface of the particle

  • In encapsulated system,  the  coat  thickness  and  its  aqueous  solubility  determine  the  time  required  for dissolution of coat one can formulate a repeat action or sustained release product by using a narrow or a wide spectrum of coated particles of varying thickness, respectively,

Drug release by dissolution controlled mechanism of polymer

  1. Diffusion:

  • Diffusion  occurs  when  the  drug  passes  from  the  polymer  matrix  into  the  external environment.  

  • In a controlled  drug  delivery  system,  drug  is  homogeneously  dispersed  in  a polymer  matrix  (monolithic  matrix  system)  or  drug  (solid,  dilute  solution  or  highly concentrated  solution)  within  a  polymer  matrix  and  surrounded  by  thin  film  (reservoir system). 

  • Diffusion occurs  when the drug passes from the polymer matrix into the external environment.  

  • With the passage of time and continuous drug release, the delivery rate normally decreases in this type of system since the  bioactive agent has to traverse a long distance progressively and thereby requires a longer diffusion time for ultimate delivery of drug(s). 

  • In a swelling controlled drug delivery system, drug release by swelling of polymer followed by diffusion of drug with or without dissolution.

Drug release by diffusion controlled mechanism of polymer.

  1. Dissolution and Diffusion:

  • Drug release by dissolution  of polymer followed  by diffusion of drug.  

  • In controlled  drug delivery systems consist of the drug core enclosed in partially soluble membrane. 

  • Dissolution of part of outer membrane leads to facilitated diffusion of the contained drug through pores in the coating by dissolution and diffusion controlled release mechanism of polymer

  1. Erosion:

  1. The  active  agent  is  contained  in  a  core  surrounded  by  a  bioerodible  rate-controlling membrane. 

  • Such a system combines the attributes of a rate-controlling polymer membrane, which provides a constant rate of drug release from a reservoir-type device, with erodibility, which  results  in  bioerosion  and  makes  surgical  removal  of  the  drug-depleted  device unnecessary.  

  • Because  constancy  of  drug  release  demands  that  the  bioerodible  polymer membrane remain essentially unchanged during the  delivery regime, significant bioerosion must not  occur until after drug delivery has  been completed. 

  • Thus,  polymer capsules will remain in the tissue for varying lengths of time after completion of therapy.

  1. The  active agent  is covalently attached to the polymer backbone and  is released as  its attachment to the backbone cleaves by hydrolysis of bond A. 

  • Because it is not desirable to release active agent molecules  with polymer fragments still attached,  reactivity of bond A should be significantly higher than reactivity of bond B.

Drug release mechanism by erosion.

4. Ion exchange:

  • Drug  release  by  reversible  exchange  of  ions  (in  drug-ion  exchange  resin  complex).  

  • Ion exchange resins are used to sustain the effects of drugs based on the concept that negatively or  positively charged  drug moieties combine  with  appropriate resins  producing  insoluble poly salt resonates. 

  • Where R-SO3-H + and R-NH3+OH- represent cationic and anionic resins,  whereas  H2N-A  and  HOOC-B  depict  basic  and  acidic  drugs  respectively. 

  • Where administered orally resins come in contact HCl with pH 1.2 following reaction takes place.

  •  R-SO3-H+   + H2N-A       → R-SO3- + H3N+ -A 

  • R-N+H3- + HOOC-B        → R-N+H3-OOC-B + H2O 

Applications of Polymers in Drug Delivery System:

  1. Tablets:

  • Tablets are the most commonly used dosage form for pharmaceutical preparations meant to be taken orally. 

  • Release of drugs from the tablet can be controlled by altering the design and content of the formulation.

  • In tablets the polymers are used as a Disintegrants and Binder. 

    • E.g. Starch, cellulose, Alginates, polyvinylpyrrolidone, sodium CMC etc are used as disintegrants. 

  • Polymers  used  as  binders  are  

    • e.g. Starch,  HPMC,  Gelatin,  Alginic  acid, polyvinylpyrrolidone, Sucrose, Ethyl cellulose

  • Polymers are also used to mask the unpleasant taste of the drug and also for enteric coating of tablets 

    • e.g. Shellac and zein. 

  1. Capsules:

  • Capsules are generally composed of gelatin. 

  • The composition of gelatin varies so gelatin is of two types that is hard gelatin and soft gelatin. 

  • Fillers such as MCC and starches are used to fill up the volume in the capsule. 

  • To overcome the problem of aggregation various polymers such as starch and sodium starch glycolate are mixed with capsule containers.

  1. In Parenterals:

  • In Parenteral the various polymers like Methacrylic acid act as an Interferon inductor which induces the interferon in cancer like disease. 

  • Methacrylic acid alkyl amide acts as a plasma expander which increases the plasma level in the body.

