Natural and Biodegradable polymers.pptx

Natural and Biodegradable polymer.

1. SEMINAR ON BIODEGRADABLE POLYMER & NATURAL POLYMER FACILITATED BY: mr. prakash goudanavar DEPT OF PHARMACEUTICS N.E.T. Pharmacy College PRESENTED BY: Dharmendra chaudhary DEPT OF PHARMACEUTICS N.E.T. Pharmacy College

2. Polymers are very large molecules consisting of many repeating units and formed by a process known as polymerization, which links together small molecules known as monomers. They are also known as macromolecules. The monomers are linked together by covalent bonds. Monomers can be linked together in various ways to give 1. Linear 2. Branched 3. Cross linked polymers Polymers

3. Linear and branched polymers are also known as thermoplastic polymers becauses they can flow when heated thus can be fabricated by the application of heat and pressure they are also soluble in certain solvents. Crossed linked polymers are known as thermosetting polymers as they don’t flow when heat or pressure is applied and hence cannot be fabricated by application of heat and pressure since all the polymer chains are inter connected by covalent cross links , they cannot dissolve and only swell to the extent allowed by crossed linked density

4. Biodegradable polymers are polymer that degrades within the body as a result of natural biological processes, eliminating the need to remove a drug delivery system after release of the active agent has been completed. They are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. Biodegradable Polymers

5. The drug depleted delivery systms used could cause toxicological rxns if retained in the body & removal of this from body was difficult and surgical methods had to be adopted to remove it. These type of polymers have wide range of applications because in non biodegradable polymers, the drug release is controlled by diffusion through polymer phase which depends on molecular weight, solubility of drug & polymer permeability . Therefore drugs which are poorly soluble like proteins having a high a high molecular weights are not suitable candidates for delivery system involving non-biodegradable matrices systems as these can aggregate in the matrix and may lead to clogging of pores for diffusion. Need for Biodegradable polymers

6. Characteristics : It should be inert to tissues and compatible with environment. It should be non- toxic and non –antigenic. It should be biodegradable and should be eliminated from body after its function. It should be soluble and easy to synthesis. It should have good mechanical strength, tensile strength, hydrophilicity & crystallarity .

7. 1.Synthetic polymers a) Polyamides e.g.: Polyamino acids, Polypeptides b) Polyesters e.g.: Poly(glycolide), Poly(D,L-lactide) Poly(D,L-lactide-co-glycolide) Poly( E-caprolactone) Poly(dioxanone ), Poly(hydroxybutyrate) c) Polyanhydride d) Polyorthoester e)Polyphosphazene f)Polyphosphoester e.g.: Polyphosphate, Polyphosphonate, Polyphosphate Common classes and examples of biodegradable polymers

8. 2. Natural polymers a)Polysaccharides e.g.: Dextran , Chitosan Alginate, Starch Hyaluronic acid b)Polypeptides, Proteins e.g.: Collagen, Gelatin , Fibrinogen , Albumin Bovine serum albumin (BSA) Human serum albumin (HSA)

9. BIODEGRADATION ENZYMATIC DEGRADATION COMBINATION HYDROLYSIS BULK EROSION SURFACE EROSION

10. Polymer degradation & erosion Degradation primarily is the process of chain clevage leading to reduction in molecular weight Erosion is the sum of all the processes leading to loss of mass from polymer matrix A polymer can erode without degradation and a polymer can degrade completely without being eroded . Polymer DEGRADATION BULK EROSION SURFACE EROSION rate of water penetration exceeds the rate at which polymer is converted into water soluble materials rate of water penetration is slower than the rate at which polymer is converted into water soluble materials

11. Polymer Degradation by Erosion

12. Steps in polymer degradation: In first Phase water penetrates the bulk of the device & preferentially attacks the chemical bonds in the amorphous phase leading to conversion of long chain polymer into short water soluble fragments & due to this there is change in physical property of polymer matrix. In second Phase there is rapid loss of polymer mass due to enzymatic attack which leads to fragmentation. Polymer erosion : Term polymer erosion is generally used to signify conversion of an initially water insoluble material to water soluble

13. Type 1 erosion: evident with water soluble polymers cross linked to form a 3D structure. This network remains insoluble till the cross links are intact but when placed in aqueous environment erosion occurs by cleavage of cross links or water soluble back bone following which the matrix begins to swell & dissolves Type 2 erosion: occurs with polymers that were earlier water insoluble but converted to water soluble forms by hydrolysis, ionization or protonation of a pendant group Type 3 erosion: occurs in polymers that were of high molecular weight but transformed to small, water soluble molecules via hydrolytic cleavage of labile bonds in the polymer Types of polymer erosion

