DIFFERENT POLYMERS USED IN DESIGNING NDDS
INTRODUCTION
The philosophy behind the development of controlled drug delivery systems is to make a therapeutic agent do its best when administered into the body. This means a high therapeutic efficacy with minimal toxicity Successful application of many therapeutic agents are hampered by a multitude of problems Drugs administered normally distribute throughout the body interacting not only with the target cells but also with the normal healthy cells which often results in toxic effects. Conventional therapy requires frequent administration of the therapeutic agent to the patient which reduces patient compliance. Systemic Administration of the drug often requires high concentrations to maintain a therapeutic effect because the dilution effect and the difficulty of drug placement in the target site (Chien, 1982). To obtain maximum therapeutic efficacy, It becomes necessary to deliver the agent to the target tissue in the optimal a for the right period of time thereby causing little toxicity and minimal side effects. A well designed Controlled drug delivery system can overcome some of
the problems of conventional therapy and enhance the therapeutic efficacy of a given
drug.
A thorough understanding of the drug carrier, the drug and the target site is necessary for designing a controlled drug delivery system. Choice of the method for achieving controlled release in a part application depends on the physico-chemical properties of the carrier system, potency and properties of the drug and the location and access to the target site. Drug release from a carrier matrix is governed by the interaction of the drug with the carrier matrix. For example, the free aldehyde in glutaraldehyde cross-linked microspheres react with certain drugs. Methotrexate reacts with glutaraldehyde while adriamycin does not even though both contain an amino group (Oppenheim, 1986). Accessibility d functional group may also exert an influence. Since the physico-chemical properties of each drug is ch different, the release profiles of different drugs can be different from a given carrier matrix It therefore becomes necessary to evaluate in detail the behaviour of each drug individually in terms of its interaction with the matrix and the release profile.
There are various approaches in delivering a therapeutic substance to the target site in a sustained or controlled release fashion. One such approach is using polymeric microspheres as carriers for drugs Microspheres of biodegradable and non biodegradable polymers have been investigated for sustained release depending on the final application. In the case of non-biodegradable drug carrier when administered parenterally, the carrier remaining in the body after the drug is completely released poses the possibility of carrier toxicity over a long period of time.
CHARACTERISTICS OF IDEAL POLYMER
Low Density.
Low coefficient of friction.
Good corrosion resistance.
Good mould ability.
Excellent surface finish can be obtained.
Can be produced with close dimensional tolerances.
Economical.
Poor tensile strength.
Low mechanical properties.
Poor temperature resistance.
Can be produced transparent or in different colour.
CLASSIFICATION
The Polymers used in NDDS can be classified broadly as:
1. Classification based on source
2. Classification based on structure
3. Classification based on polymerisation
4. Classification based on molecular force
Classification based on source:
Natural polymers -
The definition of a natural polymer is a polymer that results from only raw materials that are found in nature. Exam-
Proteins, Cellulose, Starch, Rubber.
Semi-synthetic polymers –
The polymer can obtained both Natural as well as Synthetic origin is known as Semi-synthetic polymer. Example - Cellulose derivatives - Cellulose acetate (Rayon).
Synthetic polymers -
T are the polymer was prepared by Laboratory is known as Synthetic Polymer. Example - Buna-S, Buna-R, Nylon, Polythene, Polyester.
NATURAL POLYMERS AND MODIFIED NATURAL POLYMERS
Biopolymers or natural polymers are an attractive class of biodegradable polymer since they are: Derived from natural sources Easily available Relatively cheap Qualified for a number of chemical modification .The natural
polymers can be proteins and polysaccharides in chemical origin. The modified natural polymers are natural polymers altered to improve their biodegradation profile. Generally labile polar functionalities are added to the polymer to enhance the degradability of the polymer. The extent and nature of polymer modification is vital as excess modification can hamper the biodegradation and the added functional group may be converted to toxic degradation products. This modification of natural polymers is achieved by chemical modification or enzymatic alteration. The example of chemical modification is the cross-linking of gelatin using formaldehyde. The chemical modification involves harsh conditions in comparison to the enzymatic method. The various potential natural and modified biopolymers for biomedical applications are discussed below:
Collagen
Collagen, the primary structural protein occurs in the animal tissues, as aligned fibres in skin, connective tissue and the organic substance of bone. The prime function of collagen is to check tissue deformation and avoid mechanical failure.
