logging in or signing up RECENT UPDATES IN SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS aSGuest53779 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1368 Category: Education License: All Rights Reserved Like it (6) Dislike it (0) Added: July 10, 2010 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: Shyam03 (10 month(s) ago) Could you please send me this ppt to vijaykumar20009@gmail.com. Thank you Saving..... Post Reply Close Saving..... Edit Comment Close By: jainabhishek (20 month(s) ago) Nice presentation... Had covered all the basics related to polymers in different formulation. Saving..... Post Reply Close Saving..... Edit Comment Close By: fmypa (22 month(s) ago) Thank you for your generously in making your presentation publicly available. fmypa@aol.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Recent updates in synthetic polymers used in drug delivery systems : Recent updates in synthetic polymers used in drug delivery systems KUSUM SINGH NEELAM SINGH I.T.S. PHARMACY COLLEGE,GHAZIABAD, INDIA CONTENTS : CONTENTS INTRODUCTION DEFINITION CLASSIFICATION PROPERTIES & SELECTION OF SYNTHETIC POLYMERS SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS 2 INTRODUCTION : INTRODUCTION Significant advances have been made in development of various drug delivery devices with the help of polymers. The earliest DDS first introduced in 1970s were based on polymers formed from lactic acid. Today polymeric materials still provides most important avenues of research primarily because of ease of processing & ability of researchers to readily control their chemical & physical properties via. Molecular system. 3 DEFINITION : DEFINITION POLYMERS:- Compounds with high molecular masses formed by combination of large number of simple molecules called as monomers. Prepared by addition / condensation polymerization. In Greek, Poly means many & meros means units/parts. Polymers are of 3 types:- Natural, Semisynthetic, Synthetic. 4 CLASSIFICATION OF SYNTHETIC POLYMERS : CLASSIFICATION OF SYNTHETIC POLYMERS ON THE BASIS OF STRUCTURE BRANCHED CHAIN POLYMERS EXAMPLES:- Low Density Polythene CROSS LINKED POLYMERS EXAMPLES:- Bakelite, MF Resin LINEAR POYMERS EXAMPLES:- PEG, Polyesters 5 Slide 6: CONTD… ON THE BASIS OF DEGRADABILITY OF POLYMERS BIODEGRADABLE POLYMERS NONBIODEGRADABLE POLYMERS ENVIRONMENT RESPONSIVE POLYMERS ELECTRICALLY & CHEMICALLY CONTROLLED POLYMERS THERMOSENSITIVE POLYMERS pH-SENSITIVE POLYMERS 6 Slide 7: SYNTHETIC POLYMER :- 7 Slide 8: ON THE BASIS OF MONOMERIC UNITS CONTD… HOMOPOLYMERS COPOLYMERS GRAFTED COPOLYMERS ALTERNATING COPOLYMERS BLOCK COPOLYMERS RANDOM COPOLYMERS 8 PROPERTIES & SELECTION OFPOLYMERS : PROPERTIES & SELECTION OFPOLYMERS POLYMER IS CHOOSEN ON BASIS OF :- Physicochemical properties Need for biochemical characterization. Chemical composition Micro structural design Surface properties like lubricity, hydrophilicity, smoothness, surface energy 9 PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS : PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS Solubility Viscosity Polymer- Solvent interaction Crystallinity Polymer dissolution Bioadhesivity of Hydrophilic polymer Polymer erosion & Biodegradation 10 SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS SYNTHETIC POLYMERS IN DENDRITIC DRUG DELIVERY SYSTEMS DENDRIMERS- Transport extremely high densities of drug molecules. It is suitable carrier system because:- Their size & structure can be controlled. Encapsulate small drug molecule to form Polymer micelles. Serves as “hubs” onto which large number of drug molecules can attached via covalent bond. 11 Slide 12: PAMAM Dendrimer – Used in gene delivery. It has amine Terminal group which binds to DNA by electrostatic charge. Prepared either as Divergent /Convergent type. StarburstTM PAMAM dendrimer in