TABLETS.pptx

Tablet dosage forms

1. TABLET DOSAGE FORM

2. Introduction Tablets are solid dosage forms consisting of active ingredient(s) and suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics, and in other aspects. They may be class yfied , according to the method of manufacture, as compressed tablets or molded tablets.

3. Traditionally, tablets have been made by granulation, a process that imparts two primary requisites to formulate: compactibility and fluidity. Both wet granulation and dry granulation (slugging and roll compaction) are used. Numerous unit processes are involved in making tablets, including particle size reduction and sizing, blending, granulation, drying, compaction, and (frequently) coating.

4. Advantages They are unit dosage forms hence precise dose delivery and least content variability. They are economic amongst oral dosage forms. They are lightest and most compactable. They are easily packed and equally economical. Product identification is simpler.

5. Self administration by the patient can be achieved. They lend themselves to certain release profile, like Enteric, sustained release products. They have best combined properties of chemical, mechanical and microbiologic stability of all the oral forms.

6. Disadvantages Some drugs resist compression into dense compacts Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating

7. Types of tablets C ompressed T ablets S ugar coated T ablets F ilm coated T ablets E nteric coated T ablets E ffervescent T ablets C hewable T ablets D ispersible T ablets S ustained release T ablets M ultilayer T ablets S ublingual T ablets T roches B uccal T ablets I mplant T ablets H ypodermic T ablets S olution T ablet s V aginal T ablets

8. Tablet design and Formulation The main objective of the design and manufacture of the compressed tablets, deliver oral correct amount of the drug, in proper form, at proper time and in desired location and to have its chemical integrity protected to that point.

9. Characteristics of ideal tablet It should be elegant. It should have strength to withstand mechanical shocks during various processes. It should have physical and chemical stability. It should be able to release medicinal agents in predictable and reproducible manner.

10. Formulation components Formulation components attribute towards: Provide essential manufacturing technology functions ( Binders, lubricants, glidants ) Modify drug release ( Disintegrants, polymers ) Enhance stability ( Antioxidants ) Enhance patient acceptance ( Flavors, Colors ) All non drug components of a formula are termed as EXCIPIENTS .

11. Characteristics of ideal Excipient They must be nontoxic and acceptable to regulatory agencies. 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.

12. Excipients Diluent Binder and adhesive Disintegrents Lubricants and glidants Coloring agents Flavoring agents Sweetening agents

13. Diluents 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.

14. 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 Dextrose

15. Binders and Adhesives Binders promote the adhesion of particles of the formulation. Such adhesion enables preparation of granules and maintains the integrity of the final tablet.

16. Commonly used tablet binders 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 Sodium alginate Sorbitol

17. Disintegrants The breakup of the tablets to smaller particles is important for dissolution of the drug & subsequent bioavailability. Disintegrators promote such breakup. To rupture or breakup of tablets, disintegrating agents must swell or expand on exposure to aqueous solution. Thus, the most effective disintegrating agents in most tablet systems are those with the highest water uptake property. In general, the more hydrophilic, the better disintegrating agents are therefore highly hydrophilic.

18. Commonly used tablet disintegrants Starch‐ 5‐20% of tablet weight. Starch derivative – Primogel and Explotab (1‐8%) Clays‐ Veegum HV, bentonite 10% level in colored tablet only Cellulose Cellulose derivatives‐ Ac‐ Di‐Sol (sodium carboxy methyl cellulose) Alginate PVP ( Polyvinylpyrrolidone ), cross‐linked

19. Lubricants and Glidants Lubricant is a substance capable of reducing or preventing friction, heat, and wear when introduced as a film between solid surfaces. It works by coating on the surface of particles, and thus preventing adhesion of the tablet material to the dies and punches. Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles.

20. Commonly used tablet lubricant and Glidants 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.

21. Coloring agents (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.

22. Commonly used tablet colorants 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 & Cred 3‐ Erythrosine. D & Cred 22 – Eosin Y

23. Flavors and sweeteners Flavoring agents: For chewable tablet‐ flavor oil are used 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.

24. Tablet Manufacturing Granulation Technology

25. Chlisonator Roller compactor

26. Wet Granulation Mechanism There are five primary bonding mechanisms between particles: Adhesion and cohesion forces in the immobile liquid films between individual primary powder particles; Surface tension and negative capillary pressure Interfacial forces in mobile liquid films within the granules; Coalesce Capillary stage interfacial forces The formation of solid bridges after solvent evaporation; Attractive forces between solid particles; Mechanical interlocking. .

27. Diosna Granulator

28. Tablet compression Machines Tablets are made by compressing a formulation containing a drug or drugs with excipients on stamping machine called presses. Tablet presses are designed with following basic components: 1) Hopper for holding and feeding granulation 2) Dies that define the size and shape of the tablet. 3) Punches for compressing the granulation within the dies. 4) Cam tracks for guiding the movement of the punches. 5) A feeding mechanism for moving granulation from hopper into the dies

29. Compression cycle of rotary press

30. Evaluation of Tablets 1. General Appearance: The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lot‐to‐lot uniformity and tablet‐to‐tablet uniformity. The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc. 2. Size & Shape: It can be dimensionally described & controlled. The thickness of a tablet is only variables. Tablet thickness can be measured by micrometer or by other device. Tablet thickness should be controlled within a ± 5% variation of standard value. 3. Unique identification marking: These marking utilize some form of embossing, engraving or printing. These markings include company name or symbol , product code, product name etc. 4. Organoleptic properties: Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against standard color. 5. Hardness and Friability: Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shakes of handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength

31. 6.Friability: Friability of a tablet can determine in laboratory by Roche friabilator . This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator , which is then operate for 100 revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable.