They offer the following advantages:
Easy to isolate and purify in large quantities.
Biocompatible and non-toxic profile.
Well-established physicochemical, structural and immunological properties.
Amenable to easy processing to various forms.
Some of the unwarranted properties that can impose limitations on designing of viable drug delivery systems are:
Tissue In vivo swelling and resultant poor dimensional stability
Variability in drug release kinetics
Low mechanical strength and elasticity in vivo
Residual aldehyde cross-linking agents cause irritation.
Albumin
Albumin is a major plasma protein component. In the human plasma it accounts for more than 55 % of the total protein. They have been employed to design particulate drug delivery systems. The prime advantages include their biodegradation into natural products, easy availability and absence of toxicity and antigenicity. Albunin microspheres have been employed to deliver many drugs including insulin norgestrel, haematoporphyrin, sulphadiazine, prednisolone, triamcinolone,5 fluorouracil, doxorubicin and mitomycin C. Basically, the albumin microspheres have been exploited for chemotherapy as with them high local drug concentration can be achieved for a relatively longer time period.
Various factors affecting the drug release from albumin microspheres are:
Physicochemical properties and concentration of the drug.
Interaction between the drug and albumin matrix.
Size and density of the microsphere.
Nature and degree of cross-linking.
Presence of enzymes and pH of the environment.
Gelatin
Gelatin is a heterogenous product obtained by irreversible hydrolytic extraction of treated animal collagen. This partial hydrolysis converts the tough fibrous collagen into an unoriented water-soluble protein.
The gelatin offers certain advantages like easy availability, low antigen profile, poor
binding lo drug molocules and low termpature preparation technique that reduces the
chances of drug degradation.
Chitin and Chitosan
Chitin is a linear polycationic polymer of N-acetyl- D-glucosamine(N-aceryl-2-amino-2-deoxy-D-gluco-pyranose).
The characteristic properties of chitosan that render them suitable for pharmaceutical and biomedical applications are:
1. Pharmacological properties like antacid and antiulcer activity, hypocholesterolemic action and wound healing properties.
2. Haemostatic and spermicídal properties owing to their ability to bind strongly to mammalian cells by virtue of their polycationic character.
3. Presence of reactive functional group and cationic character opens up possibilities for their application in controlled drug delivery.
4.Favourable biological properties like biodegradability, biocompatibility and non- toxicity.
5. Has gel-forming ability at low pH.
.SYNTHETIC POLYMERS
Aliphatic Poly (ester)
Among the degradable polymers identified till date, the ester bond containing aliphatic polyesters are the most attractive and promising owing to their remarkable biocompatibility and versatility in terms of physical, chemical and biological properties. The prominent members of this class of polymers are presented . Out of these only a few polymers (e.g., PLA, PGA, PCL and their copolymers) have reached the clinical stages as biosorbable drug delivery devices since in addition to biodegradable profile they have to meet other prerequisites for clinical use and commercialization.
Polycondensation of Bifunctional Hydroxy Acids
Lactic acid, glycolic acid and hydroxycaproic acid can be condensed at low pressure
and high temperature.
. Lactide / Glycolide Polymers
Poly (glycolic acid) was the first degradable polymer to appear way back in 1954. At first it was abandoned for further development due to its poor thermal and hydrolytic stability.
# Poly-E-caprolactone (PCL) and its Copolymers
PCL was identified as a biodegradable polymer in the 1970s. The earlier suggested
use of PCL was as a component in biodegradable packaging to curtail environmental
pollution.