intact (Polyfect(R)) & fractured form (Superfect®). Fractured form shows better gene expression. Polyethyleneimine(PEI)- To prepare PEI- gene complex. After internalization release of gene complex by endosome occurs due to protonation of internal 3° Nitrogen by endosomal protons which then results in swelling of endosome & ultimately releases DNA. 12 Slide 13: 13 Slide 14: 14 SYNTHETIC POLYMER USED IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMER USED IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS Factors to be considered :- Chain flexibility Low molecular weight Ability to form H-bonding Concentration & swelling of polymers. Synthetic Polymers used as Permeation enhancers:- 15 Slide 16: BIOADHESIVE POLYMERS IN MUCOADHESIVE DRUG DELIVERY SYSTEMS 16 SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS Sustained Release DDS follows 1st order release kinetics. Increased crosslinking of polymers decreases diffusion rate & thus improves sustained release properties of polymers & decreases mucoadhesivity. Synthetic Absorbable Polymers- include homopolymers like PLA, PGA, PCL, Polytrimethylene carbonate, Poly(p-dioxanone) & copolymers like- Poly lactide-co-glycolide, Poly (glycolide-co-trimethylene carbonate). 17 Slide 18: 18 SYNTHETIC POLYMER BASED VECTORS IN GENE THERAPY : SYNTHETIC POLYMER BASED VECTORS IN GENE THERAPY Cationic Polymers of high mol. wt. is used. Synthetic Polymers used :- PAMAM, Poly(4-Vinyl imidazole), PPL-Poly-L-lysine, PDMAEMA. Poly-L-lysine:- Biodegradable, lacks –NH2 gp. with a pKa between 5 & 7 allowing no endosmolysis, resulting in low transgene expression. This drawback requires inclusion of endosmolytic agent like Fusogenic peptide like – Copolymer of Poly-L-lysine with Poly-L-histidine/ L-tryptophan. Polyethyleneimine- Shows efficient transfecting ability without use of fusogenic agent. PEI offers high charge density due to which it offers increased protection against serum nucleases. 19 Slide 20: 20 SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS Properties of synthetic Polymers considered for Opthalamic DDS- Non-Toxic, Biodegradable, Biocompatible, Optically transparent, Do not impede vision, Tolerable, good retention properties, mucoadhesivity. Non-Biodegradable polymeric bioadhesives used as drug delivery systems:- Copolymers based on Vinylpyrrolidone, Methacrylic acid, Polydimethylene- siloxane, Poly (N-isopropyl acrylamide), PAMAM dendrimers. 21 Slide 22: CONTD… 22 SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM : SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM Polymers are the backbone of TDDS. TDDS are fabricated as multilayered polymeric laminates or drug- polymer matrix is sandwiched between two polymeric layers i.e. backing layer & inner polymeric layer which act as adhesive & Rate- controlling membrane. TDDS is formulated either as Matrix form / Reservoir form. 23 Slide 24: IN TDDS POLYMERS ACTS AS MATRIX FORMERS BACKING LAYERS RELEASE LINERS RATE –CONTROLING MEMBRANE PRESSURE- SENSITIVE ADHESIVES (PSAs) 24 Slide 25: MATRIX FORMERS Selected on the basis of:- Release properties Adhesion cohesion balance Physicochemical properties e.g.-Monolithic solid state design is preffered for Passive TDDS Synthetic polymers used- Cross linked PEG network Biocompatible Used for protein drug delivery. b) Acrylic acid matrices Acrylic acid + Plasticizer :- used to make drug- polymer matrix film. Eudragit RLPM, Eudragit S-100, Eudragit E-100, ethyl acetate & MMA 25 Slide 26: c) Polyvinylpyrrolidone Matrix formers with 30% Dibutyl Phthalate to deliver Diltiazem Hydrochloride & Domethacin d) HPMC Hydrophillic, swellable polymer used for Oral Controlled DDS Matrix formers in Propranolol HCl For fast release of drug. 2) RATE CONTROLLING MEMBRANE Ethyl Vinyl Acetate By altering Vinyl Acetate content membrane permeability can be controlled b) Silicone Rubber Biocompatible Highly permeable to steroids Ease of fabrication Low microscopic viscosity & used in Controlled Release devices. 