Polymers

In AAABBBAAA type block copolymer

11 In AAABBBAAA type block copolymer, A is water soluble and B is water-insoluble, insoluble parts will tend to aggregate. Aqueous solutions of Poly(oxyethylene)-poly(oxypropylene)- poly(oxyethylene)(PEO-PPO-PEO) block copolymers, known *as Pluronic® or Polaxamer, exhibit phase transitions from solution to gel above the CMC.* CH3 HOCH2CH2OxCHOy CH2CH2OH Chemical Structure of poly(ethylene oxide-co-propylene oxide-co- polyethylene oxide) (PEO-PPO-PEO) (Pluronic or Poloxamer) *Hydrophobic drugs can be entrapped in the core of block copolymer micelles and transported at conc. that exceed their water solubility*

BIODEGRADABLITY AND BIOCOMPATIBILITY • Most biodegradable polymers have hydrolysable linkages,

BIODEGRADABLITY AND BIOCOMPATIBILITY • *Most biodegradable polymers have hydrolysable linkages, namely ester, orthoester, anhydride, carbonate, amide, urea, and urethane in their backbones.* • Biodegradable polymer breaks down into metabolic products* by hydrolysis or enzymatic action.* *Biodegradable polymers are gaining popularity because they i) are reduced to soluble fragments that either excretable or metabolized under physiological conditions ii) can deliver a wide range of drugs to diseased tissues for a prolonged period and iii) can avoid chronic inflammation and long-term complications.*

BIODEGRADABLITY AND BIOCOMPATIBILITY • There are number of products commercially available;

BIODEGRADABLITY AND BIOCOMPATIBILITY • There are number of products commercially available; Decaptyl®, Lupron Depot®, Zoladex®, Adriamycin®, and Capronor®. ZOLADEX® (goserelin acetate implant), contains a potent synthetic decapeptide analogue of luteinizing hormone-releasing hormone (LHRH), also known as gonadotropin releasing releasing hormone (GnRH) agonist analogue. • *Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application. • Although polymeric materials offer desirable properties, such as high tensile strength, in vitro and in vivo stability and biodegradability, they are not necessarily compatible with the human body.*

Bioadhesive / Mucoadhesive Polymers • A bioadhesive polymer can adhere

Bioadhesive / Mucoadhesive Polymers • A bioadhesive polymer can adhere to a biological substance and remain there for an extended period of time. • If the biological substance is mucus, then the bioadhesive polymer is referred as a mucoadhesive polymer. • Bioadhesive polymers are either polyacrylic acid or cellulose derivatives. • Polyacrylic polymers include carbopol, polycarbophil, polyacrylate, poly(2-hydroxyethyl methacrylate) and poly(methacrylate). • Cellulose derivatives include carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, and methylhydroxyethyl cellulose. Some other bioadhesive polymers include chitosan, gums, poly(vinylpyrrolidone), and poly(vinyl alcohol).

CHARACTERISTICS OF AN IDEAL POLYMER • Should be versatile and possess a wide range of mechanical,

CHARACTERISTICS OF AN IDEAL POLYMER • Should be versatile and possess a wide range of mechanical, physical & chemical properties. • Should be non-toxic & inexpensive • Should have good mechanical strength and should be easily administered • Should be easy to fabricate • Should be inert to host tissue and compatible with environment • The polymer should be soluble and easy to synthesize • It should have finite molecular weight and be compatible with biological environment and should be biodegradable • It should provide good drug polymer linkage

ENVIRONMENTALLY RESPONSIVE SYSTEM • It is also possible for a drug delivery system

ENVIRONMENTALLY RESPONSIVE SYSTEM • It is also possible for a drug delivery system to be designed so that it is incapable of releasing its agent or agents until it is placed in an appropriate biological environment. •* Controlled release systems are initially dry and, when placed in the body, will absorb water or other body fluids and swell* • The swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment.