The advantages of PCL as biodegradable controlled drug delivery systems
include:
Its slow degradation rate renders it suitable for use in long-term (1 year) delivery systems.
Biodegradability can be increased by copolymerization.
High permeability to a large number of drug moieties.
Non-toxic profile.
Its unique ability to form compatible blends with many other polymers.
Classification based on structure
1.Linear polymers - The smallest repeating unit arrange in straight line path is known as Linear polymer. Example – poly vinyl chloride.
2. Branched chain polymers - Contain linear chains having some
branches, Example - low density polymer.
3. Cross linked chain polymers - formed from bi-functional and
tri-functional monomers and contain strong covalent bonds.
Example - bakelite, melamine.
Classification based on polymerization
• Addition polymers
Formed by the repeated addition of monomer molecules possessing double or triple
bonds.
n(CH2=CH2) -(CH2 -CH2 )- Ethylene polyethylene
One from of polymer is converted into anther from of polymer loss of atoms, ion, from Molecule.
• Condensation polymers
Formed by repeated condensation reaction between two different bi-functional or
trifunctional monomeric units.
e.g. terylene (dacron), nylon 6, 6, nylon 6.
One polymer can converted into anther from of polymer without loss of atoms, ion, from molecule.
Classification based on molecular force
Nylon :- Nylon is used as general name for all synthetic fiber forming polyamides,i.e., having a protein like structure. These are the condensation polymers of diamine and dibasic acids A number is usually suffixed with the Nylon which refers to the number of carbon atoms present in the diamine and the dibasic acids respectively.
example: nylon 6,6, nylon-6,6: Nylon-6,6 is obtained by the polymerization of adipic
acid with hexamethylene diamine.
Thermoplastic Polymers:
• These are linear or slightly branched long chain polymers, which can be softened on heating & reversibly hardened on cooling repeatedly. Their hardness is a temporary property & varies with temperature.
• The polymer under heating it can convert one stare to another state and after cooling it can again convert its original state.
example:- polyvinyl chloride
Classification based on molecular force
Thermosetting polymers:
Initial Mixture of Reactive, Low Molar Mass Compounds Reacts Upon Heating In
the Mold To Form An Insoluble, Infusible Network.
Example: Bakelite
Bakelite:
is formed of Phenol And Formaldehyde Polymerization.
GENERAL MECHANISM OF DRUG RELEASE
FROM POLYMER
• Three primary mechanism for drug release ,namely:
Diffusion
Degradation
Water penetration(Swelling)
Any of these mechanism can occur in a given release system Drug release from
polymer by diffusion.
• Rate limiting step is diffusion of drug through inert water insoluble membrane
barrier.
• There are two types,
a) Reservoir
b) Matrix
Reservoir diffusion system
In membrane-controlled reservoir devices, the drug is contained in a core, which is
surrounded by a polymer membrane, and it is released by diffusion through this rate
controlling membrane.
e.g. Poly(N-vinyl pyrrolidone),Poly(ethylene-co-vinyl acetate )
Matrix diffusion system
In these devices, the drug is released either by passing through the pores or between
polymer chains, and these are the processes that control the release rate.
Such as: polyethylene , polyvinylacetate
Degradation
The drug molecules, which are initially dispersed in the polymer, are released as the
polymer starts eroding or degrading.
The four most commonly used biodegradable polymers in drug delivery systems are
poly(lactic acid),poly(lactic-co-glycolic acid),polyanhydrides, poly(ortho esters), and
poly(phosphoesters).
Water penetration (swelling):
•This type of systems are initially dry and when placed in body, absorb water or other fluid and it swells. Swelling increases aq. solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into external environment.
E.g :(N-isopro-pylacrylamide), Ethylene-vinyl alcohol
Bio degradation of polymers :
• Bio degradation is the chemical changes that alter the molecular weight or solubility of the polymers.
• Bio erosion may refer to as physical process that result in weight loss of a polymer
device.