26 Slide 27: c) Poly Urethane Rubbery & increased permeability Two types:- Polyether urethanes & Polyester Urethanes Due to more Biodegradability Polyester Urethanes are more preffered. It is used for Hydrophillic polar drugs. PRESSURE SENSITIVE ADHESIVES Characteristic of visco- elastic material Poly Iso Butylene Formed by cationic polymers b) Poly Acrylates Amorphous, gives water clear color in solution & stable towards ageing & have good mechanical properties. c) Silicones Contains low viscosity Dimethyl siloxane polymer. Silicate Resin + PDMS undergoes condensation to form Silicone PSA 27 Slide 28: 4) BACKING MATERIALS 28 Slide 29: 29 Slide 30: SYNTHETIC POLYMERS USED IN HYDROGEL DRUG DELIVERY SYSTEM HYROGELS:- Three dimensional, water swollen systems. Composed of Hydrophilic polymers. Rendered insoluble due to crosslinking. Synthetic Polymers used in Hydrogel DDS PVA, PE, PEG, PMMA, Polyacrylamide, PEA, PEMA, HEMA, PVP Poly (N-isopropylacrylamide), Poly dimethyl aminoethyl methacrylate, Poly (N- Butyl acrylate), Itaconic acid monoester, HPMA, Poly Ethylene oxide dimethacrylate (PEODM), Poly (2- dimethylamino) ethyl methacrylate (DEAEMA), Poly (2- diethylamino) ethyl methacrylate (DMAEMA) 30 Slide 31: 31 Slide 32: 32 Slide 33: 33 Slide 34: 34 Slide 35: SYNTHETIC POLYMERS USED IN GASTRORETENTIVE DRUG DELIVERY SYSTEMS (GRDDS) GRDDS are Oral controlled DDS. Releases drug prior to Absorption window. Prolongs Drug release rate. Ensures optimal BA. 35 Slide 36: SYNTHETIC POLYMERS USED IN GRDDS- FLOATING SYSTEMS Matrix formers like- Polystyrene, PMMA, Polyacrylates, Polycarbonates, Polycarbophil & Highly swellable gel- forming hydrocolloid like- HEC, HPMC, HPC, Na CMC. They hydrates, swells & maintains density <1 thus, confers buoyancy to dosage form & leads to GRDDS & ↓ PDC fluctuations. 2) BIOADHESIVE/ MUCOADHESIVE SYSTEM 36 Slide 37: 3) SWELLING SYSTEMS Polymer should be swellable, hydrophilic, of appt. mol. Wt. Swelling depends on degree of crosslinking. 37 SYNTHETIC POLYMERS USED IN CONTROLLED DDS : SYNTHETIC POLYMERS USED IN CONTROLLED DDS CRDDS follows Zero- order release Kinetics. Requires swellable polymers which are capable of forming external gel layer controlling drug release. 38 SYNTHETIC POLYMERS USED IN CONTROLLED & TARGETED DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN CONTROLLED & TARGETED DRUG DELIVERY SYSTEMS SYNTHETIC POLYMERS USED IN NANOPARTICLE DRUG DELIVERY SYSTEMS Nanoparticles are sub-micron sized colloidal structures. Ist Nanoparticles were based on Non-Biodegradable polymers like Polyacrylamide, PS, PMMA. Now, Biodegradable polymers like Poly(cyanoacrylates) were used in NP. Synthetic Hydrophobic polymers used in NP- PCL, PLA, PLGA, PS. PMMA, PICA, PBCA, PHCA 39 Slide 40: 40 Slide 41: 41 Slide 42: SYNTHETIC POLYMERS USED IN MICELLAR DRUG DELIVERY SYSTEM Polymeric Micelles are few tens in nm , crosslinked combination of hydrophilic & hydrophobic monomers. Forms shell- like structure , hydrophilic portion forms outer shell & it protects core contents from chemical attacks in aqueous media in which they travels. Drug release occur via polymer degradation. Have low CMC, slow dissociation rate & long retention of loaded drug as compared to surfactant micelle. 42 Slide 43: 43 Slide 44: pH-sensitive Micelle based on titrable groups Synthetic block copolymers containing weak basic group:- Poly(2-Vinyl pyridine)-b-PEO, PEO-DMAEMA, PDMAEMA-b-PDAEMA, PEO-b-DMAEMA-b-DEAEMA, DMAEMA-b-Poly[2-(N-morpholino)ethyl methacrylate. Copolymers containing weak acidic groups :- Poly[sodium-2-(acrylamido)-2-methyl propanesulfonate-b-poly (sodium-6-acryl amido hexanoate) & Poly(sodium-4-styrene sulfonate)-b-Poly(sodium-4-vinyl benzoate) Forms micelle at pH <5 PLLA-b-PEO-b-Polysulfamethoxine- have sulfonamide as acidic gp. AMPHIPHILIC STAR POLYMER Prepared from Ethyl methacrylate, PEG-MA, t-butyl MA For delivery of hydrophobic drug like Progesterone. 