Introduction to Polymers Physical Pharmacy 2 4/17/2017 Introduction to Polymers Kausar Ahmad Kulliyyah of Pharmacy, IIUM http://staff.iiu.edu.my/akausar Physical Pharmacy 2 KBA

Polymers in drug delivery Physical Pharmacy 2 4/17/2017 Contents Polymers in drug delivery Copolymer Polysaccharides Properties of polymers Crosslink density Molecular weight Physical Pharmacy 2 KBA

Polymers in drug delivery Physical Pharmacy 2 4/17/2017 Polymers in drug delivery use in drug delivery due to Surface activity efficient stabilisers for colloidal drug delivery system Gel forming capacity rheological control Formation of self-assembly structure analogous to simple surfactants: solubilisation of sparingly-soluble drugs Physical Pharmacy 2 KBA

Polymers in delivery systems: Examples Physical Pharmacy 2 4/17/2017 Polymers in delivery systems: Examples Polyurethane elasticity catheter Polysiloxane/silicone inert implants Polymethyl methacrylate physical strength & transparency Polyvinylalcohol hydrophilicity & strength Polyethylene toughness & lack of swelling Polyvinyl pyrrolidone suspension capabilities Physical Pharmacy 2 KBA

BLOCK COPOLYMERS Consisting of block of two or more polymers Physical Pharmacy 2 4/17/2017 BLOCK COPOLYMERS Consisting of block of two or more polymers Example is poly(ethylene oxide)-poly(propylene oxide) block copolymers: H-OCH2CH2)a(OCH2CHCH3)b(OCH2CH2)cOH Physical Pharmacy 2 KBA

ADVANTAGE OF BLOCK COPOLYMERS Physical Pharmacy 2 4/17/2017 ADVANTAGE OF BLOCK COPOLYMERS degradation rate of polymers can be controlled. can obtain controlled drug release protect compound from harsh environment e.g. in stomach – in particular polymers containing poly(lactic) acid or poly(glycolic) acid Physical Pharmacy 2 KBA

EXAMPLE OF BLOCK COPOLYMERS Physical Pharmacy 2 4/17/2017 EXAMPLE OF BLOCK COPOLYMERS Poly(lactic) acid Poly(glycolic) acid Physical Pharmacy 2 KBA

POLYSACCHARIDES Mainly due to formation of gels in aqueous solutions Physical Pharmacy 2 4/17/2017 POLYSACCHARIDES Mainly due to formation of gels in aqueous solutions Examples: carrageenans alginates starch Exercise: List other types. Physical Pharmacy 2 KBA

Chemical Structure of Some Polysaccharides Used in Drug Delivery Physical Pharmacy 2 4/17/2017 Chemical Structure of Some Polysaccharides Used in Drug Delivery Physical Pharmacy 2 KBA

Properties of Polymers Physical Pharmacy 2 4/17/2017 Properties of Polymers High molecular weight Repeating units Exist as linear or branched Can be crosslinked Properties depend on the polymerisation of the monomers Can be divided into homopolymers or copolymers Physical Pharmacy 2 KBA

TYPES OF Copolymers These can be further divided into: Alternating Physical Pharmacy 2 4/17/2017 TYPES OF Copolymers These can be further divided into: Alternating Block Graft or branched Please find out. Physical Pharmacy 2 KBA

Physical Pharmacy 2 4/17/2017 Natural Polymers Chemical modification can be carried out to change the properties Example: Crosslinking Physical Pharmacy 2 KBA

Rigidity In decreasing order: Plastics Rubbers Elastomers Physical Pharmacy 2 4/17/2017 Rigidity In decreasing order: Plastics Rubbers Elastomers Can be related to the glass transition temperature Physical Pharmacy 2 KBA

Structure of polymer Linear Branched Crosslinked Thermoset polymer Physical Pharmacy 2 4/17/2017 Structure of polymer Linear Branched Crosslinked Thermoset polymer Linear polymers are equivalent to long strings which are not tied together. Branched polymers are equivalent to tying the same pieces of string together but without closed loops If you tie closed loops, then you are creating a crosslinked system e.g. pink dashed lines. According to IUPAC recommendation: A thermosetting polymer is a prepolymer in a soft solid or viscous state that changes irreversibly into an infusible, insoluble polymer network by curing. Curing can be induced by the action of heat or suitable radiation, or both. A cured thermosetting polymer is called a thermoset. Physical Pharmacy 2 KBA

Physical Pharmacy 2 4/17/2017 Crosslink Density The extent of crosslinking in a polymer is expressed as the crosslink density As number of crosslinks increases, the glass transition temperature increases. As a coating crosslinks, the glass transition increases. Ueberreiter and Kanig reported that the change in glass transition temperature was directly proportional to crosslink density [K. Ueberreiter, G. Kanig, J. Chem. Phys., 18, 399 (1950)] Vulcanized rubber, developed by Harvey Firestone, and used for automobile tires, is a well known example of a crosslinked polymer. Phenol formaldehyde resins, epoxy resins, amino resins, polyurethanes, unsaturated polyesters are all examples of polymers that can be used for crosslinked systems. Physical Pharmacy 2 KBA

