B.ph., iii yr sem v, Tablets .pptx, IP-I

Tablets

1. Tablets Dr. M. N.Chishti , Assist Prof, Dept of Pharmaceutics

2. Tablet is defined as a compressed solid dosage form containing medicaments with or without excipients . According to the Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or biconvex, unit dosage form, prepared by compressing a drugs or a mixture of drugs, with or without diluents. They vary in shape and differ greatly in size and weight, depending on amount of medicinal substances and the intended mode of administration. It is the most popular dosage form and 70% of the total medicines are dispensed in the form of Tablet. All medicaments are available in the Tablet form except where it is difficult to formulate or administer.

3. The advantages of the Tablet dosage form are: They are unit dosage form and offer the greatest capabilities of all oral dosage form for the greatest dose precision and the least content variability. Cost is lowest of all oral dosage form. Lighter and compact. Easiest and cheapest to package and strip. Easy to swallowing with least tendency for hang‐up. Sustained release product is possible by enteric coating.

4. 7. Objectionable odour and bitter taste can be masked by coating technique. 8. Suitable for large scale production. 9. Greatest chemical and microbial stability over all oral dosage form. 10. Product identification is easy and rapid requiring no additional steps when employing an embossed and/or monogrammed punch face.

5. Disadvantages of Tablet dosage form are: Difficult to swallow in case of children and unconscious patients. Some drugs resist compression into dense compacts, owing to amorphous nature, low density character. Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT may be difficult to formulate or manufacture as a tablet that will still provide adequate or full drug bioavailability. Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating. In such cases, capsule may offer the best and lowest cost .

6. General properties of Tablet dosage forms: A tablet should have elegant product identity while free of defects like chips, cracks, discoloration, and discoloration, and contamination. Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing. Should have the chemical and physical stability to maintain its physical attributes over time. The tablet must be able to release the medicinal agents in a predictable and reproducible manner. Must have a chemical stability over time so as not to follow alteration of the medicinal agents.

7. Tablets ingested orally: Compressed tablet, e.g. Paracetamol tablet Multiple compressed tablet Repeat action tablet Delayed release tablet, e.g. Enteric coated Bisacodyl tablet Sugar coated tablet, e.g. Multivitamin tablet Film coated tablet, e.g. Metronidazole tablet Chewable tablet, e.g. Antacid tablet (B) Tablets used in oral cavity: Buccal tablet, e.g. Vitamin‐c tablet Sublingual tablet, Troches or lozenges Dental cone (C) Tablets administered by other route: Implantation tablet Vaginal tablet, e.g. Clotrimazole tablet

8. (D) Tablets used to prepare solution: Effervescent tablet, e.g. Dispirin tablet (Aspirin) Dispensing tablet, e.g. Enzyme tablet ( Digiplex ) Hypodermic tablet Tablet triturates e.g. Enzyme tablet ( Digiplex )

9. Tablet Ingredients: In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Different excipients are: 1. Diluent 2. Binder and adhesive 3. Disintegrents 4. Lubricants and glidants 5. Colouring agents 6. Flavoring agents 7. Sweetening agents

10. Diluent : Diluents are fillers used to make required bulk of the tablet when the drug dosage itself is inadequate to produce the bulk. Secondary reason is to provide better tablet properties such as improve cohesion, to permit use of direct compression manufacturing or to promote flow. A diluent should have following properties: They must be non toxic They must be commercially available in acceptable grade There cost must be low They must be physiologically inert They must be physically & chemically stable by themselves & in combination with the drugs. They must be free from all microbial contamination. They do not alter the bioavailability of drug. They must be color compatible.

11. Commonly used tablet diluents Lactose‐anhydrous and spray dried lactose Directly compressed starch‐ Sta Rx 1500 Hydrolyzed starch‐ Emdex and Celutab Microcrystalline cellulose‐ Avicel (PH 101and PH 102) Dibasic calcium phosphate dehydrate Calcium sulphate dihydrate Mannitol Sorbitol Sucrose‐ Sugartab , DiPac , Nutab 10. Dextrose

12. 2. Binders and Adhesives: These materials are added either dry or in wet‐ form to form granules or to form cohesive compacts for directly compressed tablet. Example: Acacia, tragacanth ‐ Solution for 10‐25% Conc. Cellulose derivatives‐ Methyl cellulose, Hydroxy propyl methyl cellulose, Hydroxy propyl cellulose Gelatin‐ 10‐20% solution Glucose‐ 50% solution Polyvinylpyrrolidone (PVP)‐ 2% conc. Starch paste‐10‐20% solution

13. 3. Disintegrants : Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT. Example: Starch‐ 5‐20% of tablet weight. Starch derivative – Primogel and Explotab (1‐8%) Clays‐ Veegum HV, bentonite 10% level in colored tablet Cellulose derivatives‐ (sodium carboxy methyl cellulose) Sodium Alginate PVP ( Polyvinylpyrrolidone )

14. Superdisintegrants : Swells up to ten fold within 30 seconds when contact water. Example: Crosscarmellose ‐ cross‐linked cellulose, Crosspovidone ‐ cross‐linked povidone (polymer), Sodium starch glycolate ‐ cross‐linked starch. These cross‐ linked products swell upto 10n fold with in 30 seconds when in contact with water. A portion of disintegrant is added before granulation and a portion before compression, which serve as glidants or lubricant. Evaluation of carbon dioxide in effervescent tablets is also one way of disintegration.