14. Factors affecting polymer degradation: 1. Hydrophilicity:  hydrophilicity  water  rate 2. Tg :  Tg   water uptake  rate Crystallinity:  crystallinity   water uptake  rate Temperature:  temp  rate Acid or base: rate  porosity (inc. surface area)  rate Presence of drug (may both promote and perclude polymer hydrolysis)

15. poly (glycolide), poly( lactide ), and various copolymers of poly( lactide -co-glycolide) are ubiquitous choice because of their proven safety and lack of toxicity, their wide range of physicochemical properties, and their flexibility to be processed into a variety of physical dosage forms. prepared by anionic ring-opening reaction of highly purified glycolide and lactide monomers, the cyclic dimers of glycolic acid and lactic acid, respectively. Polyesters

16. Homopolymers of polylactide are semicrystaline hence water transport (uptake) to polymer is low and so the degradation rate of polymer is relatively slow (18-24 mnth). In contrast Poly(D,L- lactide ) PLA is amorphous and degrade somewhat faster(12-16 mnth). Polyglycolide despite being semicrystaline degrade faster(2-4mnth) even compared to amorphous PLA bcoz of greater hydrophilicity of glycolide over lactide. Poly(D,L- lactide -co-glycolide) PLG amorphous if glycolide content is 0-70%. Poly(L- lactide -co-glycolide) amorphous when glycolide content is 25-70%. Most rapid degradation (2 mnth) in PLG is copolymer with 50% glycolide content.

17. Biodegradation: Occurs in 2 steps Random hydrolytic cleavage of ester linkage leading to redn in mol.wt . Onset of wt.loss and a change in rate of chain scission. Drug release: Combination of initial leaching/diffusion followed by bioerosion of matrix. Uses: In microparticulate drug delivery.

18. Adv. Of PCL as biodegradable CDDS Slow degradtion rate, suitable for long term(1yr) delivery system Biodegradibility can be increased by copolymerization. High permiability to large no. of drugs. Non-toxic profile. Ability to form compatible blends with many other polymers. Poly- E- caprolactone (PCL)

19. Monomer Synthesized by oxidation of cyclohexane with perchloric acid . Can be blended with cellulose propionate, cellulose acetate butyrate, polylactide , PLG. Biodegradation: Random hydrolytic chain scission of the ester linkage In 2 nd phase, shows decreased rate of chain scission & weight loss due to diffusion & phagocytosis

20. Specially for surface eroding dosage forms. The anhydride linkages of these polymers are, in general, more hydrolytically labile than the polyester bond. In order to achieve a surface-eroding mechanism, polymers are generally prepared from very hydrophobic monomers in order to minimize water penetration into the bulk of the device. By doing this, hydrolysis of the labile anhydride linkages would be restricted to the outer exposed surfaces of the polymer device. Prepared from dicarboxylic acid like adipic acid, sebacic acid(SA), fumaric acid(FA). Degrade only from the surface to maximize control in a heterogeneous manner over the release process without requiring any additives . Degrade more rapidly in basic media then in acidic media. Rate of degradation is function of chain length. Disadvntage : Chemical interaction between drug and polymer. Polyanhydrides

21. Have acid labile linkage in their backbone which facilitates manipulation of hydrolysis rate by means of acidic or basic excipients . Are acid sensitive and are stable in base. Used to fabricate contraceptive steroid bearing bioerodible implants. Prepared by transesterifiacation of diol and co- hydroxy butyric acid. Also prepared by addition of polyols to diketene acetals . Polymer erosion can be accelerated by using diols bearing pendent carboxylic groups(eg.9,10-dihydroxystearic acid ) as comonomers . Polyorthoesters

22. Contain a long chain backbone of alternating phosphorus and nitrogen atoms. Degrade into endogenous N & P compounds hence ideal biodegradable polymers synthesis by rxn of poly( dichlorophosphazene )with organic nucleophiles such as alkoxides,aryloxides , or amines. Can be hydrohilic or hydrophobic. Polymer prodrugs have been prepared in which the drug entity is covalently attached to the polyphosphazene. Polyphosphazenes have been studied for the delivery of proteins, naproxen and colchicine , as well as in periodontal treatments. Made into film and hydrogels . Also in implant s . Polyphosphazenes

23. Generally referred as polyphosphates(P-O-C), polyphosphonates (P-C) or polyphosphites depending on nature of side chain attached to phosphorus. Disadvntage : Cost of synthesis and apparent hydrolytic instability. used as microspheres for delivery of drugs like lidocaine , placitaxel , cisplatin and as a gel for lidocaine , doxorubicin. Polyphosphoesters

24. Natural polymers Also known as biopolymers these have a few advantages like: They are derived from natural source Easily available Relatively cheap Qualified for a number of chemical modifications Natural polymers can be proteins and polysaccharides in chemical origin The natural polymers are subjected to a number of chemical modifications so as to increase the biodegradability. So generally labile functional groups are added to the polymer to enhance the biodegradability.

