dds-lec-mid.pdf
Transcript
TABLETS -are prepared by subjecting the fill material to solid dosage forma usually prepared with the aid more than a single compression. of suitable pharmaceutical excipients -The result may be a multiple-layer tablet or a -are p...
TABLETS -are prepared by subjecting the fill material to solid dosage forma usually prepared with the aid more than a single compression. of suitable pharmaceutical excipients -The result may be a multiple-layer tablet or a -are prepared primarily by compression, with a tablet within a tablet, the inner tablet being the limited number prepared by molding. core and the outer portion being the shell. -Some tablets are scored, or grooved, which -Layered tablets are prepared by initial allows them to be easily broken Into two or more compaction of a portion of fill material in a die parts. This enables the patient to swallow smaller followed by additional fill material and portions as may be desired, or when prescribed, it compression to form two-layered or three- layered allows the tablet to be talien in reduced or divided tablets, depending on the number of separate fills. dosage -Each layer may contain a different medicinal agent, separated for reasons of chemical or physical incompatibility, staged drug release, or TYPES OF TABLETS simply the unique appearance of the layered tablet. 1. COMPRESSED TABLETS - Diluents or fillers, which add the necessary bulk to a formulation to 1.2 SUGAR COATED TABLETS prepare tablets of the desired size -Compressed tablets may be coated with a colored or an uncolored sugar layer, water soluble Binders or adhesives, which promote adhesion of and quickly dissolves after swallowing. the particles of the formulation, allowing a granulation to be prepared and maintaining the integrity of the final tablet The sugarcoat: -protects the enclosed drug from the environment and provides a barrier to objectionable taste or Disintegrants or disintegrating agents, which odor. promote breakup of the tablets after - enhances the appearance of the compressed administration to smaller particles for ready drug tablet and permits imprinting of identifying availability manufacturer's information. Antiadherents, glidants, lubricants, or lubricating DISADVANTAGE: agents, which enhance the flow of the material - Sugarcoating may add 50% to the weight and into the tablet dies, minimize wear of the punches bulk of the uncoated tablet. and dies, prevent fill material from sticking to the punches and dies, and produce tablets with a sheen ( for machine, para nindot ang pag kuan sa 1.3 FILM COATED TABLETS machine) -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 Miscellaneous adjuncts such as colorants and over sugarcoatings in that it is more durable, less flavorants bulky, and less time-consuming to apply. -the coating is designed to rupture and expose the After compression, tablets may be coated with core tablet at the desired location in the various materials as described later Tablets for gastrointestinal tract. oral, buccal, sublingual, or vaginal administration may be prepared by compression. 1.4 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 1.1 MULTIPLE-COMPRESSED TABLETS capsule filled with an equivalent amount of powder. gelatin-coated tablets are more tamper evident than unsealed capsules. TYPES OF TABLETS Ex: Tylenol Cold Multi Symptom Daytime (McNeil Consumer) 2. MOLDED TABLETS - Certain tablets, such as talilet triturates, may be prepared by molding rather than by compression 1.5 ENTERIC COATED TABLETS -The resultant tablets are very soft and soluble -have delayed-release features. and are designed for rapid dissolution. -designed to pass unchanged through the -The mold is made of hard rubber, hard plastic, or stomach to the intestines. metal it has two parts, the upper part, or die -are employed when the drug substance is portion, and the lower part, containing squat, flat destroyed by gastric acid or is particularly irritating punches. to the gastric mucosa or when bypass of the -Molded tablets are intended to dissolve rapidly in stomach substantially enhances drug absorption the mouth. They do not contain disintegrants, lubricants, or coatings to slow their rate of dissolution 1.6 BUCCAL AND SUBLINGUAL TABLETS -are flat, oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the TABLET TRITURATES tongue (sublingual tablets) for absorption through -are small, usually cylinderal, morded, or oral mucosa. compressed tablets containing small amounts of -enable oral absorption of drugs that are usually potent drugs destroyed by the gastric juice and/or are poorly -Today, only a few tablettiturate products are absorbed from the gastro intestinal tract. available commercially, with most of these -Buccal tablets are designed to erode slowly produced by tablet compression sublingual use (such