Tablets - University of Southern Mindanao PDF

UNIVERSITY OF SOUTHERN MINDANAO TABLETS  TABLETS ▪ Solid Preparations – one or more active ingredients and are obtained by compressing uniform volumes of particles.  TABLETS - Advantages 1. Offers greatest dose precision and the least content variability 2. Lightest and most /comp...

UNIVERSITY OF SOUTHERN MINDANAO TABLETS  TABLETS ▪ Solid Preparations – one or more active ingredients and are obtained by compressing uniform volumes of particles.  TABLETS - Advantages 1. Offers greatest dose precision and the least content variability 2. Lightest and most /compact of all oral dosage. 3. Best combined properties of chemical, mechanical, microbiologic stability of all the oral forms. 4. Convenience of administration.  TABLETS - disadvantages 1. Drugs resist compression into dense compacts, owing to their amorphous nature of flocculent quality. 2. Poor wetting, dissolution properties – difficult or impossible to formulate and manufacture as a tablet that will provide adequate or full drug bioavailability. 3. Drugs with Bitter-tasting, Objectionable odor, sensitive to oxygen or atmospheric moisture n may require encapsulation or entrapment prior to compression or the tablets may require coating.  COMPRESSED TABLETS (CT) ▪ Types of CT ▪ Sugar-coated tablets (SCT) ▪ Film-coated Tablets (FCT) ▪ Enteric-Coated (ECT) ▪ Multiple Compressed Tablet (MCT) ▪ Layered Tablets ▪ Press-Coated Tablets ▪ Controlled-Release Tablets ▪ Tablets For Solution  COMPRESSED TABLETS (CT) ▪ Types of CT ▪ Effervescent Tablets ▪ Compressed Suppositories or Inserts ▪ Buccal or Sublingual Tablets  COMPRESSED TABLETS (CT) ▪ Sugar-Coated Tablets ▪ Beneficial in covering-up drug substances possessing objectionable tastes or odors, or protecting material sensitive to oxidation.  COMPRESSED TABLETS (CT) ▪ FCT ▪ Covered with thin layer of film of a water-soluble material ▪ A number of polymeric substance with film-forming properties may be used.  COMPRESSED TABLETS (CT) ▪ ECT ▪ Substance that resist solution in gastric fluid but disintegrate in the intestine. ▪ Used for tablets containing drug substances which are inactive or destroyed in the stomach, for those which irritate the mucosa, or as a means of delayed release of the medication.  COMPRESSED TABLETS (CT) ▪ MCT ▪ Layered Tablets ▪ Prepared by compressing tablet granulation. ▪ The operation maybe repeated to produce multilayered tablets of two or three layers ▪ Press-coated Tablets ▪ Referred to as dry-coated ▪ Prepared by feeding previously compressed tablet into a special tableting machine and compressing another granulation layer around the preformed tablets  COMPRESSED TABLETS (CT) ▪ CRT ▪ Prolonged-release or Sustained- release ▪ 3 types 1. Those which respond to some physiological condition to release the drug, such as enteric coating 2. Those that release the drug in relatively steady, controlled manner, and 3. Those that combine combinations of mechanisms to release “pulses” of drugs, such as repeat action tablets.  COMPRESSED TABLETS (CT) ▪ Tablets for Solution ▪ Preparing solutions or imparting given characteristics to solutions must be labeled to indicate that they are not be swallowed. ▪ Example: Halazone Tablets for Solutions or Potassium Permanganate Tablet for solution  COMPRESSED TABLETS (CT) ▪ Effervescent Tablet ▪ tablets.  