Biodegradable polymers....,

Views:
 
Category: Entertainment
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

BIODEGRADABLE POLYMERS: CHEMISTRY,DEGRADATION,APPLICATIONS:

BIODEGRADABLE POLYMERS : CHEMISTRY,DEGRADATION,APPLICATIONS

CONTENT:

CONTENT Introduction Rationale Types Degradation Drug-polymer matrix Application

BIODEGRADABLE POLYMER:

BIODEGRADABLE POLYMER POLYMERS A polymer is a substance composed of molecules with large molecular mass consisting of repeating structural units , or monomers , connected by covalent chemical bonds TYPES Water Soluble Polymers Biodegradable Polymers Non-biodegradable polymers BIODEGRADABLE POLYMERS Material with ability of functioning for a temporary period and subsequently degrade, under a controlled mechanism, in to product easily eliminated in body metabolism pathway

RATIONALE:

RATIONALE The growth of biotechnology has led to the identification of many potent and powerful protein and gene based macromolecular drug Poor bioavailability through oral route & frequent parenteral injections be performed to maintain treatment efficacy Attempts were made to prolonged action parenteral dosage forms preserving benefits & avoiding risk of constant I.V. infusion Degradable & non-degradable delivery systems Biodegradable polymers get degrades in the body to biological inert & compatible material

Biodegradable Polymers Used for Medical Applications:

Biodegradable Polymers Used for Medical Applications I.NATURAL POLYMERS a.Animal Proteins Albumin Fibrin Poly(lactic acid) Gelatin Fibrinogen b.Animal Polysaccharides Chitin Chitosan Hyaluronic’s c.Plant polysaccharides Starch Dextran Dextrin Alginic acid II.SYNTHETIC POLYMERS Animal proteins Poly(lactic/glycolic acid) b.Animal polysaccharides Poly( β hydroxy butyric acid) Poly anhydride poly(εcaprolactone) c.Plant polysaccharides Poly(orthoesters) Poly alkyl cyanoacrylate

FACTORS AFFECTING POLYMER SELECTION:

FACTORS AFFECTING POLYMER SELECTION Variety of polymer properties to be considered when selecting a biodegradable polymer Regulatory & toxicology status Monomer or copolymer composition Molecular weight Molecular architecture Linear polymers Branched polymer Cross linked network Tacticity Isotactic syndiotactic Atactic Morphology Amorphous Semi crystalline Crystalline Thermal transition temperature Ionization Side chain Main chain end groups

WHAT IS POLYMER DEGRADATION?:

WHAT IS POLYMER DEGRADATION? Degradation “ An irreversible process leading to a significant change of the structure of a material, typically characterized by a loss of properties, such as integrity, molecular weight, structure or mechanical strength.” Biodegradation “ gradual breakdown of a material by a specific biologic activity.” Degradation may takes place by variety of mechanisms ,but it generally relies on two main types : Degradation by Chemical changes Degradation by Erosion

CHEMICAL DEGRADATION:

CHEMICAL DEGRADATION Chemical changes occurs in polymers which includes cleavage of covalent bonds or ionization or protonation either along the back bone or side chains of polymers Chemical degradation leads to change in molecular weight or solubility of polymer Biodegradable polymer which undergoes chemical degradation through random hydrolysis of covalent bond is widely studied

DEGRADATION BY EROSION:

DEGRADATION BY EROSION Degradation by erosion normally takes place in devices that are prepared from soluble polymer The device erodes as water is absorbed in to the system causing chain to hydrate, swells, disintegrate and ultimately dissolve from the dosage form Degradation by erosion results in weight loss of polymer device Erosion mechanism can be described by two means a. Chemical mean b. Physical mean

CHEMICAL EROSION MECHANISM:

CHEMICAL EROSION MECHANISM Can be described by 3 mechanisms TYPE POLYMER MOLE. WEIGHT FIGURE MECH-1 For water soluble polymer Increase in MW MECH-2 For water insoluble polymer with side group No change in MW MECH-3 For water insoluble polymer with labile bond Decrease in MW

PHYSICAL EROSION MECHANISM:

PHYSICAL EROSION MECHANISM ( a) Bulk-eroding system Bulk degradation ( PLA,PGA,PLGA, PCL ) Degradation takes place throughout the whole of the sample Ingress of water is faster than the rate of degradation (b) Surface-eroding system Surface erosion ( poly(ortho)esters and polyanhydrides ) Sample is eroded from the surface Mass loss is faster than the ingress of water into the bulk

