Tablets Complete_241001_142133.pdf

TABLETS TABLETS solid dosage forms usually prepared with the aid of suitable pharmaceutical excipients vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture...

TABLETS TABLETS solid dosage forms usually prepared with the aid of suitable pharmaceutical excipients vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture TABLETS Prepared by; Compression and Molding Compressed tablets are manufactured with tablet machines capable of exerting great pressure in compacting the powdered or granulated material TABLETS Molded tablets are prepared on a large scale by tablet machinery or on a small scale by manually forcing dampened powder material into a mold from which the formed tablet is then ejected and allowed to dry. TABLETS Some tablets are scored, or grooved and some are not TYPES OF TABLETS 1. Compressed tablets Contain: ▪ Diluents or fillers, which add the necessary bulk to a formulation to prepare tablets of the desired size ▪ Binders or adhesives, which promote adhesion of the particles of the formulation, allowing a granulation to be prepared and maintaining the integrity of the final tablet ▪ Disintegrants or disintegrating agents, which promote breakup of the tablets after administration to smaller particles for ready drug availability 1. Compressed tablets ▪ Antiadherents, glidants, lubricants, or lubricating agents, which enhance the flow of the material into the tablet dies, minimize wear of the punches and dies, prevent fill material from sticking to the punches and dies, and produce tablets with a sheen ▪ Miscellaneous adjuncts such as colorants and flavorants Tablets for oral, buccal, sublingual, or vaginal administration may be prepared by compression. 2. Multiple Compressed Tablets ▪ Prepared by subjecting the fill material to more than a single compression ▪ May be a multiple- layer tablet or a tablet within a tablet, the inner tablet being the core and the outer portion being the shell 2. Multiple Compressed Tablets ▪ Each layer may contain a different medicinal agent, separated for reasons of chemical or physical incompatibility, staged drug release, or simply the unique appearance of the layered tablet ▪ In preparation of tablets within tablets, special machines are required to place the preformed core tablet precisely within the die for application of surrounding fill material  3. Sugarcoated tablets ▪ Compressed tablets may be coated with a colored or an uncolored sugar layer. ▪ The coating is water soluble and quickly dissolves after swallowing. ▪ The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor. ▪ The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturer's information.  3. Sugarcoated tablets ▪ Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size, weight, and shipping costs. ▪ Sugarcoating may add 50% to the weight and bulk of the uncoated tablet.  4. Film-Coated tablets ▪ Compressed tablets coated with a thin layer of a polymer capable of forming a skin-like film. ▪ The film is usually colored and has the advantage over sugarcoatings in that it is more durable, less bulky, and less time-consuming to apply. ▪ By its composition, the coating is designed to rupture and expose the core tablet at the desired location in the gastrointestinal tract.  5. Gelatin-coated tablets ▪ The innovator product, the gelcap, is a capsule-shaped compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder. ▪ The gelatin coating facilitates swallowing, and gelatin- coated tablets are more tamper evident than unsealed capsules. ▪ Examples include Tylenol Cold Multi- Symptom Daytime (McNeil Consumer).  6. Enteric-coated tablets ▪ Have delayed-release features ▪ They are designed to pass unchanged through the stomach to the intestines, where the tablets disintegrate and allow drug dissolution and absorption and/or effect. ▪ Enteric coatings are employed when the drug substance is destroyed by gastric acid or is particularly irritating to the gastric mucosa or when bypass of the stomach substantially enhances drug absorption. 7. Buccal and Sublingual tablets ▪ Buccal and sublingual tablets are flat, oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa. ▪ They enable oral absorption of drugs that are destroyed by the gastric juice and/or are poorly absorbed from the gastrointestinal tract. 7. Buccal and Sublingual tablets ▪ Buccal tablets are designed to erode slowly ▪ Sublingual tablets (such as nitroglycerin [NTG]) dissolve promptly and provide rapid drug effects. ▪ Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a flavoring substance in a hard candy or sugar base. ▪ They are intended to be slowly dissolved in the oral cavity, usually for local effects, although some are formulated for systemic absorption.  8. Chewable Tablets ▪ Have a smooth, rapid disintegration when chewed or allowed to dissolve in the mouth, have a creamy base, usually of specially flavored and colored mannitol. ▪ Useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms.  9. Effervescent tablets ▪ Prepared by compressing granular effervescent salts that release gas when in contact with water. ▪ Generally contain medicinal substances that dissolve rapidly when added to water. ▪ The “bubble action” can assist in breaking up the tablets and enhancing the dissolution of the active drug.  10. Molded tablets ▪ Certain tablets, such as tablet triturates, may be prepared by molding rather than by compression. ▪ The resultant tablets are very soft and soluble and are designed for rapid dissolution.  