Examples of Water Soluble Polymers Carbomer, Carbopol: is a high molecular weight polymer o

Examples of Water Soluble Polymers *Carb*omer, Carbopol: is a high molecular weight polymer of* acrylic acid *and contains a high proportion of carboxyl groups. It is* used as a suspending agent and as a tablet binding agent.* Cellulose Derivatives:* Ethyl cellulose -insoluble in hot and cold water* methyl cellulose- soluble in water and gel on heating *ethyl methylcellulose -poorly soluble in hot and cold water-does not gel* sodium carboxymethylcellulose- soluble in water *Acacia solutions are highly viscous in water. It is one of the most widely used emulsifiers and thickeners.* *Dextran: Partially hydrolyzed dextran are used as plasma substitutes or expanders to restore or maintain blood volume.* Polyvinylpyrrolidone *(PVP): is used as a suspending, dispersing, tablet binding, and granulating agent.* Polyethylene glycol *(PEG): is used to increase drug solubility.*

Factors Affecting Tg • Length of po

Factors Affecting Tg • Length of polymer chain • Polymer chain side group • Polymer chain flexibility • Polymer chain branching • Polymer chain cross-linking • Processing rate • Plasticizers

For the reservoir systems the drug delivery rate

For the reservoir systems the drug delivery rate can remain fairly constant. • In this design, a reservoir containing whether solid drug, dilute solution, or highly concentrated drug solution within a polymer matrix is surrounded by a film or membrane of a rate-controlling material. • The only structure effectively limiting the release of the drug is the polymer layer surrounding the reservoir. •* This polymer coating is uniform and of a non-changing thickness, the diffusion rate of the active agent can be kept fairly stable throughout the lifetime of the delivery system.*

GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER • There are three primary mechanisms

GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER • There are three primary mechanisms by which active agents can be released from a delivery system: Diffusion, Degradation, and Swelling followed by diffusion • Any or all of these mechanisms may occur in a given release system • Diffusion occurs when a drug or other active agent passes through the polymer that forms the controlled-release device. • The diffusion can occur on a macroscopic scale through pores in the polymer matrix or • on a molecular level, by passing between polymer chains

Glass Transition Temperature (Tg) • Crystal melts- polymer

Glass Transition Temperature (Tg) • Crystal melts- polymer volume increases as solid turns into liquid. • *Melting temp. (Tm) represents first-order transition in polymers* • Volume of an amorphous polymer changes over a wide range of temp. -*Tg - second order transition* *• Tg is a expression of molecular motion-dependent on many factors. • Tg is not an absolute property of the material • It is influenced by factors affecting the movement of polymer chains* • At temp. below Tg - amorphous polymers are hard, stiff and glassy (they may not be brittle) • At temp. above Tg- polymers are rubbery and may as well flow.

MOLECULAR STRUCTURE & SHAPE • The mechanical properties are also governed b

MOLECULAR STRUCTURE & SHAPE • The mechanical properties are also governed by the structure of the polymer chains. • The mechanical properties of a polymer are dictated in part by the shape of the chain.

MOLECULAR WEIGHT • When polymers are fabricated, there will always be a dis

MOLECULAR WEIGHT • When polymers are fabricated, there will always be a distribution of chain lengths. • The properties of polymers depend heavily on the molecule length. • There are two ways to calculate the *average molecular weight:* 1. Number Average Molecular Weight The number average molecular weight is the total weight of the sample divided by the number of molecules in the sample. 2. Weight Average Molecular Weight *The calculation of the weight average molecular weight requires that you know the Weight Fraction, Wi, of each type of molecule (or the fraction of the total weight represented by each type of molecule).*

POLYMER CRYSTALLINITY • Polymers -different thermal, physical and mechanical

POLYMER CRYSTALLINITY • Polymers -different thermal, physical and mechanical properties depend on their: • Structure, molecular weight, linearity, intra and intermolecular interactions. • Thermoplastic polymers go through a series of changes with changes in temperature. (Similar to ceramic glasses) • Structure of polymer is so irregular that crystal formation in such cases is not feasible, hence they form glass instead of solid domains. • In their solid form they can be* semi-crystalline or amorphous (glassy).*

POLYMERS Structural units are repeated multifold

POLYMERS Structural units are repeated multifold to make up a polymer. To accent the repetition, a subscript n is frequently placed after the closing bracket, for example, -[-CH2CH2-]n-. End groups are the structural units that terminate polymer chains. When end groups are specified, they are shown outside the brackets, for example, CH3CH-[-CH2CH2-]-CH=CH2

Pharmaceutical Significance of Tg • Tg is an important factor for solid dosage forms.