POLYMER DEGRADATION BY EROSION :

POLYMER DEGRADATION BY EROSION

DEGRADATION CAN BE DEVIDED :

DEGRADATION CAN BE DEVIDED In to 2 main phases PHASE I Water penetrates the bulk of the device and attacks the chemical bonds in the amorphous phase leading to conversion of long polymer chains into shorter water soluble fragments Their occurs a reduction in molecular weight but which not lead to change in physical properties PHASE II There is a rapid loss of polymer mass due to enzymatic attack and fragment metabolization

Factors That Accelerate Polymer Degradation :

Factors That Accelerate Polymer Degradation More hydrophilic backbone More hydrophilic endgroups. More reactive hydrolytic groups in the backbone. Less crystallinity. More porosity. Smaller device size.

Methods of Studying Polymer Degradation:

Methods of Studying Polymer Degradation Morphological changes (swelling, deformation, bubbling, disappearance…) Weight lose Thermal behavior changes Differential Scanning Calorimetry (DSC) Molecular weight changes Size exclusion chromatography (SEC) Gel permeation chromatography (GPC) mass spectroscopy Change in chemistry Infrared spectroscopy (IR) Nuclear Magnetic Resonance Spectroscopy (NMR)

FORMATION OF DRUG-POLYMER MATRIX:

FORMATION OF DRUG-POLYMER MATRIX Molding (formation of drug matrix) compression molding melt molding solvent casting

COMPRESSION MOLDING:

COMPRESSION MOLDING Polymer and drug particles are milled to a particle size range of 90 to 150 µm Drug / Polymer mix is compressed at ~30,000 psi Formation of some types of tablet / matrix

MELT MOLDING :

MELT MOLDING Polymer is heated to ~10°C above it melting point ( T m ) to form a viscous liquid Mix drug into the polymer melt Shaped by injection molding Advantages More uniform distribution of drug in polymer Wide range of shapes possible Disadvantages Thermal instability of drugs (heat inactivation) Drug / polymer interaction at high temperature Cost

SOLVENT CASTING:

SOLVENT CASTING Co-dissolve drug and polymer in an organic solvent Pour the drug / polymer solution into a mold chilled under dry ice Allow solvent to evaporate Formation of a drug-polymer matrix Advantages Simplicity Suitable for heat sensitive drugs Disadvantages Possible non-uniform drug distribution Proper solvents for drugs and polymers Fragility of the system Unwanted matrix porosity

DRUG RELEASE PATTERN:

DRUG RELEASE PATTERN Drug-polymer bond is cleaved first Initial cleavage of side-chain The polymer is disintegrated firtst

Medical Applications of Biodegradable Polymers:

Medical Applications of Biodegradable Polymers Wound management Sutures Surgical meshes Orthopedic devices Rods Screws Staples Clips Adhesives Ligaments pins Tissue engineering Dental applications Guided tissue regeneration Membrane Void filler following tooth extraction Cardiovascular applications Stents Intestinal applications Anastomosis rings Drug delivery system

APPLICATION: AS A DRUG DELIVERY SYSTEM:

APPLICATION: AS A DRUG DELIVERY SYSTEM Eg: Biopolymer for release of interleukin-2 for treatment of cancer Objective - To develop a means of locally delivering immunostimulatory protein in to tumors in order to enhance the immune response to these tumors Active agents – Interleukin-2 (IL-2) Polymer used – Poly (Lactic-co-glycolic acid) (PLGA) Result - Using only one long acting dose controlled release for 2 to 3 weeks are achieved Procedure - PLGA with IL-2 Homogeneous mixture of Drug and polymer Rotated on a ball meal for 24 hrs at 60 RPM Mixture was extruded under Pressure Matrix were ground and screened To less than 180 ug

APPLICATION: AS A DRUG DELIVERY SYSTEM:

APPLICATION: AS A DRUG DELIVERY SYSTEM Eg: Biodegradable microspheres containing Naltrexone Objective- To improve patient compliance Active drug – Naltrexone Polymer - Poly (L-Lactic acid) Method - Solvent Evaporation Result – Desired drug release rate could be obtained by varying the compression force or amount of drug loading for eg : Smaller size and highly drug loaded microspheres show faster release Procedure: - PLA +Methylene chloride Naltrexone In aqueous phase solution Containing 0.5% w/v PVA Stirred to evaporate solvent Filtered and dried

APPLICATION: AS OCUSERTS:

