This document provides an overview of enteric coating polymers that are used to protect acid-labile drugs and ensure optimal drug absorption. It discusses various categories of enteric coating polymers including polymethacrylates (Eudragit), cellulose esters, and polyvinyl derivatives. Key points include: Eudragit polymers are commonly used methacrylic acid copolymers that are insoluble in gastric fluid but dissolve in the intestine. Cellulose esters like cellulose acetate phthalate are also widely employed. These polymers form films that protect the drug core from gastric conditions and dissolve above pH 6, allowing drug release in the intestines. The solubility and properties of different enteric coating polymers allow controlling
3. Drug release profiles
1. Immediate release dosage forms
a dosage form is considered as immediate release when
75% of the API is dissolved whithin 45 minutes.
1. Modified release dosage forms
Modified-release drug delivery refers to the modification of
drug release from a dosage form
A. Extended-release
B. Delay release
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4. Modified release dosage forms
• Extended-release
1. Matrix system
Water-soluble matrix
Water-insoluble matrix
2. Reservoir system
3. Osmotic pump systems
• Delayed release
Enteric-coated systems
Colonic-release systems
Pulsatile-release systems
Bimodal-release systems
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6. Enteric coating
• Enteric coating is aimed to prevent the formulations from
gastric fluid in the stomach and release the drug component
in the intestinal region.
• There are many polymers which are insoluble at low pH, but
soluble at high pH.
• Enteric coatings are prepared from gastric resistant polymers.
• Drug release rate is controlled by its exposed pH.
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7. Reasons for enteric coating
• To protect acid labile drugs.
• For optimal absorption.
• To prevent gastric stress due to drug irritation.
• To show local action on intestine.
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9. Enteric coating polymers
• Enteric coating polymers can be classified into 3 groups based
on chemical compositions as listed below.
• 1. Polymethacrylates Methacrylic acid/ethyl acrylate.
• 2. Cellulose esters
• Cellulose acetate phthalate (CAP).
• Cellulose acetate trimellitate (CAT).
• Cellulose acetate succinate.
• Hydroxypropylmethylcellulose acetate succinate (HPMCAS)
• Hydroxypropyl methylcellulose phthalate.
• 3. Polyvinyl derivatives
• Polyvinyl Acetate Phthalate (PVAP).
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10. Solubility of enteric coating polymers
• enteric coating polymers generally possess free carboxylic
acid groups on the polymer backbone.
• They are insoluble in acidic media but become de-protonated
and dissolved in basic media at neutral pH values (pH>5).
• Solubility of the polymers depends on the number of
carboxylic acid groups varied in the composition.
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11. Solubility of enteric coating polymers cont.
• Enteric coating polymers dissolve well in organic solvents,
giving a stable coating solution that facilitates faster coating
processes.
• However, the practical use of organic solvents in
pharmaceutical formulations has decreased since organic
solvent residues in final products are restricted by the
authorities.
• This concerns encourage the use of aqueous dispersion
systems with 30-40% wt. dry polymer dispersed in water
systems
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13. Polymethacrylates (Eudragit®)
• Eudragit® is trademark of Rohm GmbH & Co. KG. Darmstadt
(1950).
• It is prepared by the polymerization of acrylic and methacrylic
acids or their esters.
• Eudragit® polymers are copolymers derived from esters of
acrylic and methacrylic acid.
• Eudragit® polymers are available in an aqueous dispersion,
organic solution granules and powders.
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14. Polymethacrylates (Eudragit®)
• Two forms of commercially available enteric acrylic resins are
Eudragit® L and Eudragit® S both resins produces film that are
resistant to gastric fluid.
• Eudragit® L and Eudragit® S are soluble in intestinal fluid at pH
6 to 7 respectively.
• Eudragit® L are available as an organic solution, solid, or
aqueous dispersion. Eudragit® S are available as an organic
solution and solid.
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15. Polymethacrylates (EUDRAGIT®) cont.
• Applications
– Time-controlled drug release by sustained release
formulations.
– Gastro-resistance and gastrointestinal targeting by enteric
formulations.
– Moisture protection and odor/taste masking by protective
formulations.
