enteric coating polymers

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1. Enteric coating polymers Aram I. Ibrahim University of sulaimani College of pharmacy Dep. of pharmaceutics 2017-04-24

2. Outlines D rug release profiles Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ®) Cellulose esters Polyvinyl derivatives R efferences 2

3. D rug release profiles I mmediate release dosage forms a dosage form is considered as immediate release when 75% of the API is dissolved whithin 45 minutes. Modified release dosage forms Modified-release drug delivery refers to the modification of drug release from a dosage form Extended-release D elay release 3

4. Modified release dosage forms Extended-release Matrix system Water-soluble matrix Water-insoluble matrix Reservoir system Osmotic pump systems Delayed release Enteric- coated systems Colonic-release systems Pulsatile -release systems Bimodal-release systems 4

5. Outlines Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ) Cellulose esters Polyvinyl derivatives R efferences 5

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. 6

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. 7

8. Outlines Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ) Cellulose esters Polyvinyl derivatives R efferences 8

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) . 9

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. 10

11. Solubility of enteric coating polymers cont. E nteric 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. Th is concerns encourage the use of aqueous dispersion systems with 30-40% wt. dry polymer dispersed in water systems 11

12. Outlines Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ®) Cellulose esters Polyvinyl derivatives R efferences 12

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. 13

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. 14

15. Polymethacrylates (EUDRAGIT®) cont. A pplications 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. 15

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 . 16

17. E udragit ® 17

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20. Outlines Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ) Cellulose esters Polyvinyl derivatives R efferences 20

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) C ellulose acetate succinate Cellulose acetate trimellitate Hydroxypropyl methyl cellulose phthalate Hydroxypropyl methyl cellulose acetate succinate 21

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 . 22

23. Cellulose acetate derivatives 23

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 . S olubility of CAP 24

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. A vailable as Powder (Eastman™ C-A-P Cellulose Ester NF) 25

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. 26

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 27

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. 28

29. Outlines Modified release dosage forms Enteric coating Enteric coating polymers Polymethacrylates ( Eudragit ) Cellulose esters Polyvinyl derivatives R efferences 29

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 . 30

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. 31

32. O thers Shellac Zein 32

33. S hellac S hellac 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. 33

34. S hellac cont. Disadvantage When applying as a coating shellac is sticky, and it is not dissolved below the pH of 7. 34

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. 35

36. Dissolution pH of polymers 36

37. R efferences https://www.slideshare.net/garg14ashish/enteric-coating-of-pharmaceutical-products EUDRAGIT A VERSATILE POLYMER : A REVIEW Vikrant K Nikam , Kiran B Kotade , Vinayak M Gaware , Ramdas T Dolas . Pharmacologyonline 1: 152-164 (2011) . Eudragit : a technology evaluation Seema Thakral , Naveen K Thakral & Dipak K Majumdar † † University of Delhi, Delhi Institute of Pharmaceutical Sciences and Research (Formerly College of Pharmacy), Department of Pharmaceutics, New Delhi, India. https://www.slideshare.net/yusufnawazkhan/enteric-coating?qid=f9557f4b-b877-4e01-8059-1becfd1f19da&v=&b=&from_search=6 A REVIEW ON DEVELOPMENT OF HPMCP BASED AQUEOUS ENTERIC COATING POLYMER Ahuja Naresh1 * and Bhandari Anil2 , Devendra Yadav , Atul Garg and Sanjay Khanna 1Department of Pharmaceutics Bharti Institute of Pharmaceutical Sciences, Sri Ganganagar , Rajasthan, India 2012. Application of Cellulose and Cellulose Derivatives in Pharmaceutical Industries Javad Shokri and Khosro Adibkia A review on recent advances of enteric coating Singh Deep Hussan *, Roychowdhury Santanu , Verma P., Bhandari V. Sri Sai College of Pharmacy, badhani , pathankot , India Human Journals Review Article June 2016 Vol.:6, Issue:3 © All rights are reserved by MD. SAIFUL ISLAM et al. A Review on Biodegradable Polymers for Enteric Coating Material . 37

38. Thank you 38