• The erosion of polymers basically takes place by two methods:-
1.Hydrolytic mechanism
2. Enzymatic mechanism
Hydrolytic Mechanism
• Hydrolytic degradation of polymers may be defined as the breaking of chemical bonds in the polymer backbone by the attack of water to form oligomers and finally monomers.
• This kind of hydrolysis could not require of specific biological compounds as proteases.
• All biodegradable polymers contain hydrolysable bonds like glycosides, esters, orthoesters, anhydrides, carbonates, amides
• Rate of hydrolytic degradation is modulated by hydrophilic characteristics of the polymers.
Enzymatic mechanism
• Enzymes are biological catalysts.
• They accelerate reaction rates in living organisms without undergoing themselves any permanent change.
• Hydrolysis reactions may be catalyzed by enzymes known as hydrolases, which include proteases, esterases, glycosidases, and phos‐phatases, among others.
• Enzymatic surface degradation occurs when enzymes cannot penetrate the interior of the polymer, due to high cross-link density or limited access to cleavage points, forcing the surface or exterior bonds to cleave first.
Application of polymers
1 .DRUG DELIVERY OF VARIOUS CONTRACEPTIVES &
HORMONES:
E.g. Medroxyprogesterone acetate–vaginal contraceptive ring
It consists of a drug reservoir & polymer coating material. Through this layer the drug releases slowly.
2)DRUG DELIVERYAND THE TREATMENT OF DIABETES
Here the polymer
will act as barrier between blood stream & insulin.
E.g. polyacrylamide or N,Ndimethylaminoethylmethacrylate
3)APPLICATIONS OF POLYMERS IN SOLID
DOSAGE FORMS:
IN TABLETS
• Polymers like methyl cellulose, hydroxyl ethyl cellulose, hydroxyl ethyl methyl cellulose are used as binders.
• Polymers like carboxyl methyl cellulose sodium is used as disintegrating agent.
• Polymers like all the cellulose derivative are used as coating materials.
• Polymers like cellulose acetate phthalate, hydroxyl propyl methyl cellulose phthalate, polyvinyl acetate phthalate are used as enteric coating material.
INCAPSULES
• Gelatin, a natural polymer which is the major ingredient in the manufacturing of capsules.
4)APPLICATIONS OF POLYMERS IN LIQUID DOSAGE FORMS:
IN SUSPENSIONS
• Polymers like Acacia, Tragacanth, Cellulose derivative, Xanthum gum are used as suspending agents. They should be selected based on their characters like PH, solubility & concentration. They enhances the dispersion of solids in liquids.
IN EMULSIONS
• Polymers like Tragacanth, Spans, Tweens are used as emulsifying agents
Continue
5) Polymers can be used as film coatings to mask the unpleasant taste of a drug & to modify drug release characteristics.
6 )Polyanhydrides are used in CDDS because of their unique property of surface erosion.
7) Hyaluronic acid is used in controlled release ophthalmic preparations.
8) Wide variety of polymers like natural gums are using as thickening agents.
E.g. poly ethylene glycol, carbomer
9) Some of the polymers are using as protective colloids to stabilize suspensions & emulsions.
E.g . Sodium alginate
10)Some polymers can be used as suppository bases.
E.g. poly ethylene glycol
CONCLUSION
The knowledge and skill in the area of biodegradable polymer technology is expanding rapidly. This cutting edge technology has generated a substantial number of biodegradable polymers with a wide range of degradation rates. This has widened the horizon of the options that researchers have at their disposal for controlled and targeted delivery of a whole array of therapeutic moieties. Needless to say that in the recent years the application of biodegradable and environmentally sensitive polymers in drug delivery system has reached dizzy heights. Biospecific polymers and copolymers having suitable chemical groups and or functional monomers have been synthesized. The individual classes of polymers in the family of biodegradable polymers have their distinct characteristics in terms of sbiodegradable- degradation, biocompatibility, stability and versatility, and thus their application potential for various delivery applications through different routes of administration is inter play of these factors.
