industerial 11[r5575677676756767671].pptx

ppt

1. MODIFIED- RELEASE DOSAGE FORMS Industrial Pharmacy Assist. Prof. Dr. Nozad Hussein PhD Pharmaceutics

2. Outline Introduction The rationale behind extended-release pharmaceuticals Controlled release systems Delayed- release oral dosage forms Kinetic of drug release Apllication of controlled release systems USP requirements and FDA Guidance for modified- release dosage forms Clinical considerations in the use of oral modified- release dosage form Packaging and storing modified- release tablets and capsules

3. Conventional designed to forms; Products are provide an immediate release of drug which promptly produces the desired therapy . Modified- release use to describe drug release dosage features forms having based on time, course, and /or location . It is developed by altering the kinetics and site of drug release and absorption in order to achieve specific clinical objectives, such as improved patient compliance , optimized efficac y, and reduced adverse events.

4. Types of modified drug release: Delayed- release products usually are enteric- coated tablets or capsules designed to pass through the stomach unaltered, later to release their medication within the intestinal tract. Controlled- release products are designed to medication in a controlled predetermined rate, duration release their manner, at a and location to achieve and maintain optimum therapeutic blood levels of drug.

5. Repeat-action forms usually contain two immediate release and the second single doses of medication, one for for delayed release. Targeted release describes drug release directed toward isolating or concentrating a drug in a body region, or site for absorption or for drug action. e.g colon targeting

6. Abbreviation Meaning SR sustained release TR timed release XL extended release XR extended release LA Long acting PA Prolonged action CR Controlled release

7. Disadvantages of CRDDS

8. Drugs are used in the treatment acute conditions.

9. Sustained Release Formulations

10. Controlled Release Formulations

11. Targeted Release

12. E.g. Glucotrol ® XL (glipizide) tablets (Pfizer) Covera – HS ® (verapamil HCl) tabs. (Searle)

13. Osmetic pump : ALZET Pump

14. The system is designed such that only a few drops of water are drawn into the tablet each hour. The rate of inflow of water and the function of the tablet depends upon the existence of an osmotic gradient between the contents of the bi- layer core and the fluid in the GI tract. Drug delivery is essentially constant as long as the osmotic gradient remains constant.

15. Effect of coating membrane thickness on the rate and duration of zero- order release of indomethacin from osmotic pressure-controlled gastrointestinal delivery system

16. The drug release rate altered by: from Oros may be Changing the surface area , The thickness or composition membrane, of the Changing the diameter of the drug release orifice. gastrointestinal acidity, alkalinity, The drug-release rate is not affected by fed conditions, or GI motility.

17. é iable 8./# &pot forms employing polymeric films and matricest Type Materials* 1 Barrier coating 2 Fa mbMm t 3 Plastic matrix 4 Repeat action 5 Ion exchange 6 XydropltiJic matrix 7 Epoxy resin beads Beeswax, glyceryl monostearate, ethylcellulose, nylon (Ultiamid IC), a crylicresins (Eudragit retard) Glycefol palmitosteaiate (Precirol), beeswax, glycowzx, castorwax, aluminium monostearate, carnauba wax, glyceryl monostearatc, steatyl alcohol Polyethylene Poly(vinyl acetate) Polymethacrylate Poly(vinyl chloride) Ethylcellulose Cellulose acetylphthalate Amberlite Dowex Car boxym«thyIce8u1os Sodium carboxymethylcellulose Hydroxypropylmethy1c«Ilutose Epoxy resins Microcapiules Soft gelatin depot capsules Polyamides, gelatin hellaG- PEG Poly(vinyl acetate)-REG Di iammatic representation dru 9 coating enteric coat hydrophilic drvg %epoxy resin bead or mic rocapsule otymer Mechanisms Diffusion Erosion, hydrolysis of fat, dissolution Leaching, diffusion Dissolution of enteric C0dt Dissociation of drug- G elation, diffusion Dissolution of resin or erellmg, diffusion Diffusion 'Materials are not atl polymeric. The waxes are included for completeness; these depend on conferring a hydrophobic layer on the drug, tablet, OE gtEft8l0 to prevent access of solvent {After RitKhel, reference 21

18. 5) Multitablet system Small spheroid compressed tablets 3 to 4 mm in diameter may be prepared to have varying drug release characteristics. They may be placed in gelatin capsule shells to provide the desired pattern of drug release. Each capsule may contain 8 to 10 minitablets, some uncoated for immediate release and others coated for extended drug release. Toprol- XL ® (metoprolol succinate) tabs. (Astra); Indocin SR ® (indomethacin capsules (Merck);

19. 6) Complex formation Certain drug substances when chemically combined with certain other chemical agents complexes that may form chemical be only slowly soluble in body fluids, depending upon the pH of the environment. This slow dissolution rate provides the extended release of complex formation the drug. E.g with resin or cyclodextrin

20. The enteric coating may be ; pH dependent , breaking down in the less acidic environment of the intestine, time dependent , eroding by moisture over time during gastrointestinal transit. enzyme dependent, deteriorating as a result of the hydrolysis- catalyzing action of intestinal enzymes.

21. Monday, April 17, 2023 28 Kinetics of Drug release Drug release from conventional dosage forms, like the other processes of ADME, are governed by the first- order kinetics model . In First- order model, drug release is dependent on the amount of drug available for release and therefore the rate of release declines exponentially with time .

22. Monday, April 17, 2023 29 Kinetics of Drug release… Extended release dosage forms are governed by zero- order kinetics in which the rate of release is independent of amount of drug remaining in the dosage form . Therefore a constant amount of drug will be released over time from extended release dosage forms

23. Application of controlled released Ocular application: Glaucoma

24. 2. Contraceptive systems Non- erodible subdermal implants Erodible subdermal implants Steroid releasing iuds Vaginal rings

25. 3. Periodontal disease

26. Hollow fibers for periodontal disease

27. Leuprolide is a hormone therapy. It is used to treat advanced prostate cancer in men, breast cancer, endometriosis, uterine fibroids, and early puberty

28. Risperidone is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder, irritability associated with autistic disorder

29. V. USP requirements and FDA guidance for modified- release dosage forms 1) Drug release The USP test for drug release for extended- release and delayed- release articles is based on drug dissolution from the dosage unit against elapsed test time. Time (hr) 1.0 2.0 4.0 8.0 Amount dissolved between 15% and 40% between 25% and 60% between 35% and 75% not less than 70%

30. 2) Uniformity of dosage units demonstrated by Uniformity of dosage units may be either of two methods, weight variation or content uniformity . 3) In vitro/in vivo correlations (IVIVCs) IVIVCs is critical to the development of oral extended- release products. Assessing IVIVCs is important throughout the periods of product development, clinical evaluation, submission of an application approval for marketing, and approval for any formulation for FDA- during post or manufacturing changes which are proposed.

31. indicates labeling 4) Labeling The USP requirements dosage form for modified- release articles in addition to general labeling requirements.

32. Clinical considerations in the use of oral modified- release dosage forms Patients should be advised of the dose and dosing frequency of modified drug release products and instructed to not use them interchangeably or concomitantly with immediate- release forms of the same drug. Patients should be advised that modified- release tablets and capsules should not be crushed or chewed since such action would compromise their drug release features.

33. Patients should be advised that matrix shells and nonerodible osmotic plastic tablets remain intact throughout gastrointestinal transit and the empty shells or ‘ghosts’ from may be seen in the osmotic tablets stool.

34. Packaging and storing modified- release tablets and capsules Modified- release tablets are packaged and stored and capsules in the same manner as conventional products.