COMPRESSED TABLETS (CT) ▪ Compressed Suppositories or Inserts ▪ Vaginal Suppositories ▪ Example: Metronidazole Tablets  COMPRESSED TABLETS (CT) ▪ Buccal and Sublingual Tablets ▪ Small ▪ Flat oval tablets ▪ Buccal – Inserting into buccal pouch dissolve or erode slowly ▪ Sublingual – under the tongue ▪ Example: ▪ Progesterone Tablets (Buccal) ▪ Nitroglycerine, Isoproterenol HCl, Erythrityl Tetranitrate  MOLDED TABLETS OR TABLET TRIOTURATES (TT) ▪ Made from moist materials using a triturate mold which gives them shape of cut sectioning of a cylinder ▪ Types ▪ Dispensing Tablets (DT) ▪ Hypodermic Tablets (HT)  PROPERTIES ▪ Freedom from defects such as chips, cracks, discoloration, and contamination ▪ Should have strength to withstand the rigors of the mechanical treatment involved in production, packaging, shipment and dispensing ▪ Should have chemical and physical stability to maintain its physical attributes over time. ▪ Must be able to release the medicament in a reproducible and predictable manner.  COMPONENTS ▪ Essential Components ▪ Compressed Aides ▪ Supplementary Components  COMPONENTS ▪ Essential Components ▪ Diluents or bulking agents ▪ Make up the major portion of the tablet ▪ Lactose USP (Hydrous, Anhydrous) ▪ Coarse Granular: 60-80 mesh ▪ Regular: 80-100 mesh ▪ Spray-dried: 100- 120 mesh  COMPONENTS ▪ Essential Components ▪ Lactose USP (Hydrous, Anhydrous) ▪ Advantages ▪ Inexpensive ▪ Readily Soluble ▪ Stable and Generally inert ▪ Not softened by the frictional forces of compression due to its high melting point (202C)  COMPONENTS ▪ Essential Components ▪ Lactose USP (Hydrous, Anhydrous) ▪ Disadvantages ▪ Binders may have to be added when presence of drugs or some other substance interfere with cohesion. ▪ Lubricants required  COMPONENTS ▪ Essential Components ▪ Lactose Spray-dried Special Advantages ▪ Flow from the Hoppe d/t spherical Granules ▪ Flow property maintain even when wet granulated, provided the particles have not been broken by high- speed grinding ▪ Can be tableted without addition of binders ▪ Used for direct Compression methods  COMPONENTS ▪ Essential Components ▪ Starches ▪ Derived from Wheat, corn, rice, and potato ▪ Used as Binders and Disintegrants ▪ Provide a moisture balance even though moisture content is 12-14%. ▪ Stabilized hygroscopic drugs ▪ Protects tablets from deterioration before use  COMPONENTS ▪ Essential Components ▪ Mannitol (powder/ granular) ▪ Advantages ▪ Highly desirable for water-sensitive drugs ▪ Appropriate for chewable tablets because of its taste and negative heat of solution. ▪Disadvantages ▪ Expensive  COMPONENTS ▪ Essential Components ▪ Sorbitol ▪ Advantages ▪ Used for direct tableting ▪Disadvantages ▪ Very hygroscopic above 65% relative humidity ▪ It may be blinded with mannitol or other excipients to reduce its moisture pick-up.  COMPONENTS ▪ Essential Components ▪ Sucrose ▪ Advantages ▪ Provides additional Sweetness ▪ Serves as binder since it has cohesive properties ▪ Contributes to dissolution of the tablet since it is readily soluble  COMPONENTS ▪ Essential Components ▪ Sucrose ▪Disadvantages ▪ Somewhat hydroscopic so that its ratio in the formula should be small ▪ Tends to turn brown in contact with acidic and basic substances.  COMPONENTS ▪ Essential Components ▪ Microcrystalline Cellulose (avicel) ▪Advantages ▪ Used for direct compression formulation ▪ At 5-15% concentration in wet granulations: a. Minimizes case-hardening of tablets b. Reduces tablet mottling  COMPONENTS ▪ Essential Components ▪ Microcrystalline Cellulose (avicel) ▪Disadvantages ▪ Presence of drug may necessitate addition of lubricant to formulation ▪ Expensive  COMPONENTS ▪ Essential Components ▪ Binders ▪ The choice of binding agents depends on the binding forces required to form granules and its compatibility with other ingredients as revealed by stability studies. ▪ Influence the characteristic of the compressed tablets ▪ Disintegration? ▪ Excessive wear of Punches and disc – d/t heavy pressure ▪ Mottling of tablets  COMPONENTS ▪ Essential Components ▪ Binders ▪ Water and Alcohols? ▪ Lactose and Starch? ▪ Binders used as a solution is more effective than the same amount of binder