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Edit Comment Close Premium member Presentation Transcript Polymer properties and characterization : Polymer properties and characterization Keerthi priya overview : overview Introduction Definitions Characters of ideal polymers Polymer properties Types of polymers Degradation of polymers Characterization of polymers Applications of polymers in pharmaceutical industry Introduction : Introduction Polymers are substances of high molecular weight made up of repeating monomer units. Monomers are long chains of covalently bonded carbon atoms The monomer units can be linked together to generate linear polymers, branched polymers or cross linked polymers. The properties of polymers depend on their size, shape and three dimensional structure Process by which the monomer molecules are linked to form a polymer molecule is called polymerization. Introduction : Introduction Polymers are used widely in pharmaceutical systems as adjuvants, suspending and emulsifying agents, flocculating agents, adhesives, packing and coating materials, increasingly as components of controlled and site specific drug delivery systems. Linear polymers : Linear polymers Linear polymers act as thermoplastic materials as they flow on heating and there by permitting fabrication by application of heat and pressure, they also show solubility in certain solvents. Cross linked polymers : Cross linked polymers Are also known as thermosetting materials, they do not flow on heating, they cannot dissolve but only swell. Extensive cross linking leads to a three dimensional and often insoluble polymer network. Slide 7: Polymers in which monomeric units are identical are called homopolymers Those formed from more than one monomer are called as copolymers Copolymers may be described as Alternating copolymers Block copolymers Graft copolymers The size of the polymer molecule is decided by the number of repeated units present in it. This number denotes the degree of polymerization. : The size of the polymer molecule is decided by the number of repeated units present in it. This number denotes the degree of polymerization. Characters of ideal polymer system : Characters of ideal polymer system Inert and compatible with the environment Non-toxic Easily administered Easy and inexpensive to fabricate Should have good mechanical strength Criteria followed in polymer selection : Criteria followed in polymer selection Polymer chosen as potential drug carrier must exhibit certain properties like: The polymer must be soluble and easy to synthesize. It must have finite molecular weight and narrow distribution. It must provide drug attachments or release sites for possibility of incorporation of drug polymer linkage. The polymer should be compatible with the biological environment i.e., should be a) non-toxic b) non-antigenic It should be biodegradable or eliminated from the organisms after the fulfillment of its function. Polymer properties : Polymer properties Molecular weight and molecular weight distribution Polymer hydrophobicity Glass transition temperature crystallinity Molecular weight and molecular weight distribution : Molecular weight and molecular weight distribution A knowledge of molecular weight and molecular weight distribution is important because there is a definite relationship between polymer molecular weight and polymer properties. At very low molecular weight polymer has low mechanical properties. Solubility of polymer decreases with increase in molecular weight. Polymer hydrophobicity : Polymer hydrophobicity When a polymer is placed in an aqueous environment, it will gradually absorb water, and the amount of absorbed water is determined by the polymer structure. According to the nature of polymer-water interactions, polymers can be broadly classified into Hydrophobic polymers Hydrophilic polymers Water soluble polymers Hydrophobic polymers : Hydrophobic polymers These polymers are essentially water impermeable, when placed in aqueous environment will absorb very little water Clearly there is no fixed value for the amount of absorbed water below which a polymer is hydrophobic and above which it is hydrophilic but for purpose of this classification the amount of water should be less than 5% wt Causes for hydrophobicity of polymer are Chain stiffness High degree of crystallinity Presence of high hydrophobic groups where C-H bonds have been replaced by C-F bonds. Hydrophilic polymers : Hydrophilic polymers These are polymers that absord more than 5%wt water Hydrophilic nature is due to Chain flexibility Absence of crystallinity Low molecular weight Low cross linking density Presence of Amino, carboxyl and Hydroxyl groups. Water soluble polymers : Water soluble polymers Freely soluble in water Examples of such polymers Poly vinyl alcohols Poly acrylic acid Poly N-vinyl pyrrolidine Poly acrylamide Poly ethylene oxide Glass transition temperature : Glass transition temperature At low temperatures all amorphous polymers exist in a glassy state, and while in glassy state polymers are characterized by their hardness, stiffness and brittleness. As the temperature is raised, polymers undergo a transition, known as glass transition temperature Tg, where they change from glass to a rubbery elastomer (or) flexible plastic. In designing a controlled release formulation, it must be known whether the polymer is above or below the glass transition temperature. The polymers above Tg are favorable for controlled release formulations because Due to the formation of polymer chains Due to formation of strong intermolecular interaction and there by controll release of drugs. Crystallinity : Crystallinity Polymers that have a regular structure are able to achieve a regular packing of chains and crystallize Crystallization results in regular packing of molecules or ions into a three-dimensional lattice. Enhancement of crystallinity results in decrease in polymer permeability Crystalline regions are essentially impermeable to water, so the rate of polymer hydrolysis in crystalline regions is significantly reduced. Types of polymers : Types of polymers Polymers have been broadly classified as Natural polymers A) polysaccharides- Dextran, chitosan, alginate, starch, hyaluronic acid B) poly peptides/ proteins – collagen, gelatin, bovine serum albumin, human serum albumin. Synthetic polymers Polyesters, polyurethanes, polyamides, polycarbonates, polysiloxanes, polyoetins, polyvinyl compounds Slide 20: Polymers can also be classified on the basis of their interaction with water into: Biodegradable polymers hydrogels Biodegradable polymers as drug carriers : Biodegradable polymers as drug carriers Polymers first developed in the search of biodegradable suture materials, have proven to be useful and