as nitroglycerin [NTG]) -tablet triturates must be readily and Completely dissolve promptly and provide rapid drug effects soluble in water, only a minimal amount of pressure is applied during their manufacture -A combination of sucrose and lactose is ustrelly 1.7 CHEWABLE TABLETS the diluent -have a smooth, rapid disintegration when shewed or allowed to dissolve in the mouth have a creamy base, usually of specially flavored and colored HYPODERMIC TABLETS mannitol -originally used by physicians in extemporaneous -useful for administration of large tablets to preparation of parenteral solutions children and adults who have difficulty swallowing -required number of tablets was dissolved in a solid dosage farms suitable vehicle, sterility attained, and the injection -Generally, chewable tablets do not contain performed. disintegrants, so patients must be counseled to -However, the difficulty in achieving sterility and chew the tablets thoroughly and not swallow them the availability of prefabricated injectable products, whole some in disposable syringes, have eliminated the Mannitol, a white crystalline hexahydric alcohol, need for hypodermic tablets is used as the excipient in most chewable tablets, commonly used as excepients DISPENSING TABLETS/COMPOUNDING TABLETS 1.8 EFFERVESCENT TABLETS -the pharmacist used them to compound -prepared by compressing granular effervescent prescriptions; they were not dispensed as such to salts that release gas when in contact with the patient. medicinal substances that dissolve rapidly when -tablets contained large amounts of highly potent added to water drug substances, so the pharmacist could rapidly -The "bubble action" can assist in breaking up the obtain premeasured amounts for compounding tablets and enhancing the dissolution of the active multiple dos age units. drug. -had the dangerous potential of being -generally contain inadvertently dispensed as such to patients IMMEDIATE RELEASE TABLETS VAGINAL TABLETS/VAGINAL INSERTS -designed to disintegrate and release their -uncoated, bullet-shaped, or ovoid tablets inserted medication with no special rate-controlling into the vagina for local effects. features, such as special coatings and other -prepared by compression and shaped to fit techniques. snugly on plastic inserter devices that accompany the product. RAPIDLY DISINTEGRATING/DISSOLVING TABLETS Quality Standards and Compendial -characterized by disintegrating or dissolving in Requirements the mouth within 1 minute, some within 10 seconds. -designed for children and the elderly or for any Tablet Weight and USP Weight Variation Test patient who has difficulty in swallowing tablets -The USP contains a test for determination of -They liquefy on the tongue, and the patient dosage form uniformity by weight variation for swallows the liquid. uncoated tablets. -In the test, 10 tablets are weighed individually, and the average weight is calculated. RAPIDLY DISINTEGRATING/DISSOLVING TABLETS Techniques in Preparation: Content Uniformity Lyophilization -By the USP method, 10 dosage units are Soft direct compressions individually assayed for their content - requirements for content uniformity are met if the amount of active ingredient in each dosage unit -These RDTs are more convenient to carry and lies within the range of 85% to 115% of the label administer than an oral liquid. claim and the standard deviation is less than 6% -They are generally packaged in cards or bubble- type packaging with each individual tablet in its own cavity Quality standards and Compendial Requirements DISANDVANTAGES: drug loading, taste masking, friability, Tablet Thickness manufacturing costs, and stability of the product. -is determined by the diameter of the die, the amount of fill permitted to enter the die, the compaction characteristics of the fill material, and RAPIDLY DISINTEGRATING/DISSOLVING the force or pressure applied during compression. TABLETS -The degree of pressure affects not only thickness Lyophilized Foam but also hardness of the tablet; hardness is perhaps the more important criterion since it can -The first entry into the RDT field was the Zydis affect disintegration and dissolution. delivery system. -Tablet thickness may be measured by hand -The tablets are prepared by foaming a mixture of gauge during production or by automated gelatin, sugar or sugars, drug, and any other equipment components and by pouring the foam into a mold. -This system is the fastest disintegrating system Quality standards and Compendial on the market, as the tablets will dissolve on the Requirements tongue in a matter of a few seconds Tablet Hardness and Friability EXTENDED RELEASE/CONTROLLED -common for a tablet press to exert as little as RELEASE TABLETS 3,000 and as much as 40,000 lb of force in the -are designed to release their medication in a production of