which is dispersed in dry form and moistened with the solvent. ▪ The binding sol’n. can easily penetrate the film of adsorbed air coating each particles of the powder blend  COMPONENTS ▪ Essential Components ▪ Binders ▪ Recommended Binding Solutions: 1. Starch paste: aq. Sol’n of corn starch 10-2-% w/w 2. Aq. Gelatin Solution: 10-20% w/w 3. Aq. Glucose solution: 25-50% w/w 4. Alcoholic Solution of ethylcellulose 5% w/w  COMPONENTS ▪ Essential Components ▪ Disintegrants ▪ The rate with which the API is released from the tablet matrix is measured by disintegration time of the tablet. ▪ Factors affecting disintegration time: 1. Disintegrants 2. Its selections 3. Its quantity 4. Mode of addition to the formulation  COMPONENTS ▪ Essential Components ▪ Disintegrants ▪ Classification 1. Starches (corn and potato) 2. Clays (Bentonite and Beegum) 3. Cellulose (Methylcellulose, Na CMC, microcrystalline cellulose) 4. Algins (alginic acid and Sodium Alginate)  COMPONENTS ▪ Essential Components ▪ Disintegrants ▪ Classification 5. Gums ( Locust bean, Karaya, Guar, Tragacanth, and Agar) 6. Effervescent mixtures  COMPONENTS ▪ Compressed Aides ▪ Lubricants ▪ Glidants ▪ Anti-adhesive  COMPONENTS ▪ Compressed Aides ▪ Lubricants ▪ Prevent friction and wear ▪ True Lubricant action is particularly required immediately after compression of the tablet within the die to reduce the friction between the inner die walls and tablet edge during the ejection cycle. ▪ Poor Lubrications→? ▪ Help granules Slip and slide  COMPONENTS ▪ Compressed Aides ▪ Glidants ▪ Improve the flow characteristics of granulation by reducing the interparticulate friction. ▪ Eliminating the problem associated with the flow of materials from larger through smaller apertures in the tablet presses ▪ Serve to assure smooth and uniform flow at all times  COMPONENTS ▪ Compressed Aides ▪ Anti-adhesive ▪ To prevent tablet granulation or materials from sticking to the faces of the punches and the die walls  COMPONENTS ▪ Supplementary Components ▪ Colorants ▪ Flavors and Sweeteners ▪ Adsorbents  COMPONENTS ▪ Supplementary Components ▪ Colorants ▪ BFAD or FDA Approved ▪ Approved colorants ▪ FD & C ▪D & C ▪Mottling – increase in Colorant used ▪Pastel colors are preferred  COMPONENTS ▪ Supplementary Components ▪ Colorants ▪ Several Approaches to the addition of colorants to a tablet formulation: 1. Most common method is to incorporate a soluble dye in the binding solution prior to the granulating process. (o.3% max conc.) 2. Adsorbed the dye on starch or Ca sulfate from its aq. Sol’n. the resultant powder is dried and blended with other ingredients 3. It may also blended dry with a portion of the diluent and distributed during the dry mixing operation with the rest of the formulation.  TABLET PRESSES Basic Elements of tablet press 1. Hopper 2. Feed Frame 3. Dies (controlling the size and shape of the tablet) 4. Punches (compacting the material) 5. Cams (guiding the panches ▪ The basic mechanical unit tablet compression involves the preparation of two steel punches within the steel die cavity. ▪ The tablet assumes the shape of the punches and die used. ▪ Weight of the tablet? ▪ Thickness?  Types of Compression Machine 1. Single Punch 2. Multistational rotary presses  Care of Compression Machine ▪ Proper maintenance of punches or die  Care of Compression Machine ▪ Some practical rules in the care and handling of the toolings are: 1. Do not allow the punches to drip on the concrete or similar hard surface which will chip the fine edges 2. Never allow the upper and lower punch faces to come in contact with each other → bend or flatten out the fine sharp edges of the pinches which causes capping of the tablet.  