The philosophy behind the development of controlled drug delivery systems is to make a therapeutic agent do its best when administered into the body. This means a high therapeutic efficacy with minimal toxicity Successful application of many therapeutic agents are hampered by a multitude of problems Drugs administered normally distribute throughout the body interacting not only with the target cells but also with the normal healthy cells which often results in toxic effects. Conventional therapy requires frequent administration of the therapeutic agent to the patient which reduces patient compliance. Systemic Administration of the drug often requires high concentrations to maintain a therapeutic effect because the dilution effect and the difficulty of drug placement in the target site (Chien, 1982). To obtain maximum therapeutic efficacy, It becomes necessary to deliver the agent to the target tissue in the optimal a for the right period of time thereby causing little toxicity and minimal side effects. A well designed Controlled drug delivery system can overcome some of
the problems of conventional therapy and enhance the therapeutic efficacy of a given
drug.
A thorough understanding of the drug carrier, the drug and the target site is necessary for designing a controlled drug delivery system. Choice of the method for achieving controlled release in a part application depends on the physico-chemical properties of the carrier system, potency and properties of the drug and the location and access to the target site. Drug release from a carrier matrix is governed by the interaction of the drug with the carrier matrix. For example, the free aldehyde in glutaraldehyde cross-linked microspheres react with certain drugs. Methotrexate reacts with glutaraldehyde while adriamycin does not even though both contain an amino group (Oppenheim, 1986). Accessibility d functional group may also exert an influence. Since the physico-chemical properties of each drug is ch different, the release profiles of different drugs can be different from a given carrier matrix It therefore becomes necessary to evaluate in detail the behaviour of each drug individually in terms of its interaction with the matrix and the release profile.
There are various approaches in delivering a therapeutic substance to the target site in a sustained or controlled release fashion. One such approach is using polymeric microspheres as carriers for drugs Microspheres of biodegradable and non biodegradable polymers have been investigated for sustained release depending on the final application. In the case of non-biodegradable drug carrier when administered parenterally, the carrier remaining in the body after the drug is completely released poses the possibility of carrier toxicity over a long period of time.
CHARACTERISTICS OF IDEAL POLYMER
Low Density.
Low coefficient of friction.
Good corrosion resistance.
Good mould ability.
Excellent surface finish can be obtained.
Can be produced with close dimensional tolerances.
Economical.
Poor tensile strength.
Low mechanical properties.
Poor temperature resistance.
Can be produced transparent or in different colour.
CLASSIFICATION
The Polymers used in NDDS can be classified broadly as:
1. Classification based on source
2. Classification based on structure
3. Classification based on polymerisation
4. Classification based on molecular force
Classification based on source:
Natural polymers -
The definition of a natural polymer is a polymer that results from only raw materials that are found in nature. Exam-
Proteins, Cellulose, Starch, Rubber.
Semi-synthetic polymers –
The polymer can obtained both Natural as well as Synthetic origin is known as Semi-synthetic polymer. Example - Cellulose derivatives - Cellulose acetate (Rayon).
Synthetic polymers -
T are the polymer was prepared by Laboratory is known as Synthetic Polymer. Example - Buna-S, Buna-R, Nylon, Polythene, Polyester.
NATURAL POLYMERS AND MODIFIED NATURAL POLYMERS
Biopolymers or natural polymers are an attractive class of biodegradable polymer since they are: Derived from natural sources Easily available Relatively cheap Qualified for a number of chemical modification .The natural
polymers can be proteins and polysaccharides in chemical origin. The modified natural polymers are natural polymers altered to improve their biodegradation profile. Generally labile polar functionalities are added to the polymer to enhance the degradability of the polymer. The extent and nature of polymer modification is vital as excess modification can hamper the biodegradation and the added functional group may be converted to toxic degradation products. This modification of natural polymers is achieved by chemical modification or enzymatic alteration. The example of chemical modification is the cross-linking of gelatin using formaldehyde. The chemical modification involves harsh conditions in comparison to the enzymatic method. The various potential natural and modified biopolymers for biomedical applications are discussed below:
Collagen
Collagen, the primary structural protein occurs in the animal tissues, as aligned fibres in skin, connective tissue and the organic substance of bone. The prime function of collagen is to check tissue deformation and avoid mechanical failure.