11. Tablet Triturates ▪ Small, usually cylindrical, molded, or compressed tablets containing small amounts of usually potent drugs ▪ A combination of sucrose and lactose is usually the diluent. ▪ The few tablet triturates that remain are used sublingually, such as NTG tablets. ▪ Pharmacists also employ tablet triturates in compounding. For example, triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances.  12. Hypodermic tablets ▪ Originally used by physicians in extemporaneous preparation of parenteral solutions. ▪ The required number of tablets was dissolved in a suitable vehicle, sterility attained, and the injection performed. ▪ The tablets were a convenience, since they could be easily carried in the physician's medicine bag and injections prepared to meet the needs of the individual patients. ▪ However, the difficulty in achieving sterility and the availability of prefabricated injectable products, some in disposable syringes, have eliminated the need for hypodermic tablets.  12. Hypodermic tablets ▪ Originally used by physicians in extemporaneous preparation of parenteral solutions. ▪ The required number of tablets was dissolved in a suitable vehicle, sterility attained, and the injection performed. ▪ The tablets were a convenience, since they could be easily carried in the physician's medicine bag and injections prepared to meet the needs of the individual patients. ▪ However, the difficulty in achieving sterility and the availability of prefabricated injectable products, some in disposable syringes, have eliminated the need for hypodermic tablets. 12. Hypodermic tablets 13. Immediate-Release tablets ▪ Designed to disintegrate and release their medication with no special rate-controlling features, such as special coatings and other techniques. 14. Rapidly Disintegrating or Dissolving Tablets ▪ Rapid-release tablets (rapidly dissolving tablets or RDTs) are characterized by disintegrating or dissolving in the mouth within 1 minute, some within 10 seconds ▪ Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets. They liquefy on the tongue, and the patient swallows the liquid. ▪ There are no standards that define an RDT, but one possibility is dissolution in the mouth within approximately 15 seconds; anything slower would not be categorized as rapidly dissolving.  15. Extended-Release tablets ▪ Designed to release their medication in a predetermined manner over an extended period 16. Vaginal tablets ▪ Vaginal inserts, are uncoated, bullet-shaped, or ovoid tablets inserted into the vagina for local effects. ▪ They are prepared by compression and shaped to fit snugly on plastic inserter devices that accompany the product. COMPRESSED TABLETS Compendial requirements factors that must be controlled or during production (in-process ▪ controls) and verified after the production of each batch to ensure that established product quality standards are met 1. Weight and weight variation, 2. Content Uniformity, 3. Thickness, 4. Hardness, 5. Disintegration, 6. Dissolution. Compressed Tablets Compendial Requirements 1. Weight Variation - The USP contains a test for determination of dosage form uniformity by weight variation for uncoated tablets. In the test, 10 tablets are weighed individually, and the average weight is calculated. The tablets are assayed, and the content of active ingredient in each of the 10 tablets is calculated assuming homogeneous drug distribution. Compressed Tablets Compendial Requirements 2. Content Uniformity- By the USP method, 10 dosage units are individually assayed for their content according to the method described in the individual monograph. Unless otherwise stated in the monograph, the requirements for content uniformity are met if the amount of active ingredient in each dosage unit lies within the range of 85% to 115%. Compressed Tablets Compendial Requirements 3. Tablet Thickness - for tablets of uniform thickness and hardness, it is doubly important to control pressure. Tablet thickness may be measured by hand gauge during production or by automated equipment Compressed Tablets Compendial Requirements 4. Tablet Hardness and Friability - Generally, the greater the pressure applied, the harder the tablets, although the characteristics of the granulation also have a bearing on hardness. Certain tablets, such as lozenges and buccal tablets, that are intended to dissolve slowly are intentionally made hard; other tablets, such as those for immediate drug release, are made soft. In general, tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing. Compressed Tablets Compendial Requirements 4. Tablet Hardness and Friability Friabilator – apparatus that determines the tablet's friability, or tendency to crumble, by allowing it to roll and fall within the drum. The tablets are weighed before and after a specified number of rotations, and any weight loss is determined. Compressed Tablets Compendial Requirements 4. Tablet Hardness and Friability Resistance to loss of weight indicates the tablet's ability to withstand abrasion in handling, packaging, and shipment. A maximum weight loss of not more than 1% generally is considered acceptable for most products. Compressed Tablets Compendial Requirements 5. Tablet Disintegration For the medicinal agent in a tablet to become fully available for absorption, the tablet must first disintegrate and discharge the drug to the body fluids for dissolution. Tablet disintegration also