44 Slide 45: B) pH-sensitive Polyelectrolyte complexes Formed by electrostatic interaction of two oppositely charged Block copolymer. Examples:- [PEO-b-Poly(L-lysine)] & [PEO-b-Poly(Aspartic acid)] (PEO-b-PMANa) & Poly (N-ethyl-4-vinyl pyridinium bromide) Cationic block copolymer forms complex with Polyanionic biomolecules like DNA & ODNs like PEO-b-Polyspermine which make complex with ODNs. PEO-b-PPO triblock combination for Doxorubicin delivery. 45 POLYMER VESCICLES : POLYMER VESCICLES Microscopic sac that encloses a volume with molecularly thin membrane. The membrane are self- directing assemblies of amphiphilic molecues with dual hydrophobic- hydrophobic characters. 46 Slide 47: SYNTHETIC POLYMERS USED IN LIPOSOME DRUG DELIVERY SYSTEMS Polymer properties to be considered :- Low immunogenic. structural versatility. Improves liposomal stability. Easy to associate with liposome surface. A) pH-Sensitive Polymer –Liposome system pH-sensitive synthetic polymers used:- Poly-L-lysine & Poly (His) – Positively charged at low Ph Interact with negatively charged membranes & promotes fusogenic properties. PAMAM – Shows pH-dependent membrane destabilization & thus used for cytoplasmic gene delivery. N-isopropylacrylamide- Provide Temp-responsive properties. 47 Slide 48: STEALTH LIPOSOMES POLYETHYLENE GLYCOL – Hydrophilic, Flexible ↑ Repulsive forces at surface & thus ↓ interaction & plasma protein adsorption. POLOXAMER- Amphipathic polymer with ABA Block structure. PEO-PPO-PEG POLOXAMINES- Tetrafunctional Block copolymer with four PEO-PPO Blocks joined together by central Ethylene diamine bridge. [(PEO-PPO)2- X- (PPO-PEO)2] [(PEG-PPG)2- X- (PEG-PPG)2] 48 Slide 49: 49 REFERENCES : REFERENCES Remington, “The Science & Practice of Pharmacy” Volume- І , B.I. Publications Pvt. Ltd, Lippincott Williams & Wilkins company. Lachman Leon, Lieberman HA, Kanig J.L, “The Theory & Practice of Industrial Pharmacy”, 3rd edition, Varghese Publication. Banker G.S., Rhodes C.T., “Modern Pharmaceutics”, 4th edition Revised, Informa Health care. Vyas S.P., Khar R.K., “Targeted & Controlled Drug Delivery” CBS Publishers & Distributors Jain N.K., “Pharmaceutical Product Development”, 1st edition, Cbs Publishers & Distributors. 50 Slide 51: Wiseman N, Xiao.H, Cherie. O, “Retention acid system of cationic microparticles & anionic polymers experiments & pilot machine trials”, Tappi Journal, Volume 83 Hoshino Y, Urakani T, Kodama Takashi, Oku Naota, Shea J.K, “ Design of Synthetic Polymer NP that capture & neutralize a toxic peptide”, Wiley Interscience. Heller J, “The use of Polymer is construction of Controlled Release Devices”,National Institute on Drug Abuse Research monograph series. Girish Y, Punitha S, “Polymers in mucoadhesive buccal DDS –A Review”, Int. J. Res. Pharm. Sci. Vol- 1, Issue-2, 170-186, 2010. 51 Slide 52: Jain N.K., “Progress in Controlled & Novel Drug Delivery systems”, 1st edition, CBS Publishers & Distributors Jauhar S.P., “ Modern’s Chemistry”, Modern Publishers Kandavilli S, Nair V, Panchagnula R, “Polymers in Transdermal Drug Delivery Systems”, Pharm. Tech. J. Kshirsagar NA, “Drug Delivery System”, Journal of Pharmacology. Twaites B, Heras C, Alexander C, “Synthetic Polymers as Drugs & Therapeutics”, Journal of material chemistry. Duncan R, “Designing Polymer conjugates as lysosmotropic nanomedicines”, Biochemical society Transaction (2007) Vol 35, Part 1 Elvira C, Gallardo A, Roman J.S., Cifuentes A, “ Covalent Polymer Drug Conjugates”, MDPI 52 Slide 53: THANKS 53 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