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16. Polymethacrylates (EUDRAGIT®) cont.
• The types of methacrylic acid copolymers used in enteric
coating are Eudragit® L and S, Eudragit® L 30D.
• Eudragit® L and S are soluble in organic solvents such as
aceton, alcohol, mixtures of alcohol and aceton and
chloroform.
• Eudragit® L , S and 30D, are insoluble in gastric fluids but
dissolve in the intestine.
• Eudragit® 30D dissolves at pH 5.5, Eudragit® L dissolves at pH
above 6, but Eudragit® S dissolves at pH above 7.
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21. Cellulose esters
• Cellulose esters are generally water insoluble polymers with
good film forming characteristics.
• Cellulose esters are widely used in enteric coated drug
delivery systems.
• Examples
– Cellulose acetate phthalate (CAP)
– Cellulose acetate succinate
– Cellulose acetate trimellitate
– Hydroxypropyl methyl cellulose phthalate
– Hydroxypropyl methyl cellulose acetate succinate
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22. Pharmaceutical uses of phthalates
• Resistance to degradation of the tablet/capsule coating in the
acidic environment of the stomach.
• Maintenance of flexibility of solid dosage forms.
• Viscosity modification during production of pharmaceutical
formulations.
• Control of drug-release characteristics of modified-release
preparations.
• Increase of the palatability of bitter tasting formulations.
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24. Cellulose Acetate Phthalate
• Relatively hygroscopic and permeable to gastric fluids and
moisture.
• Films formed from CAP are brittle.
• Dissolves only above pH 6 and delays the absorption of drugs.
• Solubility of CAP
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25. Cellulose Acetate Phthalate cont.
• Cellulose acetate phthalate functions as an enteric coating
because of the presence of ionizable phthalate groups.
• Suitable organic solvents for dissolution of CAP include
acetone, mixtures of acetone and ethanol, isopropanol or
ethanol and methylene chloride.
• Available as Powder (Eastman™ C-A-P Cellulose Ester NF)
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26. HPMC-phthalate
• Introduced into the market in 1971 as alternative cellulose
derivative for enteric coating, and it has been demonstrated
to be an effective and safe material.
• Two types of HPMCP with different in pH-solubilities, HPMCP -
55 and HPMCP -50, are available.
• Moreover, HPMCP -55S, a special type, which is distinguished
by its higher molecular weight, greater film strength and
higher acid resistance properties.
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27. HPMC-phthalate cont.
• Dissolves at a relatively lower pH (5-5.5) than CAP or acrylic
copolymers.
• Stability is higher compared to CAP Absence of labile acetyl
groups
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28. Hypromellose acetate succinate
• In 1985, hypromellose acetate succinate (HPMCAS) was
developed as an aqueous enteric coating material.
• This polymer is a cellulose ester bearing acetyl and succinoyl
groups.
• The unique characteristics of this polymer include the feature
that its dissolution behavior in buffers of various pH values
can be controlled by changing the ratio of succinoyl and acetyl
moieties.
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30. Polyvinyl derivatives
• PVAP is a reaction product of phthalic anhydride and polyvinyl
alcohol, used in pharmaceutical applications to provide
enteric protection to solid dosage forms.
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31. Polyvinyl acetate phthalate
• a commonly and widely used enteric polymer
• PVAP shows a pH-dependent solubility. It is soluble in
methanol, ethanol (95%), and mixed solvent systems such as
methanol or ethanol:acetone (1:1), methanol:methylene
chloride (1:1), etc.
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33. Shellac
• Shellac also called purified lac, is a refined product obtained
from the resinous secretion of a tiny insect Laccifer Lacca Karr.
• There are two grades of shellac, orange shellac and white
shellac.
• Shellac is soluble in ethanol, propylene glycol, ammonia
solutions, and alkaline solutions.
• Shellac used for enteric coating alone or in combination with
other polymers, the ammonia solutions of shellac provide the
best enteric coatings.
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35. Zein
• Zein is a class of prolamine protein found in maize (corn).
• It is usually manufactured as a powder from corn gluten
meal.
• Pure zein is clear, odorless, tasteless, hard, water-insoluble,
and it has a variety of industrial and food uses.
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