They offer the following advantages:
Easy to isolate and purify in large quantities.
Biocompatible and non-toxic profile.
Well-established physicochemical, structural and immunological properties.
Amenable to easy processing to various forms.
Some of the unwarranted properties that can impose limitations on designing of viable drug delivery systems are:
Tissue In vivo swelling and resultant poor dimensional stability
Variability in drug release kinetics
Low mechanical strength and elasticity in vivo
Residual aldehyde cross-linking agents cause irritation.
Albumin
Albumin is a major plasma protein component. In the human plasma it accounts for more than 55 % of the total protein. They have been employed to design particulate drug delivery systems. The prime advantages include their biodegradation into natural products, easy availability and absence of toxicity and antigenicity. Albunin microspheres have been employed to deliver many drugs including insulin norgestrel, haematoporphyrin, sulphadiazine, prednisolone, triamcinolone,5 fluorouracil, doxorubicin and mitomycin C. Basically, the albumin microspheres have been exploited for chemotherapy as with them high local drug concentration can be achieved for a relatively longer time period.
Various factors affecting the drug release from albumin microspheres are:
Physicochemical properties and concentration of the drug.
Interaction between the drug and albumin matrix.
Size and density of the microsphere.
Nature and degree of cross-linking.
Presence of enzymes and pH of the environment.
Gelatin
Gelatin is a heterogenous product obtained by irreversible hydrolytic extraction of treated animal collagen. This partial hydrolysis converts the tough fibrous collagen into an unoriented water-soluble protein.
The gelatin offers certain advantages like easy availability, low antigen profile, poor
binding lo drug molocules and low termpature preparation technique that reduces the
chances of drug degradation.
Chitin and Chitosan
Chitin is a linear polycationic polymer of N-acetyl- D-glucosamine(N-aceryl-2-amino-2-deoxy-D-gluco-pyranose).
The characteristic properties of chitosan that render them suitable for pharmaceutical and biomedical applications are:
1. Pharmacological properties like antacid and antiulcer activity, hypocholesterolemic action and wound healing properties.
2. Haemostatic and spermicídal properties owing to their ability to bind strongly to mammalian cells by virtue of their polycationic character.
3. Presence of reactive functional group and cationic character opens up possibilities for their application in controlled drug delivery.
4.Favourable biological properties like biodegradability, biocompatibility and non- toxicity.
5. Has gel-forming ability at low pH.
.SYNTHETIC POLYMERS
Aliphatic Poly (ester)
Among the degradable polymers identified till date, the ester bond containing aliphatic polyesters are the most attractive and promising owing to their remarkable biocompatibility and versatility in terms of physical, chemical and biological properties. The prominent members of this class of polymers are presented . Out of these only a few polymers (e.g., PLA, PGA, PCL and their copolymers) have reached the clinical stages as biosorbable drug delivery devices since in addition to biodegradable profile they have to meet other prerequisites for clinical use and commercialization.
Polycondensation of Bifunctional Hydroxy Acids
Lactic acid, glycolic acid and hydroxycaproic acid can be condensed at low pressure
and high temperature.
. Lactide / Glycolide Polymers
Poly (glycolic acid) was the first degradable polymer to appear way back in 1954. At first it was abandoned for further development due to its poor thermal and hydrolytic stability.
# Poly-E-caprolactone (PCL) and its Copolymers
PCL was identified as a biodegradable polymer in the 1970s. The earlier suggested
use of PCL was as a component in biodegradable packaging to curtail environmental
pollution.