APPLICATION: AS OCUSERTS Eg : Biodegradable polymer matrix ocuserts of Diclofenac sodium Purpose - Conventional ocular dosage forms have major disadvantage like unpredictable doses therefore attempt is made to prepare ocuserts Drug material - Diclofenac sodium Polymer - Poly( ε - caprolactone) Ε - caprolactone is preferred over poly lactic acid or poly glycolic acid because it degrades slowly and does not generate an acid environment Result : In-vitro:-A steady state release of drug was observed initially up to 7 hrs. and it decrease in later stage In-vivo:- The In-vivo studies showed about 40% of drug release from dosage form after 10 hrs

APPLICATION:IMMOBILIZATION OF ENZYME:

APPLICATION:IMMOBILIZATION OF ENZYME Enzyme supplementation is done in enzyme deficiency by Enzyme immobilization technique ADVANTAGES Heat sensitive enzymes are protected by attachment to inert polymer support Easy for isolation, purification and recovery of active enzymes from reaction mixture Economic process Polymers used :- Polysaccharides, Polyvinyl alcohol, poly hydroxy ethyl methacrylate (PHEMA) Poly (bis (phenoxy)- phosphazene polymer is used for immobilization of enzymes

APPLICATION: AS IMPLANTABLE DELIVERY SYSTEM Eg: IMPLANT IN FRACTURE OF BONE :

APPLICATION: AS IMPLANTABLE DELIVERY SYSTEM Eg: IMPLANT IN FRACTURE OF BONE Biodegradable polymers are preferable over non-degradable Biodegradable polymers degrade at slow rate that enables slow transfer of the load to healing bone BONE + PLATE BONE PLATE Time Mechanical Strength Degradable Polymer Plate

APPLICATIONS:

APPLICATIONS POLYMER DRUG RESULT ALBUMIN Norgesterone, Progesterone Intra arterial delivery to tumors HAEMOGLOBIN Adriamycin Shows retarded release of drug FIBRINOGEN Doxorubicin Sustain the action GELATIN 5 fluro-uracil Targeting drug delivery POLY(AMIDE) L- asparginase To suppress the growth of tumors POLY ( ACRILAMIDE) L- asparginase In acute leukemia

APPLICATIONS:

APPLICATIONS POLYMER DRUG RESULT POLY (AMINO ACIDS) cyclophospheide Suppressed tumor growth in mice POLY (LACTIC ACID)/ POLY (LACTIDE-CO-GLYCOLIDE) Contraceptive drugs Prednisolone Testosterone Ampicillin Sulphadiazine Prolonged action It shows faster release in vivo For controlled released Sustain release for 2 weeks Release for 3 weeks

REFRENCES:

REFRENCES Swarbrick, James. C. Boylan, “ Encyclopedia of pharmaceutical technology” ,2 nd edition, Vol -I,136 Ram Pradhan, Shivprakash, Yamini Shah, Mukesh Gohel, Dushyant Shah, “ Biodegradable polymer research: an overview” , Indian Drugs 33(8) ,374 S. Narasimha Murthy, “ Biodegaradable Polymer Matrix Based Occuserts of Diclofenac Sodium”, Indian Drugs 34(6), 336 N. Venkatesan, Anurag Sood, Ranjit Singh and Suresh P. Vyas, “ biodegradable polymers as Micro particulate drug carriers”, Indian Drugs 32(11),520 Marc Chasin, Robert Langer, “ Biodegradable polymer as drug Delivery System ”, Vol-45 Agis Kydonieus, “ Treatise on Controlled Drug Delivery ”, Marcel Dekker, 199 Joseph R. Robinson, Vincent H. L. Leen. “ Controlled Drug Delivery ,Fundamentals and Applications ”, 2 nd ,edition, 507 V. R. Govariker, N. V. Viswanathan, Jaydev Sreedhar, “ Polymer Science ”, 263

REFRENCES:

REFRENCES http://www.cpia.ca/anti-litter/pdf/BIODEGRADEABLE%20POLYMERS%20A%20REVIEW%2024%20Nov.%202000.%20Final.PDF http://www.rapra.net/consultancy/biopolymers.asp http://www.devicelink.com/mpb/archive/97/11/003.html http://www.devicelink.com/mpb/archive/97/11/003.html http://averousl.free.fr/fichiers/Biodegradable%20Polymers%20Past,%20Present,%20and%20Future%20(Eng).pdf

authorStream Live Help