Pharmaceutical Significance of Tg • *Tg is an important factor for solid dosage forms. • E.g. a chewable dosage form needs to be soft and flexible at mouth temperature of 37 °C.* • Polymer used as a chewable matrix should be soft at this temperatures. Polymers with their Tgs close to this temperature will be apt for these kind of dosage forms. • E.g *Nicorette gum (Nicotine) ---used for smoking cessation Intermittent chewing of the gum by patient leads to low levels of nicotine release (felt by tingling sensation).* Should stop chewing when he/she feels the tingling sensation and repeat it after 30 min or so.

Stimuli-Sensitive Polymers and Copolymers • Stimuli-sensitive polymers ex

Stimuli-Sensitive Polymers and Copolymers • Stimuli-sensitive polymers exhibit large and sharp changes in their swelling and solubility properties in response to small changes in pH or temperature. • *When a soluble polymer is stimulated to precipitate, it will be selectively removed from solution. When such polymers are grafted or coated onto a solid support, one may reversibly change the water absorption into the coated polymer, thus changing the wettability of the surface.* • When a hydrogel is stimulated to collapse, it will squeeze out of its water and shrink in size.

• Homopolymers are composed of sin

• Homopolymers are composed of single atom type polymer chain or backbone • Heterochain polymers contain more than one atom type in the backbone. Examples: polyethers or polyesters • Copolymers are formed from more than one monomer types. Chemical reactivity of polymers depends on the chemistry of their monomer units, but their properties depend to a large extent on the way the monomers are put together

• In copolymers, monomeric units may be distributed randomly

• In copolymers, monomeric units may be distributed randomly (random copolymer), in alternating fashion (alternating copolymer), or in blocks (block copolymer). • A graft copolymer consists of one polymer branching from the backbone of the other. • Polymers can be linear, star or branched, giving rise to so-called star block copolymers. • When blocks of A and B monomers alternate in the backbone, the polymer is known as AB multiblock copolymer. • If the backbone consists of a single block of each, it is an AB diblock copolymer. Other possibilities include ABA or ABC triblock copolymers. • Star polymers contain three or more polymer chains.

• Most of the materials used in swelling-controlled release systems are based on hydrogels,

• Most of the materials used in swelling-controlled release systems are based on hydrogels, which are polymers that *swell without dissolving* when placed in water or other biological fluids. • Hydrogels can absorb a great deal of fluid and, at equilibrium, typically comprise* 60-90% fluid and only 10-30% polymer.*

• Polymers or Biomaterials are large molecular weigh

• Polymers or Biomaterials are large molecular weight natural or synthetic molecules made up of small repeating units. • Polymers are synthesized from simple molecules called monomers by a process called polymerization. • If only a few monomer units are joined together, the resulting low-molecular weight polymer is called an oligomer. •* The structural unit enclosed by brackets or parentheses is referred to as the repeating unit or monomeric unit. Polymers can be water soluble or water insoluble.*

Pharmaceutical Applications of Polymers

• • • • • • • • • • Pharmaceutical Applications of Polymers Formulation excipients *↑ Solution viscosity ↑ Suspension stability Enteric coating of tablets Disintegrants Suspending, emulsifying & flocculating agents Controlled release dosage forms Site-specific drug delivery* In preparation of transdermal Patches Polymers are also used as film coatings to disguise the unpleasant taste of a drug, to enhance drug stability and to modify drug release characteristics.