  • Some Vaccines are transpired by using polymer because which disintegrate in GIT tract, example Methyl methacrylate

  1. Polymers in Disperse systems:

  • Various  synthetic  and  natural  hydrophilic  polymers  are  extensively  used  to  enhance  the physical stability of pharmaceutical disperse systems. Examples of these include alginates, acacia, carrageenan and xanthan gum, whereas a wide range of synthetic polymers has also been used for this purpose, e.g., cellulose ethers, poly(acrylic acid), PVP and PVA.

  1. Polymers in Gels:

  • Gel systems consist of physical or chemical cross-links between adjusted polymer chains that restrict chain mobility. 

  • Gel has rheological properties

  • Cross-linked gels are most commonly known as hydrogels. 

  • They are also known a  s smart polymers because they show different gelling properties  in  different  environments  of  water.  

  • Most  commonly  used  hydrogels  are  poly (hydroxyethyl  methacrylate),  poly  (methacrylic  acid)  and  poly  (acrylamide).  

  • In pharmaceutical industries cross-linked gels are primarily use for local drug delivery of drugs to skin, oral cavity, vagina and rectum.

  1. Swelling Controlled Release Systems:

  • In many drug delivery systems, the  dimensions of the dosage form will change during the course of drug release due to swelling of the polymer matrix. 

  • Although the mechanism for drug release is diffusion, Examples of systems  that exhibit swelling controlled release are physically crosslinked and chemically crosslinked gels. 

  • In terms of controlled drug release, chemically Crosslinked  hydrogels e.g., poly(hydroxyethyl methacrylate), have been used  to provide controlled drug release from medical devices, whereas swelling controlled physical hydrogels may be  easily manufactured by directly compression of drug with a  hydrophilic polymer, e.g., HPMC. 

  1. Temperature Responsive Drug Release:

  • Some controlled systems for the administration of drugs are developed  that use the temperature as an external stimulus. 

  • The polymers used to obtain such release properties are referred to as thermoresponsive polymeric systems. 

  • Typically, the homo and copolymers of N-substituted acrylic and methacrylate amides [e.g. poly (isopropyl acrylamide)], are used for this purpose. 

  • More specifically, there are two types of  thermoresponsive  polymer  systems  namely  those  that  exhibit  positive  and  negative temperature dependency. 

  • Polymers in the former category display an upper critical solution temperature  below which  polymer  contraction occurs  upon  cooling. 

  • Conversely, negative temperature dependent polymers have a lower critical solution temperature and will contract upon heating above the lower critical solution temperature.

  1. pH Responsive Drug Release:

  • Within the gastrointestinal tract a range of pH values  exist, ranging from about one  in the stomach to  neutrality within  the intestine. 

  • Targeting  drug release  within  certain regions  of  the gastrointestinal  tract as  a  method to enhance drug stability within acidic fluids or to reduce the irritant effects of certain drugs.

    • For  example,  enteric  polymers  have  been  used as  tablet coatings for this purpose, examples of which include cellulose acetate phthalate and cellulose acetate butyrate. 

  • These polymers are insoluble in low pH environments; however  they are soluble  in the  less  acid regions  of  the gastrointestinal  tract. 

  • Following dissolution  of  the enteric  coating,  the  tablet  and  hence  the  drug  will  dissolve,  thereby  facilitating  drug absorption. 

  • Due to  this pH dependent solubility, enteric polymers may be described as pH responsive polymers.

  1. Transdermal drug delivery system:

  • Transdermal systems dependent on rate-controlling membranes are available for the delivery of  nitroglycerin, scopolamine,  oestradiol (estradiol),  fentanyl and other drugs. 

  • The barrier properties of skin  are so variable, however,  that one advantage of a rate-controlling  system  generally  consists  of  a  reservoir,  a  rate-controlling  membrane  and  an adhesive layer. 

  • Diffusion of the active principle through the controlling membrane governs release rate. 

  • The active principle is usually present in suspended form; liquids and gels are used as dispersion media. 

  • In a matrix system the active principle is dispersed in a matrix.  

  • In Transiderm  Nitro,  the rate-  controlling membrane is composed of a poly-ethylene/ vinyl acetate copolymer having a thin adhesive layer  (membrane  type). 

  1. Ocular drug delivery system:

  • Improving the ocular contact time of solutions utilizes the incorporation of polymers into an aqueous  medium  such  as  polyvinyl  alchol  (PVA),  polyvinylpyrrolidone  (PVP), methylcellulose,  carboxymethylcellulose (CMC)  and hydroxypropyl cellulose  (HPC). 

  • The increased solution viscosity reduces the solution drainage. 

  • Ocusert has the drug reservoir as a thin disc  of  pilocarpine-alginate  complex  sandwiched  between  two  transparent  discs  of microporous membrane fabricated from ethylene-vinyl acetate copolymer.

Commonly asked questions.

  1. Define “Polymers. Give their classification, ideal characteristics and applications in pharmaceutical formulations.

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