32. Drug Content and Release Uniformity of Weight of Single-Dose Preparations Weigh individually 20 units selected at random or, for single dose preparations in individual containers, the contents of 20 units, and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in the table and none deviates by more than twice that percentage

33. Dosage form Average weight Percentage deviation Uncoated and film- coated tablets 80 mg or less 10 More than 80 mg but less than 250 mg 7.5 250 mg or more 5 Capsules, granules and powders (single-dose) Less than 300 mg 10 300 mg or more 7.5 Powders for parenteral Use More than 40 mg 10 Pessaries and suppositories All weights 5

34. Uniformity of Content for Single-Dose Preparations The test for uniformity of content of single-dose preparations is based on the assay of the individual contents of active substance(s) of a number of single-dose units to determine whether the individual contents are within limits set with reference to the average content of the sample. Method . Determine the content of active ingredient(s) in each of 10 dosage units taken at random using the method given in the monograph or by any other suitable analytical method. Acceptance limits The tablets comply with the test if not more than one of the individual values thus obtained is outside the limits 85 to 115% of the average value and none is outside the limits 75 to 125% of the average value. If two or three of the individual values are outside the limits 85 to 115% of the average value and none is outside the limits 75 to 125%, repeat the determination using another 20 tablets. The tablets comply with the test if in the total sample of 30 tablets not more than three of the individual values are outside the limits 85 to 115% and none is outside the limits 75 to 125% of the average value.

35. Disintegration

36. Dissolution Two objectives in development of invitro dissolution tests are to show That drug release is as close as possible to 100% , and That the rate of drug release is uniform batch to batch.

37. Acceptance Limits according to USP

38. Processing Problems Capping and Lamination 1. Capping and lamination have in the past been attributed to air entrapment during compression process, and does not escape until compression force is removed. 2. However researches revealed that Capping and lamination are due to deformational properties of the formulation.

39. THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘FORMULATION’ (GRANULATION) Sno CAUSES REMEDIES 1 Large amount of fines in the granulation Remove some or all fines through 100 to 200 mesh screen 2 Too dry or very low moisture content (leading to loss of proper binding action). Moisten the granules suitably. Add hygroscopic substance e.g.: Sorbitol, Methylcellulose or PEG-4000. 3 Not thoroughly dried granules. Dry the granules properly. 4 Insufficient amount of binder or improper binder. Increasing the amount of binder OR Adding dry binder such as pre-gelatinized Starch, Gum acacia, powdered Sorbitol, PVP, hydrophilic Silica or powdered Sugar. 5 Insufficient or improper lubricant. Increase the amount of lubricant or change the type of lubricant. 6 Granular mass too cold to compress firm. Compress at room temperature.

40. THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS) Sr. No. CAUSES REMEDIES 1. Poorly finished dies Polish dies properly. Investigate other steels or other materials. 2. Deep concave punches or beveled-edge faces of punches. Use flat punches. 3. Lower punch remains below the face of die during ejection. Make proper setting of lower punch during ejection. 4. Incorrect adjustment of sweep-off blade. Adjust sweep-off blade correctly to facilitate proper ejection. 5. High turret speed. Reduce speed of turret (Increase dwell time).

41. Picking and sticking Picking is a term used to describe the surface material from a tablet that is sticking to and being removed from the tablet’s surface by a punch. Sticking refers to tablet material adhering to die wall.

42. THE CAUSES AND REMEDIES OF PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) Sr. No. CAUSES REMEDIES 1. Rough or scratched punch faces. Polish faces to high luster. 2. Embossing or engraving letters on punch faces such as B, A, O, R, P, Q, G. Design lettering as large as possible. Plate the punch faces with chromium to produce a smooth and non-adherent face. 3. Bevels or dividing lines too deep. Reduce depths and sharpness. 4. Pressure applied is not enough; too soft tablets. Increase pressure to optimum.

43. THE CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION) Sr. No. CAUSES REMEDIES 1. Granules not dried properly. Dry the granules properly. Make moisture analysis to determine limits. 2. Too little or improper lubrication. Increase or change lubricant. 3. Too much binder Reduce the amount of binder or use a different type of binder. 4. Hygroscopic granular material. Modify granulation and compress under controlled humidity. 5. Oily or way materials Modify mixing process. Add an absorbent.

44. Sr. No. CAUSES REMEDIES 1. A coloured drug used along with colourless or white- coloured excipients. Use appropriate colourants . 2. A dye migrates to the surface of granulation while drying. Change the solvent system, Change the binder, Reduce drying temperature and Use a smaller particle size. 3. Improperly mixed dye, especially during ‘Direct Compression’. Mix properly and reduce size if it is of a larger size to prevent segregation. 4. Improper mixing of a coloured binder solution. Incorporate dry colour additive during powder blending step, then add fine powdered adhesives such as acacia and tragacanth and mix well and finally add granulating liquid. Mottling Unequal distribution of color on a tablet, with light or dark spots.

45. Weight Variation The weight of tablet being compressed is determined by the amount of granulation in the die prior to the compression. Therefore anything that can alter the die filling process can alter tablet weight. Granule size and size distribution before compression, Poor mixing and Poor flow, Punch variation

46. Hardness variation Hardness variation is a problem that has the same causes as weight variation, hardness depends on weight of the material and space between the punches at the moment of compression. If volume of the material or distance between punches varies, hardness is likewise inconsistent.

47. Double Impression This involves only punches that have monogram or other engraving on them. Mostly in when two compression stages to compress a tablet.