MOLECULAR WEIGHT/TEMPERATURE & POLYMER PROPERTIES Physical Pharmacy 2 4/17/2017 MOLECULAR WEIGHT/TEMPERATURE & POLYMER PROPERTIES From: Florence & Attwood Physical Pharmacy 2 KBA

Physical Pharmacy 2 4/17/2017 Molecular Weight Both natural and synthetic polymers do not have specific molecular weight Molecular weight is normally expressed as an average The range of molecular weight is described by the POLYDISPERSITY Physical Pharmacy 2 KBA

Molecular Weight Determination Physical Pharmacy 2 4/17/2017 Molecular Weight Determination Methods that can be used are:- Chemical analysis Osmotic pressure Light scattering measurement Gel permeation chromatography In size exclusion chromatography, such as gel permeation chromatography, the intrinsic viscosity of a polymer is directly related to the elution time of the polymer. Therefore, by running several monodisperse samples of polymer in a gel permeation chromatograph (GPC), the values of K and a can be determined graphically using a line of best fit. Then the molecular weight and intrinsic viscosity relationship is defined. Also, the molecular weights of two different polymers in a particular solvent can be related using the Mark–Houwink equation when the polymer-solvent systems have the same intrinsic viscosity: Knowing the Mark–Houwink parameters and the molecular weight of one of the polymers allows one to find the molecular weight of the other polymer using a GPC. The GPC sorts the polymer chains by volume and as intrinsic viscosity is related to the volume of the polymer chain, the GPC data is the same for the two different polymers. For example, if the GPC calibration curve is known for polystyrene in toluene, polyethylene in toluene can be run in a GPC and the molecular weight of polyethylene can be found according to the polystyrene calibration curve. Physical Pharmacy 2 KBA

Average MW The averages can be in terms of:- Number Weight Viscosity Physical Pharmacy 2 4/17/2017 Average MW The averages can be in terms of:- Number Weight Viscosity Z (sedimentation) The above depends on the type of analytical method employed Physical Pharmacy 2 KBA

Number Average MW Determined by: Osmometry End-group titration Physical Pharmacy 2 4/17/2017 Number Average MW Determined by: Osmometry End-group titration Colligative properties Physical Pharmacy 2 KBA

Weight Average MW Determined from Light scattering Physical Pharmacy 2 4/17/2017 Weight Average MW Determined from Light scattering Small Angle Neutron Scattering (SANS) Sedimentation velocity [Hiementz] Bias towards larger molecules Light scattering Small Angle Neutron Scattering (SANS) Physical Pharmacy 2 KBA

Viscosity Average MW Determined by intrinsic viscosity Physical Pharmacy 2 4/17/2017 Viscosity Average MW Determined by intrinsic viscosity intrinsic viscosity Physical Pharmacy 2 KBA

Mark-Houwink Equation Physical Pharmacy 2 4/17/2017 Mark-Houwink Equation h = KMva ‘K’ and ‘a’ are the Mark-Houwink parameters and depend on polymer-solvent characteristics. rigid rods, a=2. hard sphere, a=0. good solvent, a=0.8 Mark–Houwink equation The equation describing the dependence of the intrinsic viscosity of a polymer on its relative molecular mass (molecular weight) and having the form: [η] = K × Ma where [η] is the intrinsic viscosity, K and a are constants the values of which depend on the nature of the polymer and solvent as well as on temperature Note: The use of this equation with the relative molecular mass (molecular weight) is recommended, rather than with molar mass (which has the dimension of mass divided by amount of substance), since in the latter case the constant K assumes awkward and variable dimensions owing to the fractional and variable nature of the exponent a. Source: IUPAC Compendium of Chemical Terminology 2nd Edition (1997) Physical Pharmacy 2 KBA

Z-Average MW Determined by sedimentation equilibrium Physical Pharmacy 2 4/17/2017 Z-Average MW Determined by sedimentation equilibrium Physical Pharmacy 2 KBA

Polydispersity Mw/Mn > 1 Physical Pharmacy 2 4/17/2017 Polydispersity The ratio of Mw/Mn is the degree of polydispersity Mw/Mn > 1 The smaller the ratio, the narrower is the distribution in molecular weight of the polymer Physical Pharmacy 2 KBA

MOLECULAR WEIGHT DISTRIBUTION Physical Pharmacy 2 4/17/2017 MOLECULAR WEIGHT DISTRIBUTION Physical Pharmacy 2 KBA

Physical Pharmacy 2 4/17/2017 References Aulton, M. E. (1988). Pharmaceutics: The Science of dosage form design. London: Churchill Livingstone. Wise, D. L. (2000). Handbook of Pharmaceutical Controlled Release Technology. New York: Marcel Dekker. Chasin, M & Langer, R (1990). Biodegradable polymers as drug delivery systems. New York: Marcel Dekker. Vyas, S. P & Khar, R. K. (2002). Targeted and controlled drug delivery. New Delhi: CBS. Physical Pharmacy 2 KBA