RECENT UPDATES IN SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS aSGuest53779 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1368 Category: Education License: All Rights Reserved Like it (6) Dislike it (0) Added: July 10, 2010 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: Shyam03 (10 month(s) ago) Could you please send me this ppt to vijaykumar20009@gmail.com. Thank you Saving..... Post Reply Close Saving..... Edit Comment Close By: jainabhishek (20 month(s) ago) Nice presentation... Had covered all the basics related to polymers in different formulation. Saving..... Post Reply Close Saving..... Edit Comment Close By: fmypa (22 month(s) ago) Thank you for your generously in making your presentation publicly available. fmypa@aol.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Recent updates in synthetic polymers used in drug delivery systems : Recent updates in synthetic polymers used in drug delivery systems KUSUM SINGH NEELAM SINGH I.T.S. PHARMACY COLLEGE,GHAZIABAD, INDIA CONTENTS : CONTENTS INTRODUCTION DEFINITION CLASSIFICATION PROPERTIES & SELECTION OF SYNTHETIC POLYMERS SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS 2 INTRODUCTION : INTRODUCTION Significant advances have been made in development of various drug delivery devices with the help of polymers. The earliest DDS first introduced in 1970s were based on polymers formed from lactic acid. Today polymeric materials still provides most important avenues of research primarily because of ease of processing & ability of researchers to readily control their chemical & physical properties via. Molecular system. 3 DEFINITION : DEFINITION POLYMERS:- Compounds with high molecular masses formed by combination of large number of simple molecules called as monomers. Prepared by addition / condensation polymerization. In Greek, Poly means many & meros means units/parts. Polymers are of 3 types:- Natural, Semisynthetic, Synthetic. 4 CLASSIFICATION OF SYNTHETIC POLYMERS : CLASSIFICATION OF SYNTHETIC POLYMERS ON THE BASIS OF STRUCTURE BRANCHED CHAIN POLYMERS EXAMPLES:- Low Density Polythene CROSS LINKED POLYMERS EXAMPLES:- Bakelite, MF Resin LINEAR POYMERS EXAMPLES:- PEG, Polyesters 5 Slide 6: CONTD… ON THE BASIS OF DEGRADABILITY OF POLYMERS BIODEGRADABLE POLYMERS NONBIODEGRADABLE POLYMERS ENVIRONMENT RESPONSIVE POLYMERS ELECTRICALLY & CHEMICALLY CONTROLLED POLYMERS THERMOSENSITIVE POLYMERS pH-SENSITIVE POLYMERS 6 Slide 7: SYNTHETIC POLYMER :- 7 Slide 8: ON THE BASIS OF MONOMERIC UNITS CONTD… HOMOPOLYMERS COPOLYMERS GRAFTED COPOLYMERS ALTERNATING COPOLYMERS BLOCK COPOLYMERS RANDOM COPOLYMERS 8 PROPERTIES & SELECTION OFPOLYMERS : PROPERTIES & SELECTION OFPOLYMERS POLYMER IS CHOOSEN ON BASIS OF :- Physicochemical properties Need for biochemical characterization. Chemical composition Micro structural design Surface properties like lubricity, hydrophilicity, smoothness, surface energy 9 PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS : PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS Solubility Viscosity Polymer- Solvent interaction Crystallinity Polymer dissolution Bioadhesivity of Hydrophilic polymer Polymer erosion & Biodegradation 10 SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS SYNTHETIC POLYMERS IN DENDRITIC DRUG DELIVERY SYSTEMS DENDRIMERS- Transport extremely high densities of drug molecules. It is suitable carrier system because:- Their size & structure can be controlled. Encapsulate small drug molecule to form Polymer micelles. Serves as “hubs” onto which large number of drug molecules can attached via covalent bond. 11 Slide 12: PAMAM Dendrimer – Used in gene delivery. It has amine Terminal group which binds to DNA by electrostatic charge. Prepared either as Divergent /Convergent type. StarburstTM PAMAM