The advantages of PCL as biodegradable controlled drug delivery systems
include:
Its slow degradation rate renders it suitable for use in long-term (1 year) delivery systems.
Biodegradability can be increased by copolymerization.
High permeability to a large number of drug moieties.
Non-toxic profile.
Its unique ability to form compatible blends with many other polymers.
Classification based on structure
1.Linear polymers - The smallest repeating unit arrange in straight line path is known as Linear polymer. Example – poly vinyl chloride.
2. Branched chain polymers - Contain linear chains having some
branches, Example - low density polymer.
3. Cross linked chain polymers - formed from bi-functional and
tri-functional monomers and contain strong covalent bonds.
Example - bakelite, melamine.
Classification based on polymerization
• Addition polymers
Formed by the repeated addition of monomer molecules possessing double or triple
bonds.
n(CH2=CH2) -(CH2 -CH2 )- Ethylene polyethylene
One from of polymer is converted into anther from of polymer loss of atoms, ion, from Molecule.
• Condensation polymers
Formed by repeated condensation reaction between two different bi-functional or
trifunctional monomeric units.
e.g. terylene (dacron), nylon 6, 6, nylon 6.
One polymer can converted into anther from of polymer without loss of atoms, ion, from molecule.
Classification based on molecular force
Nylon :- Nylon is used as general name for all synthetic fiber forming polyamides,i.e., having a protein like structure. These are the condensation polymers of diamine and dibasic acids A number is usually suffixed with the Nylon which refers to the number of carbon atoms present in the diamine and the dibasic acids respectively.
example: nylon 6,6, nylon-6,6: Nylon-6,6 is obtained by the polymerization of adipic
acid with hexamethylene diamine.
Thermoplastic Polymers:
• These are linear or slightly branched long chain polymers, which can be softened on heating & reversibly hardened on cooling repeatedly. Their hardness is a temporary property & varies with temperature.
• The polymer under heating it can convert one stare to another state and after cooling it can again convert its original state.
example:- polyvinyl chloride
Classification based on molecular force
Thermosetting polymers:
Initial Mixture of Reactive, Low Molar Mass Compounds Reacts Upon Heating In
the Mold To Form An Insoluble, Infusible Network.
Example: Bakelite
Bakelite:
is formed of Phenol And Formaldehyde Polymerization.
GENERAL MECHANISM OF DRUG RELEASE
FROM POLYMER
• Three primary mechanism for drug release ,namely:
Diffusion
Degradation
Water penetration(Swelling)
Any of these mechanism can occur in a given release system Drug release from
polymer by diffusion.
• Rate limiting step is diffusion of drug through inert water insoluble membrane
barrier.
• There are two types,
a) Reservoir
b) Matrix
Reservoir diffusion system
In membrane-controlled reservoir devices, the drug is contained in a core, which is
surrounded by a polymer membrane, and it is released by diffusion through this rate
controlling membrane.
e.g. Poly(N-vinyl pyrrolidone),Poly(ethylene-co-vinyl acetate )
Matrix diffusion system
In these devices, the drug is released either by passing through the pores or between
polymer chains, and these are the processes that control the release rate.
Such as: polyethylene , polyvinylacetate
Degradation
The drug molecules, which are initially dispersed in the polymer, are released as the
polymer starts eroding or degrading.
The four most commonly used biodegradable polymers in drug delivery systems are
poly(lactic acid),poly(lactic-co-glycolic acid),polyanhydrides, poly(ortho esters), and
poly(phosphoesters).
Water penetration (swelling):
•This type of systems are initially dry and when placed in body, absorb water or other fluid and it swells. Swelling increases aq. solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into external environment.
E.g :(N-isopro-pylacrylamide), Ethylene-vinyl alcohol
Bio degradation of polymers :
• Bio degradation is the chemical changes that alter the molecular weight or solubility of the polymers.
• Bio erosion may refer to as physical process that result in weight loss of a polymer
device.