is important for tablets containing medicinal agents (such as antacids and antidiarrheals) that are not intended to be absorbed but rather to act locally within the gastrointestinal tract. Compressed Tablets Compendial Requirements 5. Tablet Disintegration The apparatus consists of a basket and rack assembly containing six open- ended transparent tubes of USP- specified dimensions, held vertically upon a 10-mesh stainless steel wire screen. During testing, a tablet is placed in each of the six tubes of the basket, and through the use of a mechanical device, the basket is raised and lowered in the immersion fluid at 29 to 32 cycles per minute, the wire screen always below the level of the fluid. Compressed Tablets Compendial Requirements 6. Tablet Dissolution In vitro dissolution testing of solid dosage forms is important for a number of reasons: 1. It guides formulation and product development toward product optimization. 2. Manufacturing may be monitored by dissolution testing as a component of the overall quality assurance program. 3. Consistent in vitro dissolution testing ensures bioequivalence from batch to batch. 4. It is a requirement for regulatory approval of marketing for products registered with the FDA and regulatory agencies of other countries. New Drug Applications (NDAs) submitted to the FDA contain in vitro dissolution data  COMPRESSED TABLETS COMPENDIAL REQUIREMENTS 1. Weight and weight variation, 2. Content Uniformity, 3. Thickness, 4. Hardness and Friability, 5. Disintegration, 6. Dissolution. Compressed Tablets Manufacture 3 Basic Methods 1. Wet Granulation 2. Dry Granulation 3. Direct Compression Compressed Tablets Manufacture 3 Basic Methods 1. Wet Granulation Steps Required: a. Weighing and Blending b. Preparing the Damp Mass c. Screening the Damp Mass into Pellets or Granules d. Drying the Granulation e. Sizing the Granulation f. Addition of Lubricant and Blending Compressed Tablets Manufacture 1. Wet Granulation a. Weighing and Blending Specified quantities of active ingredient, diluent or filler, and disintegrating agent are mixed by mechanical powder blender or mixer until uniform. Fillers that are most preferred Lactose - because of its solubility and compatibility Microcrystalline cellulose - because of its easy compaction, compatibility, and consistent uniformity of supply Compressed Tablets Manufacture 1. Wet Granulation a. Weighing and Blending Disintegrants that are most preferred (because of their high water uptake and rapid action) Croscarmellose (2%) Sodium starch glycolate (5%) The total amount of disintegrant used is not always added in preparing the granulation. Often a portion (sometimes half) is reserved and added to the finished granulation prior to tablet formation. This results in “double disintegration” of the tablet. Compressed Tablets Manufacture 1. Wet Granulation b. Preparing the Damp Mass A liquid binder is added to the powder mixture to facilitate adhesion of the powder particles. Either a dampened powder formed into granules or a damp mass resembling dough is formed and used to prepare the granulation. A good binder results in appropriate tablet hardness and does not hinder the release of the drug from the tablet. Compressed Tablets Manufacture 1. Wet Granulation b. Preparing the Damp Mass Care must be exercised not to overwet or underwet the powder. Overwetting - result in granules that are too hard for proper tablet formation Underwetting - result in tablets that are too soft and tend to crumble. Compressed Tablets Manufacture 1. Wet Granulation c. Screening the Damp Mass into Pellets or Granules The dampened powder granules are screened, or the wet mass is pressed through a screen (usually 6 or 8 meshes) to prepare the granules. May be done by hand or with special equipment that prepares the granules by extrusion through perforations in the apparatus. Resultant granules - spread evenly on large lined trays and dried to consistent weight or constant moisture content. Compressed Tablets Manufacture 1. Wet Granulation d. Drying the Granulation Granules may be dried in thermostatically controlled ovens that constantly record the time, temperature, and humidity e. Sizing the Granulation by Dry Screening After the wet granules are dried, they are passed through a finer/smaller mesh/screen than the one used during initial granulation. This process reduces the size of the granules to achieve a uniform particle size that suits the tablet size being produced. Compressed Tablets Manufacture 1. Wet Granulation f. Adding Lubricant and Blending Dry lubricant is dusted over the spread-out granulation through a fine-mesh screen and contribute to the preparation of compressed tablets in several ways: ✓ Improve the flow of the granulation in the hopper to the die cavity. ✓ Prevent adhesion of the tablet formulation to the punches and dies during compression. ✓ Reduce friction between the tablet and the die wall during the ejection of the tablet from the machine. ✓ Give a sheen to the finished tablet. Compressed Tablets Manufacture Fluid-Bed Process Fluid-Bed Granulator (a)Pre-blending the formulation powder, including active ingredients, fillers, and disintegrants, in a bed with fluidized air; (b)granulating the mixture by spraying onto the fluidized powder bed, a suitable liquid binder, such as an aqueous solution of acacia, hydroxypropyl cellulose, or povidone; and (c)drying the granulated product to the desired moisture content. Compressed