dendrimer in intact (Polyfect(R)) & fractured form (Superfect®). Fractured form shows better gene expression. Polyethyleneimine(PEI)- To prepare PEI- gene complex. After internalization release of gene complex by endosome occurs due to protonation of internal 3° Nitrogen by endosomal protons which then results in swelling of endosome & ultimately releases DNA. 12 Slide 13: 13 Slide 14: 14 SYNTHETIC POLYMER USED IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMER USED IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS Factors to be considered :- Chain flexibility Low molecular weight Ability to form H-bonding Concentration & swelling of polymers. Synthetic Polymers used as Permeation enhancers:- 15 Slide 16: BIOADHESIVE POLYMERS IN MUCOADHESIVE DRUG DELIVERY SYSTEMS 16 SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS Sustained Release DDS follows 1st order release kinetics. Increased crosslinking of polymers decreases diffusion rate & thus improves sustained release properties of polymers & decreases mucoadhesivity. Synthetic Absorbable Polymers- include homopolymers like PLA, PGA, PCL, Polytrimethylene carbonate, Poly(p-dioxanone) & copolymers like- Poly lactide-co-glycolide, Poly (glycolide-co-trimethylene carbonate). 17 Slide 18: 18 SYNTHETIC POLYMER BASED VECTORS IN GENE THERAPY : SYNTHETIC POLYMER BASED VECTORS IN GENE THERAPY Cationic Polymers of high mol. wt. is used. Synthetic Polymers used :- PAMAM, Poly(4-Vinyl imidazole), PPL-Poly-L-lysine, PDMAEMA. Poly-L-lysine:- Biodegradable, lacks –NH2 gp. with a pKa between 5 & 7 allowing no endosmolysis, resulting in low transgene expression. This drawback requires inclusion of endosmolytic agent like Fusogenic peptide like – Copolymer of Poly-L-lysine with Poly-L-histidine/ L-tryptophan. Polyethyleneimine- Shows efficient transfecting ability without use of fusogenic agent. PEI offers high charge density due to which it offers increased protection against serum nucleases. 19 Slide 20: 20 SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS Properties of synthetic Polymers considered for Opthalamic DDS- Non-Toxic, Biodegradable, Biocompatible, Optically transparent, Do not impede vision, Tolerable, good retention properties, mucoadhesivity. Non-Biodegradable polymeric bioadhesives used as drug delivery systems:- Copolymers based on Vinylpyrrolidone, Methacrylic acid, Polydimethylene- siloxane, Poly (N-isopropyl acrylamide), PAMAM dendrimers. 21 Slide 22: CONTD… 22 SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM : SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM Polymers are the backbone of TDDS. TDDS are fabricated as multilayered polymeric laminates or drug- polymer matrix is sandwiched between two polymeric layers i.e. backing layer & inner polymeric layer which act as adhesive & Rate- controlling membrane. TDDS is formulated either as Matrix form / Reservoir form. 23 Slide 24: IN TDDS POLYMERS ACTS AS MATRIX FORMERS BACKING LAYERS RELEASE LINERS RATE –CONTROLING MEMBRANE PRESSURE- SENSITIVE ADHESIVES (PSAs) 24 Slide 25: MATRIX FORMERS Selected on the basis of:- Release properties Adhesion cohesion balance Physicochemical properties e.g.-Monolithic solid state design is preffered for Passive TDDS Synthetic polymers used- Cross linked PEG network Biocompatible Used for protein drug delivery. b) Acrylic acid matrices Acrylic acid + Plasticizer :- used to make drug- polymer matrix film. Eudragit RLPM, Eudragit S-100, Eudragit E-100, ethyl acetate & MMA 25 Slide 26: c) Polyvinylpyrrolidone Matrix formers with 30% Dibutyl Phthalate to deliver Diltiazem Hydrochloride & Domethacin d) HPMC Hydrophillic, swellable polymer used for Oral Controlled DDS Matrix formers in Propranolol HCl For fast release of drug. 2) RATE CONTROLLING MEMBRANE Ethyl Vinyl Acetate By altering Vinyl Acetate content membrane permeability can be controlled b) Silicone Rubber Biocompatible Highly permeable to steroids Ease of fabrication Low microscopic viscosity & used in Controlled Release devices. 