Transcript Polymers
INTRODUCTION TO POLYMERS K AU S A R AH M AD K U L L I Y Y AH O F P H AR M AC Y , I I U M H T T P : / / S T A F F . I I U . E D U . M Y / A K A U S A R Physical Pharmacy 2 1 CONTENTS Polymers in drug delivery •Copolymer •Polysaccharides Properties of polymers •Crosslink density •Molecular weight Physical Pharmacy 2 2 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 selfassembly structure analogous to simple surfactants: solubilisation of sparingly-soluble drugs Physical Pharmacy 2 3 POLYMERS IN DELIVERY SYSTEMS: EXAMPLES Polyurethane Polysiloxane/silicone •elasticity •catheter •inert •implants Polyvinylalcohol Polyethylene Polyvinyl pyrrolidone •hydrophilicity & strength •toughness & lack of swelling •suspension capabilities Physical Pharmacy 2 Polymethyl methacrylate •physical strength & transparency 4 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 5 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 6 EXAMPLE OF BLOCK COPOLYMERS Poly(lactic) acid Poly(glycolic) acid Physical Pharmacy 2 7 POLYSACCHARIDES • Mainly due to formation of gels in aqueous solutions • Examples: • carrageenans • alginates • starch Physical Pharmacy 2 8 CHEMICAL STRUCTURE OF SOME POLYSACCHARIDES USED IN DRUG DELIVERY Physical Pharmacy 2 9 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 10 TYPES OF COPOLYMERS These can be further divided into: 1. Alternating 2. Block 3. Graft or branched Physical Pharmacy 2 11 NATURAL POLYMERS • Chemical modification can be carried out to change the properties • Example: Crosslinking Physical Pharmacy 2 12 RIGIDITY In decreasing order: • Plastics • Rubbers • Elastomers Can be related to the glass transition temperature Physical Pharmacy 2 13 STRUCTURE OF POLYMER Linear Branched Crosslinked Thermoset polymer Physical Pharmacy 2 14 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. Physical Pharmacy 2 15 MOLECULAR WEIGHT/TEMPERATURE & POLYMER PROPERTIES From: Florence & Attwood Physical Pharmacy 2 16 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 17 MOLECULAR WEIGHT DETERMINATION Methods that can be used are:1. Chemical analysis 2. Osmotic pressure 3. Light scattering measurement 4. Gel permeation chromatography Physical Pharmacy 2 18 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 19 NUMBER AVERAGE MW Determined by: 1. Osmometry 2. End-group titration 3. Colligative properties Mn nM n i i i Physical Pharmacy 2 20 WEIGHT AVERAGE MW • • Determined from 1. Light scattering 2. Small Angle Neutron Scattering (SANS) 3. Sedimentation velocity [Hiementz] Bias towards larger molecules Mw nM n M 2 i i i Physical Pharmacy 2 i 21 VISCOSITY AVERAGE MW Determined by intrinsic viscosity niM Mv niMi 1 a i Physical Pharmacy 2 1/ a 22 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 Physical Pharmacy 2 23 Z-AVERAGE MW Determined by sedimentation equilibrium Mz nM nM i i Physical Pharmacy 2 3 i 2 i 24 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 25 MOLECULAR WEIGHT DISTRIBUTION Physical Pharmacy 2 26 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 27