• The erosion of polymers basically takes place by two methods:-
1.Hydrolytic mechanism
2. Enzymatic mechanism
Hydrolytic Mechanism
• Hydrolytic degradation of polymers may be defined as the breaking of chemical bonds in the polymer backbone by the attack of water to form oligomers and finally monomers.
• This kind of hydrolysis could not require of specific biological compounds as proteases.
• All biodegradable polymers contain hydrolysable bonds like glycosides, esters, orthoesters, anhydrides, carbonates, amides
• Rate of hydrolytic degradation is modulated by hydrophilic characteristics of the polymers.
Enzymatic mechanism
• Enzymes are biological catalysts.
• They accelerate reaction rates in living organisms without undergoing themselves any permanent change.
• Hydrolysis reactions may be catalyzed by enzymes known as hydrolases, which include proteases, esterases, glycosidases, and phos‐phatases, among others.
• Enzymatic surface degradation occurs when enzymes cannot penetrate the interior of the polymer, due to high cross-link density or limited access to cleavage points, forcing the surface or exterior bonds to cleave first.
Application of polymers
1 .DRUG DELIVERY OF VARIOUS CONTRACEPTIVES &
HORMONES:
E.g. Medroxyprogesterone acetate–vaginal contraceptive ring
It consists of a drug reservoir & polymer coating material. Through this layer the drug releases slowly.
2)DRUG DELIVERYAND THE TREATMENT OF DIABETES
Here the polymer
will act as barrier between blood stream & insulin.
E.g. polyacrylamide or N,Ndimethylaminoethylmethacrylate
3)APPLICATIONS OF POLYMERS IN SOLID
DOSAGE FORMS:
IN TABLETS
• Polymers like methyl cellulose, hydroxyl ethyl cellulose, hydroxyl ethyl methyl cellulose are used as binders.
• Polymers like carboxyl methyl cellulose sodium is used as disintegrating agent.
• Polymers like all the cellulose derivative are used as coating materials.
• Polymers like cellulose acetate phthalate, hydroxyl propyl methyl cellulose phthalate, polyvinyl acetate phthalate are used as enteric coating material.
INCAPSULES
• Gelatin, a natural polymer which is the major ingredient in the manufacturing of capsules.
4)APPLICATIONS OF POLYMERS IN LIQUID DOSAGE FORMS:
IN SUSPENSIONS
• Polymers like Acacia, Tragacanth, Cellulose derivative, Xanthum gum are used as suspending agents. They should be selected based on their characters like PH, solubility & concentration. They enhances the dispersion of solids in liquids.
IN EMULSIONS
• Polymers like Tragacanth, Spans, Tweens are used as emulsifying agents
Continue
5) Polymers can be used as film coatings to mask the unpleasant taste of a drug & to modify drug release characteristics.
6 )Polyanhydrides are used in CDDS because of their unique property of surface erosion.
7) Hyaluronic acid is used in controlled release ophthalmic preparations.
8) Wide variety of polymers like natural gums are using as thickening agents.
E.g. poly ethylene glycol, carbomer
9) Some of the polymers are using as protective colloids to stabilize suspensions & emulsions.
E.g . Sodium alginate
10)Some polymers can be used as suppository bases.
E.g. poly ethylene glycol
CONCLUSION
The knowledge and skill in the area of biodegradable polymer technology is expanding rapidly. This cutting edge technology has generated a substantial number of biodegradable polymers with a wide range of degradation rates. This has widened the horizon of the options that researchers have at their disposal for controlled and targeted delivery of a whole array of therapeutic moieties. Needless to say that in the recent years the application of biodegradable and environmentally sensitive polymers in drug delivery system has reached dizzy heights. Biospecific polymers and copolymers having suitable chemical groups and or functional monomers have been synthesized. The individual classes of polymers in the family of biodegradable polymers have their distinct characteristics in terms of sbiodegradable- degradation, biocompatibility, stability and versatility, and thus their application potential for various delivery applications through different routes of administration is inter play of these factors.
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