Tablets Manufacture Wet Granulation Steps Required: a. Weighing and Blending b. Preparing the Damp Mass c. Screening the Damp Mass into Pellets or Granules d. Drying the Granulation e. Sizing the Granulation f. Addition of Lubricant and Blending Compressed Tablets Manufacture 2. Dry Granulation ▪ Powder mixture is compacted in large pieces and subsequently broken down or sized into granules ▪ Either the active ingredient or the diluent must have cohesive properties. ▪ Applicable to materials that cannot be prepared by wet granulation because they degrade in moisture or the elevated temperatures required for drying the granules. Compressed Tablets Manufacture 2. Dry Granulation Methods: a. Roller Compaction Powders are compressed between two rollers to form sheets or ribbons, which are then milled into granules. Often preferred to slugging b. Slugging After weighing and mixing the ingredients, the powder mixture is slugged, or compressed, into large flat tablets or pellets about 1 inch in diameter. Compressed Tablets Manufacture 2. Dry Granulation Methods: Compressed Tablets Manufacture 3. Direct Compression Some granular chemicals, like potassium chloride, possess free-flowing and cohesive properties that enable them to be compressed directly in a tablet machine without any need of granulation. For chemicals lacking this quality, special pharmaceutical excipients may be used to impart the necessary qualities for the production of tablets by direct compression. TABLET COATING Sugarcoating Tablet The sugarcoating of tablets may be divided into the following steps: (a)waterproofing and sealing if needed, (b)subcoating, (c)smoothing and final rounding, (d)finishing and coloring if desired, and (e) (e)polishing Sugarcoating Tablet A. Waterproofing and Sealing Coats Pharmaceutical shellac or a Polymer Waterproof substance that is applied to the compressed tablets containing components that may be adversely affected by moisture Sugarcoating Tablet B. Subcoating Three to five subcoats of a sugar-based syrup are applied This bonds the sugar coating to the tablet and provides rounding shape of the tablet. The sugar-based syrup contains: 1. Gelatin 2. Acacia, to enhance coating. Sugarcoating Tablet C. Smoothing and Final Rounding After the tablets are subcoated, 5 to 10 additional coatings of a thick syrup are applied to complete the rounding and smooth the coatings. D. Finishing and Coloring To attain final smoothness and the appropriate color to the tablets, several coats of a thin syrup containing the desired colorant are applied in the usual manner. Sugarcoating Tablet E. Polishing Few Methods: Use special pans lined with cloth soaked in carnauba or beeswax, allowing the tablets to tumble and get a shiny finish. Putting pieces of wax in a pan and letting the tablets roll over them until they shine. Lightly spray the tablets with wax dissolved in a solvent. Film-coating Tablets The film-coating process, which places a thin, skin-tight coating of a plastic-like material over the compressed tablet, was developed to produce coated tablets having essentially the same weight, shape, and size as the originally compressed tablet. Film-coating Tablets Film-coating solutions may be nonaqueous or aqueous. The nonaqueous solutions contain the following types of materials to provide the desired coating to the tablets: 1. Film former - capable of producing smooth, thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes. Example: cellulose acetate phthalate 2. Alloying substance - providing water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug. Example: polyethylene glycol Film-coating Tablets 3. Plasticizer - to produce flexibility and elasticity of the coating and thus provide durability. Example: castor oil 4. Surfactant - to enhance spreadability of the film during application. Example: polyoxyethylene sorbitan derivatives 5. Opaquants and colorants - to make the appearance of the coated tablets handsome and distinctive. Examples: opaquant, titanium dioxide; colorant, FD&C or D&C dyes Film-coating Tablets 6. Sweeteners, flavors, and aromas - to enhance the acceptability of the tablet by the patient. Examples: sweeteners, saccharin; flavors and aromas, vanillin 7. Glossant - to provide luster to the tablets without a separate polishing operation. Example: beeswax 8. Volatile solvent - to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation. Example: alcohol mixed with acetone Enteric Coating Enteric-coated solid dosage forms intended to pass through the stomach intact to disintegrate and release their drug content for absorption along the intestines Material used in enteric coating Pharmaceutical shellac, Hydroxypropyl methylcellulose phthalate, Polyvinyl acetate phthalate, Diethyl phthalate, and Cellulose acetate phthalate PACKAGING AND STORING TABLETS Tablets are stored in: ✓ tight containers, ✓ places of low humidity, and ✓ protected from extremes in temperature. Products that are prone to decomposition by moisture generally are packaged with a desiccant packet. Drugs that are adversely affected by light are packaged in light-resistant containers. PACKAGING AND STORING TABLETS The pharmacist also should caution patients about handling medication when it poses a risk. Finasteride tablets ▪ taken by men to treat benign prostatic hyperplasia (BPH). ▪ Has the potential to harm a male fetus if absorbed by a pregnant woman either through direct contact with finasteride or possibly through semen.