26 Slide 27: c) Poly Urethane Rubbery & increased permeability Two types:- Polyether urethanes & Polyester Urethanes Due to more Biodegradability Polyester Urethanes are more preffered. It is used for Hydrophillic polar drugs. PRESSURE SENSITIVE ADHESIVES Characteristic of visco- elastic material Poly Iso Butylene Formed by cationic polymers b) Poly Acrylates Amorphous, gives water clear color in solution & stable towards ageing & have good mechanical properties. c) Silicones Contains low viscosity Dimethyl siloxane polymer. Silicate Resin + PDMS undergoes condensation to form Silicone PSA 27 Slide 28: 4) BACKING MATERIALS 28 Slide 29: 29 Slide 30: SYNTHETIC POLYMERS USED IN HYDROGEL DRUG DELIVERY SYSTEM HYROGELS:- Three dimensional, water swollen systems. Composed of Hydrophilic polymers. Rendered insoluble due to crosslinking. Synthetic Polymers used in Hydrogel DDS PVA, PE, PEG, PMMA, Polyacrylamide, PEA, PEMA, HEMA, PVP Poly (N-isopropylacrylamide), Poly dimethyl aminoethyl methacrylate, Poly (N- Butyl acrylate), Itaconic acid monoester, HPMA, Poly Ethylene oxide dimethacrylate (PEODM), Poly (2- dimethylamino) ethyl methacrylate (DEAEMA), Poly (2- diethylamino) ethyl methacrylate (DMAEMA) 30 Slide 31: 31 Slide 32: 32 Slide 33: 33 Slide 34: 34 Slide 35: SYNTHETIC POLYMERS USED IN GASTRORETENTIVE DRUG DELIVERY SYSTEMS (GRDDS) GRDDS are Oral controlled DDS. Releases drug prior to Absorption window. Prolongs Drug release rate. Ensures optimal BA. 35 Slide 36: SYNTHETIC POLYMERS USED IN GRDDS- FLOATING SYSTEMS Matrix formers like- Polystyrene, PMMA, Polyacrylates, Polycarbonates, Polycarbophil & Highly swellable gel- forming hydrocolloid like- HEC, HPMC, HPC, Na CMC. They hydrates, swells & maintains density <1 thus, confers buoyancy to dosage form & leads to GRDDS & ↓ PDC fluctuations. 2) BIOADHESIVE/ MUCOADHESIVE SYSTEM 36 Slide 37: 3) SWELLING SYSTEMS Polymer should be swellable, hydrophilic, of appt. mol. Wt. Swelling depends on degree of crosslinking. 37 SYNTHETIC POLYMERS USED IN CONTROLLED DDS : SYNTHETIC POLYMERS USED IN CONTROLLED DDS CRDDS follows Zero- order release Kinetics. Requires swellable polymers which are capable of forming external gel layer controlling drug release. 38 SYNTHETIC POLYMERS USED IN CONTROLLED & TARGETED DRUG DELIVERY SYSTEMS : SYNTHETIC POLYMERS USED IN CONTROLLED & TARGETED DRUG DELIVERY SYSTEMS SYNTHETIC POLYMERS USED IN NANOPARTICLE DRUG DELIVERY SYSTEMS Nanoparticles are sub-micron sized colloidal structures. Ist Nanoparticles were based on Non-Biodegradable polymers like Polyacrylamide, PS, PMMA. Now, Biodegradable polymers like Poly(cyanoacrylates) were used in NP. Synthetic Hydrophobic polymers used in NP- PCL, PLA, PLGA, PS. PMMA, PICA, PBCA, PHCA 39 Slide 40: 40 Slide 41: 41 Slide 42: SYNTHETIC POLYMERS USED IN MICELLAR DRUG DELIVERY SYSTEM Polymeric Micelles are few tens in nm , crosslinked combination of hydrophilic & hydrophobic monomers. Forms shell- like structure , hydrophilic portion forms outer shell & it protects core contents from chemical attacks in aqueous media in which they travels. Drug release occur via polymer degradation. Have low CMC, slow dissociation rate & long retention of loaded drug as compared to surfactant micelle. 42 Slide 43: 43 Slide 44: pH-sensitive Micelle based on titrable groups Synthetic block copolymers containing weak basic group:- Poly(2-Vinyl pyridine)-b-PEO, PEO-DMAEMA, PDMAEMA-b-PDAEMA, PEO-b-DMAEMA-b-DEAEMA, DMAEMA-b-Poly[2-(N-morpholino)ethyl methacrylate. Copolymers containing weak acidic groups :- Poly[sodium-2-(acrylamido)-2-methyl propanesulfonate-b-poly (sodium-6-acryl amido hexanoate) & Poly(sodium-4-styrene sulfonate)-b-Poly(sodium-4-vinyl benzoate) Forms micelle at pH <5 PLLA-b-PEO-b-Polysulfamethoxine- have sulfonamide as acidic gp. AMPHIPHILIC STAR POLYMER Prepared from Ethyl methacrylate, PEG-MA, t-butyl MA For delivery of hydrophobic drug like Progesterone. 