Care of Compression Machine ▪ Some practical rules in the care and handling of the tooling are: 1. After production, toolings are removed from the machine, washed thoroughly in warm soapy water, then dried with a clean towel or cloth. A coating of oil should then be applied to protect from the atmospher. 2. Storage of hard paper tubes in which punches are shipped from the factory, or hanging then in wooden racks after thorough lubrication is recommended  Care of Compression Machine ▪ Tablet machine should received the best possible care to insure maximum operating efficiency. Observe the following rules: 1. Keep the machine clean 2. Keep parts properly lubricated 3. Avoid overloading 4. Insert dies carefully  Tablet Granulations ▪ Granulations – is a pharmaceutical process that attempts to convert powdered materials into aggregates called granules ▪ Properties: 1. Fluidity (hopper into feed frame) 2. Compressibility  Tablet Granulations ▪ Good tablet Granulation should: 1. Contains particles which approach spherical shape. 2. Present a range of particle size that resembles normal distribution curve, with a small percentage of coarse and fine particles and with the rest in the narrow range between. 3. Uniform Distribution of all ingredients in the formulation 4. Possess compressible components that will confer physical strength and form of the tablet.  Methods 1. Dry Methods a. Direct Compression b. Granulation by compression 2. Wet Methods a. Wet Granulations b. Special Procedures/ related granulation process  Dry Methods ▪ Preferred Method ▪ Do not required the equipment and handling expenses required in wetting and drying procedures ▪ May obviate loss of activity with those drugs are moisture- and heat- sensitive.  Direct Compression Presents several drawbacks namely: 1. Its limited few crystalline substance, such as inorganic salts (NaCl, NaBr, KCl) which may be compressed directly; the vast majority of medicinal agents are rarely so easy to tablet. 2. Compression of a single substance may produce tablets that do not disintegrate. 3. Other components, may interfere with the compressibility of the active ingredient thus minimized the usefulness of the method 4. The effective dose of many drugs is so small that direct compression would be impractical and uneconomical.  Granulation by compression ▪ Dry Granulation ▪ Precompression or ▪ Double Compression Method ▪ The methods involves compaction of finely divided powdered materials into large, poorly formed but firm masses called “SLUGS”.  Dry Granulation Methods includes the following Steps: 1. Weighing of the Ingredients 2. Mixing of ingredients in a suitable mixer or blender. 3. Slugging Using flat face punches 7/8 to inch diameter 4. Dry screening of slugs through a mesh screen (by hand) or through fritzpatrick comminuting mill. 5. Lubrication through as suitable blender 6. Compression into final tablets.  Wet Methods ▪ Most widely used and most general method of preparing tablet granulation that will satisfy the physical requirements for the compression of good tablets. ▪ Disadvantages: ▪ It involves separate steps ▪ Required Longer processing time ▪ Labor cost is High  Wet Methods ▪ Steps 1. Weighing of ingredients 2. Mixing them in a suitable mixer or blender 3. Granulation into a damp mass by the addition of binding solutions 4. Screening the mass by forcing through a 6 or 8 mesh screen. 5. Drying in suitable ovens of fluid bed dryers  Wet Methods ▪ Steps 1. Dry Screening through smaller mesh screen 2. Lubrication in a suitable blender 3. Compression into final tablets  Tablet Characteristics 1. Diameter Size 2. Shape 3. Thickness 4. Weight 5. Hardness 6. Disintegration Time 7. Dissolution  Problems 1. Chipping 2. Capping 3. Lamination 4. Mottling 5. Weight Variation 6. Hardness Variation 7. Double Impression – lower punches