25. Structural protein which occurs in animal tissues as aligned fibers in skin connective tissue and in bone. Advantages: Easy to isolate & purify Biocompatible & non toxic Well established physiochemical, structural & immunological properties Easy to process Disadvantages : Variability in drug release kinetics, In vivo swelling and poor dimensional stability. Low mechanical strength and elasticity in vivo Chances of triggering antigenic response Tissue irritation Collagen

26. These limitations can be overcome to a certain extent by using collagen shields. These shields are prepared from intact porcine scleral tissues. Collagen is most widely used in case of ocular dosage forms. On application the tear fluid hydrates the shield & it starts to dissolve. This leads to its softening & subsequent compliance to the corneal surface Soluble succinylated collagen insert of gentamycin used as an ocular drug delivery system. Formaldehyde treated and chrome treated films of medroxyprogestsrone for sustained release of the hormone etc.

27. It is a major plasma protein component. It is mostly used to design particulate drug delivery system. advantage include their bioavailability into natural products, easy availability, absence of toxicity & antigenicity . Albumin microspheres have been employed to deliver many drugs including insulin, 1- norgestrel , haematoporphyrin, sulphadiazine, prednisolone, 5- fluorouracil, doxorubicin & mitomysin. Basically albumin microspheres have been exploited for chemotherapy as with them high local drug administration can be achieved for a relatively longer time period. Typically the release pattern of drugs from albumin microspheres is biphasic. The initial burst release is followed by a comparatively slower first order release. Albumin

28. Gelatin: It is a heterogeneous product obtained by irreversible hydrolytic extraction of treated animal collagen. This partial hydrolysis converts the tough fibrous collagen into an unoriented water soluble protein . Gelatin micropellets can be prepared oral controlled delivery of drugs. Gelatin has been employed as a matrix and as a coating material in drug delivery systems . Advantages: Easy availability Low antigen profile Poor binding to drug molecule Low temperature preparation technique that reduces the chances of drug degradation.

29. Fibrinogen: Fibrinogen is a soluable plasma protein having a molecular weight of 340,000. Fibrinogen microspheres can be prepared by emulsification technique followed by thermal denaturation . Drugs like doxorubicin 5- fluro urasil , & adriamysin have been delivered with fibrinogen microspheres.

30. Chitin & Chitosin : Chitin is a linear polycationic polymer of N- acetyl-D –glucosamine. It is highly insoluble in common solvents & has close resemblance to cellulose by having similar solubility profile & low chemical reactivity. The principle industrial source of chitin is shells of shrimp lobsters & crab. Chitosin is a principle derivative of chitin & is obtained by alkaline deacetylation . They are distinguished by their solubility profile in dil. Aq. Acid solns .

31. Pharmaceutical & biomedical applications are: Show antacid & anti ulcer activity Show wound healing properties Show haemostatic & spermicidal property Presence of reactive functional groups & cationic character opens up possibilities for their applications in controlled drug delivery Good biodegradability, biocompatibility, & non toxic Has gel forming ability at low ph. Chitosin has been used as a direct tableting agent.

32. Addition of chitosin to conventional excipients decreases the angle of repose and therby increases the fluidity of powder mixtures It has been used as a diluent binder lubricant and potential disintegrant due to its water uptake property Ulcerogenic drugs like aspirin can be effectively administered with chitosin as the latter has gel forming property at low ph and also has anti ulcer and antacid property Gastric mucosal injury associated with diclofenac sodium can be reduced with chitosin Oral mucoadesive tablets based on chitosin also show immense application potential

33. As it has gel forming property at low ph It can be used for oral sustained drug delivery system Mucoadesive chitosin coated liposomes could improve the oral absorption of insulin. Chitosin has inherent antitumour activity thus chitosin microspheres bearing neoplastic agents are therapeutically promising carriers for treatment of cancer. The film forming capacity of the chitosin can be employed for development of contact lenses. It can be employed in ocular bandage lenses used as protective devices for acutely and chronically traumatized eyes.

34. These are hydrophilic carbohydrates obtained from various species of brown sea weed by the use of alkali. They can be easily fabricated into particulate carriers. They are particularly beneficial as carriers of peptides and other sensitive drugs since particulate carriers can be easily prepared in aqueous solutions at room temperature. Alginate microspheres have been effectively used for oral delivery of vaccines. Alginate

35. It is a polymer of glucose. Obtained by action of bacteriunm Leuconostoc mesenteroides on sucrose. The crude high mol wt dextran is formed is hydrolyzed and fractionated to yeild dextran of desired mol wt. Polymers with mol.wt . below 90,000 rarely show immunogenic rxn . Used in the form of gel for colonic delivery of drugs Dextran

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