successful for long term drug delivery applications Biodegradable polymers are highly desirable in these situations because they degrade in the body to biologically inert and compatible molecules / compatible with body environment. By incorporating drug in biodegradable polymers , dosage forms that release the drug for a prolonged period can be prepared in variety of shapes and sizes Biodegradable polymers offer a novel approach for developing sustained release drug delivery systems that are simple and convenient to patient Degradation of polymers : Degradation of polymers Degradation may take place by variety of mechanisms: 1)Erosion of polymer 2)Chemical changes of polymer Degradation by erosion Takes place in formulations that are prepared from soluble polymers The formulation erodes as it absorbs water, causing the polymer chains to hydrate, swell, disentangle, and ultimately dissolve away from dosage form. Degradation by chemical changes of polymer : Degradation by chemical changes of polymer Biodegradable polymers include those which undergo chemical degradation through random hydrolysis of the covalent bonds constituting the back bone of polymer chain. Random chain scission results in a reduction in the molecular weight of the polymer, polymer chains become progressively shorter, the degradation process proceeds until polymer fragments degraded to soluble oligomers or individual monomers hydrogels : hydrogels Hydrogels are three dimensional hydrophilic polymer network capable of swelling in water or biological fluids and retaining a large amounts of fluids in the swollen state. Hydrogels can be prepared by a wide variety of materials , different monomers-natural origin of collagen, chitosan and hyaluronic acid. Hydrogels are called as stimuli responsive drug delivery systems, because of their excellent capacity of absorbing water and swelling and permeability characters that enables them to undergo structural changes in response to different physical, chemical or biological stimuli and release. Characterization of polymers : Characterization of polymers Polymer composition copolymerization Structure-property relationships Molecular weight Side-chain substitution Polymer composition : Polymer composition polymers are characterized by percent weight of functional group attached to the backbone. The other two modes used for characterization of polymer are: the degree of substitutional (DS) per anhydroglucose or total molar substitution (MS) per anhydroglucose residue. These three modes of characterization are interchangeable. Structure- property relationship : Structure- property relationship Quantitative structure-property relationships are studied to enable the design of drug molecules with optimal therapeutic efficacy. This include the impact of molecular weight, substitution, and copolymerization on solution, gel, mechanical, and thermal properties. Molecular weight effects Many polymer properties are moleculer weight dependent, including solution and melt viscosity, glass transition temperatures, mechanical properties, and gel strength. Slide 29: Effect of molecular weight on solution viscosity: solution viscosity is proportional to polymer molecular weight. (Mark-Houwink equation). η= KMa where: η is the specific viscosity M is the average molecular weight K and a are polymer, solvent. Average molecular weight can be measured by, light scattering and ultra-centrifugation based methods. Slide 30: Effect of molecular weight on mechanical and thermoplastic properties: Mechanical strength of films: for films, an increase in molecular weight tends to increase film tensile strength, elongation and flexibility. This can be explained as longer polymer chains exhibit greater flexibility. Mechanical strength of tablets: For directly compressed tablets, lower polymer moleculer weight therefore results in less post ejection elastic recovery, and greater permanent deformation. For ex: Low moleculer weight HPC grades have been reported to yield stronger tablets than high moleculer weight HPC, due to greater plasticity and lower post-compaction ejection. Side-chain effects : Side-chain effects Effect of side chain structure on polymer solubility: Substitution of less polar groups for hydrogens or hydroxyls on a polymer chain leads to reduction in crystallinity and reduction in melting points. Effect of side chain structure on mechanical properties The nature of side chain substituent type significantly impacts mechanical and thermoplastic properties. HPC and ethyl cellulose re significantly more thermoplastic than HPMC and HEC The compactibility of matrix forming cellulose ethers has been reported to increase in the following rank order: HEC‹HPMC‹HPC. copolymerization : copolymerization Thermal properties of copolymers When the monomers of two crystalline homopolymers are combined, the degree of crystallinity and the melting point are usually depressed. Mechanical properties of copolymers As a co- monomer is added to a crystalline polymer, crystallinity, Tg, and Tm are usually decreased, with a resultant increase in copolymer plasticity and flexibility. Therefore, copolymers are frequently better film formers and tablet-binders than the intial homopolymer. Applications of polymers in pharmaceutical industry : Applications of polymers in pharmaceutical industry Cellulose acetate phthalate, HPMC are used for enteric coating of tablets Cellulose derivatives zein, shellac, polyvinyl alcohol, polyethylene are used for preparation of transdermal patches Polymers are useful as elastic closures or strong packing films or tough plastic containers Hydroxy propyl cellulose, methyl cellulose, polyvinyl alcohol are used as suspending agents Acacia, tragacanth, guargum are used as emulsifying agents Slide 34: Carbopol and sodium carboxy methyl cellulose were used as mucoadhesive polymers Acacia, methylcellulose, starch, PVP are used as binders Polymers used as wound dressing Eg: synthaderm- polyurethane Water soluble polymers such as HPC, PEG, povidone, sodium CMC are used to enhance the solubility of insoluble drugs. conclusion : conclusion Polymeric materials have a pre-eminent position among excipients, as they form the backbone of modern pharmaceutical practice and modified release technologies in particular. Structure property relation ship of polymers is particularly important in the context of current industry focus on ‘Quality by design', and the fact that polymeric materials frequently comprise a significantly greater proportion of the modern dosage form than does the drug . Looking to the future it is clear that polymers will continue to be a tool in the development of controlled release dosage forms. Slide 36: Thank you for listening me……… You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.