tablets. predetermined manner over an extended period. -the greater the pressure applied, the harder the -are tested in simulated gastric fluid for 1 hour, tablets, although the characteristics of the after which no sign of disintegration, cracking, or granulation also have a bearing on hardness. softening must be seen. -lozenges and buccal tablets, that are intended to -They are then actively immersed in the simulated dissolve slowly are intentionally made hard; other intestinal fluid for the time stated in the individual tablets, such as those for immediate drug release, monograph, during which time the tablets are made soft. disintegrate completely for a positive test -A tablet's durability may be determined through the use of a friabilator Quality standards and Compendial Requirements Quality standards and Compendial Requirements Tablet Dissolution -The goal of in vitro dissolution testing is to Tablet Hardness and Friability provide insofar as is possible a reasonable prediction of or correlation with the product's in vivo bioavailability Friability-tendency to crumble. -The system relates combinations of a drug's solubility (high or low) and its intestinal -The tablets are weighed before and after a permeability (high or low) as a possible basis for specified number of rotations, and any weight loss predicting the likelihood of achieving a successful is determined. in vivo-in vitro correlation (IVIVC) -Resistance to loss of weight indicates the tablet's -Using this system, drugs are placed into one of ability to withstand abrasion in handling, four categories as follows: packaging, and shipment -A maximum weight loss of not more than 1% 1-High solubility and high permeability generally is considered acceptable for most Il-Low solubility and high permeability products III-High solubility and low permeability IV-Low solubility and low permeability Quality standards and Compendial Requirements Vitro - for laboratory Tablet Disintegration. Vivo- animals,. -All USP tablets must pass a test for disintegration, Manufacture of Compressed Tablets which is conducted in vitro using a testing wet granulation apparatus dry granulation -Complete disintegration is defined as "that state direct compression in which any residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus is a soft mass TABLETS GRANULATION having no palpably firm core -Tablets must disintegrate within the times set forth in the individual monograph. usually 30 Tablet Granulation: is the process in which small minutes, but varying from about 2 minutes for powder particles adhere together by forming NTG tablets to up to 4 hours for buccal tablets. bonds between them, resulting in the formation of large aggregates called granules. The bonds are formed either by compression or by using binding Quality standards and Compendial agents. Requirements Tablet Disintegration IMPORTANCE OF TABLET GRANULATION Enteric-coated tablets Even though powders are present, granules are prepared due to the following reasons :- Disadvantage selection of excipients is highly restricted due to less inherent binding property in To avoid particle separation in powders, due to most of the excipients, low dose of drugs will not their different size, be uniformly mixed, excipients for direct compression are expensive and they also have a shape and densities. problem of interaction with drug substances Enhance the flow property. Higher flow ability WET GRANULATION gives better filling of dies or containers. Wet or Moist granulation is the most conventional, ✓ Improves compressibility of powders. versatile, and widely used techniques for the ✔Materials that are hygroscopic may adhere and manufacture of compressed tablets. form a cake if storedas a powder. -This technique involves the usage of liquid to form compact masses, Wet granulation involves ✔Granulation of toxic materials will reduce the the following steps:- hazard of generation of toxic dust, which may -Weigh, sift and mix of drug substance and arise during the handling of powders.DIRECT excipients excluding lubricants in an appropriate COMPRESSION mixer to get uniform powder mix. -A damp mass is prepared from the powder mix using a binder solution. Insufficient binder causes Direct compression is a dry process where in the poor adhesion leading to soft tablets. Excessive powdered material is compressed directly into the binder solution yields hard tablets with slower tablets without the physical nature of the powder disintegration rate. being modified Wet granules are dried in an hot air oven at 60°C. Direct Compression involves the following steps:- The drying temperature and drying time are carefully observed. Weigh and grind the ingredients (active ✔Dried granules are passed through Sieve 20 to ingredients and excipients). get uniform size granules. Mixing of active ingredients