Admire Dube, B. Pharm.(Hons)., M. Pharm., PhDadube@medic.uz.ac.zwOffice A62
Physical Pharmacy (PCU101)
12. Polymeric Systems2Reference TextPhysicochemical principles of pharmacy Florence, A.T and Attwood, D.
Other useful textbooks:Pharmaceutics: the science of dosage form design-Aulton, M.E (Ed).Martins physical pharmacy and pharmaceutical sciences. Physical Chemical and Biopharmaceutical Principles Sinko, P.J and Singh, Y (Ed).33Learning objectivesState the properties of polymers and explain their use in pharmaceutical preparations4PolymersDefinition:A substance of high molecular weight made up of repeating units (monomers).Short chains with few monomers (oligomers)Their size, 3D shape, asymmetry and chemical reactivity give polymers unique propertiesPolymer chains can be linear or branched. Or separate linear and branched chains can be joined by cross-linkers.Homo-polymers and co-polymersSources: naturally occurring and synthetic5Polymers
PolymersRead and know structures, properties and uses of common polymers used in pharmaceutics, e.g.Chitosan, dextran, the cellulose derivatives, alginate, gum tragacanth, acacia, carbopol, pectin, polyvinyl alcohol.10PolymersPolymers exist with a range of molecular weights. This is termed polydispersity. E.g. for Chitosan, molecular weight 50-190 000 DaltonsCalculate number average molecular weight or weight average molecular weight:
Degree of polydispersity =
11The individual molecular weights M1, M2,... cannot be determined separately the equationmerely explains the meaning of the valueMn. In light-scattering techniques, larger moleculesproduce greater scattering; thus theweight (or more strictly the mass) rather thanthe number of the molecules is important,giving a weight average molecular weight, Mw:11Polymers (mixtures)
12Representative polymer-polymer phase behaviour with different molecular architectures. Microphase separation (a) results when thermodynamically incompatible linear homopolymers are mixed. The covalent bond between blocks in a diblock copolymer leads to microphase segregation (c). A mixed architecture of linear homopolymers and the corresponding diblock copolymer produces a surfactant-like stabilized intermediate-scale phase separation (b).Representative polymer-polymer phase behaviour with different molecular architectures. Microphaseseparation (a) results when thermodynamically incompatible linear homopolymers are mixed. The covalent bond betweenblocks in a diblock copolymer leads to microphase segregation (c). A mixed architecture of linear homopolymers and thecorresponding diblock copolymer produces a surfactant-like stabilized intermediate-scale phase separation (b).12Polymers (solubility)Rate of solution of a water soluble polymer depends on its Mw. The higher the Mw, the lower the solubility.Greater degree of crystallinity, lower solubility.Solubility of polymers affects viscosity of solutionsWater-soluble polymers have an ability to increase the viscosity of solvents at low concentrations, to swell or change shape in solution, and to adsorb at surfaces.Therefore slow rate of penetration of solvents (dissolution).Use of polymers for controlled drug releaseUse of polymers as suspending agents in formulations (viscosity adjusting agents to prevent fast settling of drug particles in suspensions)13Polymers (solubility)Insoluble polymers or polymers with a low rate of solution are used to form thin films, as film-coating materials, surgical dressings or membranes for dialysis or filtration; or to form matrices for enveloping drugs to control their release properties
14Polymers (viscosity)Viscosity of macromolecules in solution (relative viscosity)
extrapolate to zero concentration = intrinsic viscosity
Viscosity changes with shape, solvent binding and ionization.
15ratio of the viscosity ofthe solution, , to the viscosity of the puresolvent 0:
At maximumionisation they are stretched out owing tomutual charge repulsion and the viscosityincreases. On addition of small counterionsthe effective charge is reduced and the moleculescontract; the viscosity falls as a result.15Polymers (viscosity)16
Polymers (gels)Viscous cross-linked systems of polymers (in solution) are called gels.A gel is a polymersolvent system containing a 3D network of quite stable bonds which are almost unaffected by thermal motion.Polymer is cross-linked, solution cannot occur and the polymer will only swell by imbibition of liquid to form a gel.Swelling decreases as the degree of crosslinking increases.3D network of stable bonds (unaffected by thermal motion)Critical concentration of gelation is required.Features of a gel:increase in viscosity above the gel pointthe appearance of a rubber-like elasticity,at higher polymer concentrations, a yield point stressTypes of gelsType I (irreversible systems with 3D network formed by covalent bonds)Type II (heat reversible. Intermolecular bonds such as hydrogen bonds)17This concentration is determinedby the hydrophilelipophile balance ofthe polymer and the degree of regularity of thestructure, by polymersolvent interaction, bymolecular weight and the by the flexibility ofthe chain: the more flexible the molecule thehigher is the critical gelling concentration.17Polymers (heterogels)Use of block co-polymers (AAA-BBB-AAA-BBB)Place polymer in solution in which only one of the co-polymers is soluble (e.g. A is water soluble, B water insoluble)Produce a heterogel (drug delivery system)Poly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymers, known commercially as Pluronic or poloxamer surfactants, Formation of micelles.
18SyneresisTerm used to describe separation of fluid from a swollen gelA form of instability in aqueous and non-aqueous gelsOccurs as a result of elastic contraction of the polymeric moleculesin the swelling process during gel formation, the macromolecules involved become stretched and the elastic forces increase as swelling proceeds. At equilibrium, the restoring force of the macromolecules is balanced by the swelling forces, determined by the osmotic pressure. If the osmotic pressure decreases, for example on cooling, water may be squeezed out of the gel.19Polymers (complexes)
20Such macromolecular reactions are highly selective and strongly dependent on molecular size and conformationCan also occur in formulations and biological systems (hyaluronic acids and proteoglycans in the intracellular matrix in cartilage)
Polymers (interactions with ions)Ions can bind to polymers inducing gelationFor example calcium and other multivalent cations can bind to alginate inducing gel formationCan be exploited in manufacture of controlled release systemsCan also have dietary significance. Dietary fibre from plants binds calcium in proportion to its uronic acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption.
Polymers (interactions with solvents)22Interact in a more complex fashion than small molecules/solutesGenerally have no saturation solubility (usually dissolves completely or is only swollen by a given liquid)Swelling dependent on cross-linking of polymer. Swelling decreases as degree of cross-linking increasesSwelling is also function of the solubility parameter of the solvent. If polymer is ionic swelling dependent on ionic strength of solution.Increasing ionic strength decreases repulsion between between chains and allows the polymer to shrink.22Polymers (interactions with solvents)23
PolymersCharacteristics important in defining polymers for formulationGlass transition temperature, TgTensile strengthDiffusion coefficientHardness (crystallinity)SolubilityCrystallinity defines several features of polymers: rigidity, fluidity, the resistance to diffusion of small molecules in the polymer, and degradation.In hydrogels Tg can be measured and is a measure of polymer structure, crosslinking density, solvent content and polymersolventinteractions24Polymers (applications)Suspending agents in formulation of suspensions, e.g carboxypolymethylene (carbopol)Film coating of (tablets/granules) e.g. shellac, zein, glyceryl stearates, cellulose acetate phthalateDrug delivery systems (hydrogels, nanoparticles /micellar structures), e.g. chitosan, alginate, poly(lactic)glycolic acidOral, transdermal, intravenous, implants