15. 4. Lubricant and Glidants : Lubricants are intended to prevent adhesion of the tablet materials to the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of the tablet granulation. Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles. Example: Lubricants ‐ Stearic acid, Stearic acid salt ‐ Stearic acid, Magnesium stearate , Talc, PEG (Polyethylene glycols), Surfactants Glidants ‐ Corn Starch – 5‐10% conc., Talc‐5% conc., Silica derivative ‐ Colloidal silicas such as Cab‐O‐ Sil , Syloid , Aerosil in 0.25‐3% conc.

16. 5. Coloring agent: The use of colors and dyes in a tablet has three purposes: (1) Masking of off color drugs (2) Product Identification (3) Production of more elegant product All coloring agents must be approved and certified by FDA. Two forms of colors are used in tablet preparation – FD &C and D & C dyes. These dyes are applied as solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and employed as dry powder coloring. Example: FD & C yellow 6‐sunset yellow FD & C yellow 5‐ Tartrazine FD & C green 3‐ Fast Green FD & C blue 1‐ Brilliant Blue FD & C blue 2 ‐ Indigo carmine D & C red 3‐ Erythrosine. D & C red 22 – Eosin Y

17. 6. Flavoring agents: For chewable tablet‐ flavor oil are used 7. Sweetening agents: For chewable tablets: Sugar, mannitol. Saccharine (artificial): 500 time’s sweeter than sucrose Disadvantage: Bitter aftertaste and carcinogenic Aspartame (artificial) Disadvantage: Lack of stability in presence of moisture.

18. Why granulation Improving flow and compression characteristics, Improving content uniformity, Reducing segregation, Facilitating metering or volumetric dispensing, Controlling/manipulating release rate, Eliminating generation of excessive amounts of fine particles thereby increasing bulk density of the product.

19. ADVANTAGES Improves flowability and compressibility of the material Bioavailability improves as hydrophobic surfaces gets changed into hydrophilic surfaces Fast method to prepare controlled release granules Improves homogeneity of dosage forms with low active content Adverse influence of poor electrostatic properties of powder can be avoided

20. DISADVANTAGES An expensive process associated with requirement for more labour , space, time, special equipment and energy Involves multiple processing steps thereby increases complexity Process loss of material is high Unsuitable for moisture sensitive, thermolabile , and incompatible materials Any incompatibility between the formulation components is aggravated during the processing.

21. Mechanisms of particle-particle interactions during Granulation Solid bridges: formed due to solvent evaporation in the drying phase (partial melting, hardening binders or crystallization of dissolved substances) Adhesion and cohesion forces in the Immobile liquids between individual particles. Interfacial forces in mobile liquids films within the granules Intermolecular and long-range forces: vander Waals forces, electrostatic forces results in bonding of the particles. Mechanical interlocking: fracture and deformation due to pressure that results in shape related bonding or intertwining of long fibrous particles.

22. Pendular State : This state usually occurs at low moisture level. In this state the particles are held together by lens shaped rings of liquid. It causes adhesion due to lowering of the surface tension forces at the liquid air interface and the hydrostatic suction pressure in the liquid bridge. 

23. Funicular State: This state represents an intermediate stage between the pendular and capillary states. When the air starts to displace from between the particles, the particles arrange in funicular state. After the funicular state, the particle arrange themselves in capillary state and there is no air between them.

24. Capillary State: When all the air has been displaced from between the particles the capillary state is reached, and the particles are held by capillary suction at the liquid-air interface, which is now only at the granule surface. Moist granule tensile strength increases about three times between the pendular and the capillary state. It may appear that the state of the powder bed is dependent upon the total moisture content of the wetted powders, but the capillary state may also be reached by decreasing the separation of the particles. This state is the most desirable state in the process of granulation. 

25. Droplet state Strength of droplet depends upon the surface tension of liquid used.

26. Mechanisms of Granule Formation a) Nucleation-Granulation starts with particle-particle contact and adhesion due to liquid bridges. A number of particles will join to form the pendular state. Further agitation densifies the pendular bodies to form the capillary state, and these bodies act as nuclei for further granule growth. b) Transition-Nuclei can grow in two possible ways: either single particles can be added to the nuclei by pendular bridges, or two or more nuclei may combine. The combined nuclei will be reshaped by the agitation of the bed. This stage is characterized by the presence of a large number of small granules with a fairly wide size distribution.

27. c) Ball Growth-If agitation is continued, granule coalescence will continue and produce an unusable, over-massed system, although this is dependent upon the amount of liquid added and the properties of the material being granulated

28. Oscillatory granulator Planetary mixer

29. Chilsonator roller

30. Defects in tableting Capping and Lamination Picking and sticking Weight variation Granule size and size distribution before compression Poor flow and Poor mixing Mottling Punch variation Hardness variation Double impression