44 Slide 45: B) pH-sensitive Polyelectrolyte complexes Formed by electrostatic interaction of two oppositely charged Block copolymer. Examples:- [PEO-b-Poly(L-lysine)] & [PEO-b-Poly(Aspartic acid)] (PEO-b-PMANa) & Poly (N-ethyl-4-vinyl pyridinium bromide) Cationic block copolymer forms complex with Polyanionic biomolecules like DNA & ODNs like PEO-b-Polyspermine which make complex with ODNs. PEO-b-PPO triblock combination for Doxorubicin delivery. 45 POLYMER VESCICLES : POLYMER VESCICLES Microscopic sac that encloses a volume with molecularly thin membrane. The membrane are self- directing assemblies of amphiphilic molecues with dual hydrophobic- hydrophobic characters. 46 Slide 47: SYNTHETIC POLYMERS USED IN LIPOSOME DRUG DELIVERY SYSTEMS Polymer properties to be considered :- Low immunogenic. structural versatility. Improves liposomal stability. Easy to associate with liposome surface. A) pH-Sensitive Polymer –Liposome system pH-sensitive synthetic polymers used:- Poly-L-lysine & Poly (His) – Positively charged at low Ph Interact with negatively charged membranes & promotes fusogenic properties. PAMAM – Shows pH-dependent membrane destabilization & thus used for cytoplasmic gene delivery. N-isopropylacrylamide- Provide Temp-responsive properties. 47 Slide 48: STEALTH LIPOSOMES POLYETHYLENE GLYCOL – Hydrophilic, Flexible ↑ Repulsive forces at surface & thus ↓ interaction & plasma protein adsorption. POLOXAMER- Amphipathic polymer with ABA Block structure. PEO-PPO-PEG POLOXAMINES- Tetrafunctional Block copolymer with four PEO-PPO Blocks joined together by central Ethylene diamine bridge. [(PEO-PPO)2- X- (PPO-PEO)2] [(PEG-PPG)2- X- (PEG-PPG)2] 48 Slide 49: 49 REFERENCES : REFERENCES Remington, “The Science & Practice of Pharmacy” Volume- І , B.I. Publications Pvt. Ltd, Lippincott Williams & Wilkins company. Lachman Leon, Lieberman HA, Kanig J.L, “The Theory & Practice of Industrial Pharmacy”, 3rd edition, Varghese Publication. Banker G.S., Rhodes C.T., “Modern Pharmaceutics”, 4th edition Revised, Informa Health care. Vyas S.P., Khar R.K., “Targeted & Controlled Drug Delivery” CBS Publishers & Distributors Jain N.K., “Pharmaceutical Product Development”, 1st edition, Cbs Publishers & Distributors. 50 Slide 51: Wiseman N, Xiao.H, Cherie. O, “Retention acid system of cationic microparticles & anionic polymers experiments & pilot machine trials”, Tappi Journal, Volume 83 Hoshino Y, Urakani T, Kodama Takashi, Oku Naota, Shea J.K, “ Design of Synthetic Polymer NP that capture & neutralize a toxic peptide”, Wiley Interscience. Heller J, “The use of Polymer is construction of Controlled Release Devices”,National Institute on Drug Abuse Research monograph series. Girish Y, Punitha S, “Polymers in mucoadhesive buccal DDS –A Review”, Int. J. Res. Pharm. Sci. Vol- 1, Issue-2, 170-186, 2010. 51 Slide 52: Jain N.K., “Progress in Controlled & Novel Drug Delivery systems”, 1st edition, CBS Publishers & Distributors Jauhar S.P., “ Modern’s Chemistry”, Modern Publishers Kandavilli S, Nair V, Panchagnula R, “Polymers in Transdermal Drug Delivery Systems”, Pharm. Tech. J. Kshirsagar NA, “Drug Delivery System”, Journal of Pharmacology. Twaites B, Heras C, Alexander C, “Synthetic Polymers as Drugs & Therapeutics”, Journal of material chemistry. Duncan R, “Designing Polymer conjugates as lysosmotropic nanomedicines”, Biochemical society Transaction (2007) Vol 35, Part 1 Elvira C, Gallardo A, Roman J.S., Cifuentes A, “ Covalent Polymer Drug Conjugates”, MDPI 52 Slide 53: THANKS 53