with powdered Appropriate amount of lubricants is mixed with excipients including the lubricants and glidants. granules. The remaining amount of disintegrants are also added at this stage. ✓Compression of mixed powders in a tablet press. ✔Mixed granules are compressed in a single on multi-punch station tablet press fitted with Diluent - spray dried lactose, mannitol appropriate punches and dies. Disintegrants - tale DRY GRANULATION Dry or Double compression is used to form granules without using a liquid solution because Lubricants-magnesium stearate the product to be granulated may be sensitive to moisture and heat. Glidants - talc, colloidal silica The techniques of dry granulation of powdered Advantages - lewer processing steps, less material can be accomplished by two methods :- equipment, less expensive. no involvement of moisture and heat, faster dissolution rate, chance 1. Slugging - formation of extra large tablets first, of transfer losses, and lesser equipment then broken into granules, which are again contamination. recompressed. 2. Roller compaction method achieved by feeding powder through a set of directly opposed counter rotating rollers. TABLET COATING METHODS SUGARCOATING (c) smoothing and final rounding Dry granulation involves the following steps: -After the tablets are sub coated, 5 to 10 Appropriate quantities of ingredients and additional coatings of a thick syrup are applied to excipients are weighed on an analytical balance. complete the rounding and smooth the coatings ✔Ingredients are mixed in a powder mixer until a (d) finishing and coloring if desired unifoun powder mix is achieved. The half quantity - To attain final smoothness and the appropriate of lubricant is added at this stage to enhance color to the tablets, several coats of a thin syrup powder flow and to prevent sticking of powder to containing the desired colorant are applied in the die. usual manner. -Mixed ingredients are compressed into flat large (e) polishing tablets called slug. This is called pre-compression or slugging. TABLET COATING METHODS IMPRINTING ✔Slugs are broken into smaller pieces using an appropriate miller. Milled slugs are sieved to produce uniform granules. -Solid dosage forms may be passed through a special imprinting machine to impart identification codes and other distinctive symbols. Technically, After sieving, remaining lubricants and excipients the imprint may be: are incorporated mto granules and mixed to form -Debossed means imprinted with a mark below a uniform blend, the surface -Embossed means imprinted with a mark raised Mixed uniform blend of granules are compressed above the sur face into tablet using the tablet press. -Engraved means imprinted with a code that is cut into the surface during production TABLET COATING METHODS SUGARCOATING TABLET COATING METHODS (a) waterproofing and sealing if needed FILM-COATING (b) Subcoating -which places a thin, skin-tight coating of a plastic- (c) smoothing and final rounding like material over the compressed tablet, was (d) finishing and coloring if desired developed to produce coated tablets having (e) polishing essentially the same weight, shape, and size as the originally compressed tablet. -are far more resistant to destruction by abrasion TABLET COATING METHODS than are sugarcoated tablets. SUGARCOATING (a)waterproofing and sealing if needed TABLET COATING METHODS ENTERIC-COATING For tablets containing components that may be -usually an enteric coating is based on factors of adversely affected by moisture, one or more coats pH, resisting dissolution in the highly acid of a waterproofing substance, such as environment of the stomach but yielding to the pharmaceutical shellac, or a polymer, are applied less acid environment of the intestine. to the compressed tablets before the subcoating -Some enteric coatings are designed to dissolve application at pH 4.8 and greater. -The coating system may be aqueous or organic solvent based and effective so long as the coating (b) Subcoating material resists breakdown in the gastric fluid. After the tablets are waterproofed if needed, three -Among the materials used in enteric coatings are to five subcoats of a sugar-based syrup are pharmaceutical shellac, hydroxypropyl applied. This bonds the sugar coating to the tablet methylcellulose phthalate, polyvinyl acetate and provides rounding. phthalate, diethyl phthalate, and cellulose acetate phthalate. PACKAGING AND STORAGE OF TABLETS -Tablets are stored in tight containers, in 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. -In dispensing tablets, the pharmacist is well advised to use a similar type of container as provided by the manufacturer of the product PACKAGING AND STORAGE OF TABLETS rapidly dissolving tablets tend to be softer than regular compressed immediate release tablets and require special packaging.
