Major excipients used in tablets

1. Major excipients used in tablets Part 1

3. Tablet • Tablet is usually a compressed preparation that contains: • 5-10% of the drug (active substance); • 80% of fillers, disintegrants, lubricants, glidants, and binders; and • 10% of compounds which ensure easy disintegration, disaggregation, and dissolution of the tablet in the stomach or the intestine

4. Major excipients used in tablet formulations • Starch pregelatinized 10% • Sodium starch glycolate 10% • Polysorbate 80 10% • PEG 20% • Povidone or PVP 15% • Magnesium stearate 50% • Microcrystalline cellulose 25% • Lactose hydrous or anhydrous or monohydrate or spray dried 40% • Hydroxyl propyl methyl cellulose 20% • Hydroxy propyl cellulose 10% • Colloidal silicone dioxide 10% • Cellulose 10% • Titanium dioxide 25% • Talc 10% The precentage indicates the frequancy of appearance of the excipient in 100 different tablets

5. Polyvidone PVP • Also called : • Povidone • Polyvinylpyrrolidine • E1201 • Water -soluble polymer made from the monomer N-vinylpyrrolidone • PVP is soluble in water and other polar solvents • When it is dry absorbs up to 40% of its weight in atmospheric water • In solution, it has excellent wetting properties and readily forms films. This makes it good as a coating or an additive to coatings

6. Polyvidone PVP uses • It is used as a binder and disintegrant many pharmaceutical tablets • It simply passes through the body when taken orally • However, autopsies have found that crospovidone contributes to pulmonary vascular injury in substance whabusers who have injected pharmaceutical tablets intended for oral • PVP added to iodine forms a complex called povidone-iodine that possesses disinfectant properties • As a food additive, PVP is a stabilizer • Give foods a firmer texture • Help to stabilize emulsions

7. Other uses • Used in personal care products, such as shampoos and toothpastes • Used as thickening agent • It has also been used in contact lens solutions • PVP is the basis of the early formulas for hair sprays and hair gels, and still continues to be a component of some

8. Safety patterns • Generally considered safe • The U.S. Food and Drug Administration (FDA) has approved this chemical for many uses • Documented cases of allergic reactions to PVP/povidone, particularly regarding subcutaneous use and situations where the PVP has come in contact with (internal blood fluids) and mucous membranes

9. Examples of documented cases of allergy • boy having an anaphylactic response after application of PVP-I (PVP-Iodine) for treatment of impetigo • A woman, who had previously experienced urticaria (hives) from various hair products, later found to contain PVP, had an anaphylactic response after povidone-iodine solution was applied internally. • Man experiencing anaphylaxis after taking acetaminophen tablets orally was found to be allergic to PVP

10. Polyethylene glycol(PEG) • Polyether compound with many applications from industrial and medical manufacturing • Prepared by polymerization of ethylene oxide • Commercially available over a wide range of molecular weights from 300 g/mol to 10,000,000 g/mol • Different molecular weights have : • Different physical properties (e.g., viscosity) due to chain length effects • Their chemical properties are nearly identical.

11. Medical uses of PEG • Laxatives • Basis of many skin creams • Sexual lubricants , frequently combined with glycerin • Whole bowel irrigation ( • When attached to various protein medications, polyethylene glycol allows a slowed clearance of the carried protein from the blood • This makes for a longer-acting medicinal effect and reduces toxicity allows longer dosing intervals • Examples include PEG-interferon alpha, which is used to treat hepatitis C, and PEG-filgrastim (Neulasta), which is used to treat neutropenia • It has been shown that polyethylene glycol can improve healing of spinal injuries in

12. Research for new clinical uses • High-molecular-weight PEG, e.g., PEG 8000, has been shown to be a dietary preventive agent against colorectal cancer in animal models

13. Other uses • Polyethyleneglycol is the primary component in a type of antifreeze solution used in automobiles and boats as a low-toxicity alternative to the traditional highly poisonous ethylene glycol solutions used in standard antifreeze products

14. Safety patterns • PEGs contain potential toxic impurities such as ethylene oxide and 1,4-dioxane • PEGs are nephrotoxic if applied to damaged skin • Formulations containing it must be used with caution in renal failure patients

15. As excipient • PEG is also used in lubricant eye drops • Tablet binders, film coatings, and lubricants

16. Magnesium stearate • Also called octadecanoic acid, magnesium salt • It is E470b • Magnesium stearate is manufactured from both animal and vegetable oils • Some nutritional supplements specify that the magnesium stearate used is sourced from vegetables • It is a white substance which is solid at room temperature

17. Uses • Diluent in tablets, capsules and powders • Lubricant • Studies have shown that magnesium stearate may affect the release time of the active ingredients in tablets • no reduction in the over-all bioavailability of the ingredients • Magnesium stearate is used to bind sugar in hard candies. • Common ingredient in baby formulas

18. Safety pattern • Considered safe for human consumption at levels below 2500 mg/kg per day • At large doses show laxative eefect

19. Microcrystalline cellulose • Term for refined wood pulp • Not compatible with oxidizing agents like titanium oxide ,potassium oxide ..

20. Uses • Disintegrant • Diluent • Adsorbent • Binder • Some lubricant effect

21. Safety patterns • FDA approved • In concentrations used in pharmaceutical industry no effect • At large doses can cause laxative effect • Abuse of formulations containing it(inhalor and injection )causes cellulose granuloma

22. Lactose • is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose • Several different forms are available • Lactose monohydrate • Anhydrous A-lactose • Anhydrous B –lactose

23. Catabolism • IThe intestinal villi secrete the enzyme called lactase (β-D-galactosidase) to digest it • This enzyme cleaves the lactose molecule into its two subunits, the simple sugars glucose and galactose, which can be absorbed • Production of lactase gradually decreases with maturity due to a lack of constant consumption

24. Lactose intolerance • Lactose is not broken down and provides food for gas-producing gut flora, which can lead to bloating, flatulence, and other gastrointestinal symptoms

25. Uses • Diluent and filler for: • Tablet • Capsules • Diluent for infant feed formulas • Diluent for dry powder inhalors • With sucrose used in coating (1:3)

26. Safety pattern • FDA approved in tablet capsule and parentral routes • Lactose intolerance is its major adverse reaction