Tablet Dosage Forms PDF

DIPLOMA OF PHARMACY PROGRAM PHD212 Solid Dosage Forms: Chapter 3 Tablets PREPARED BY: NURSYUHADA AZZMAN (RPH ) EDITED AND PRESENTED BY: DR. MOHD NADZRI M...

DIPLOMA OF PHARMACY PROGRAM PHD212 Solid Dosage Forms: Chapter 3 Tablets PREPARED BY: NURSYUHADA AZZMAN (RPH ) EDITED AND PRESENTED BY: DR. MOHD NADZRI MOHD NAJIB FACULTY OF PHARMACY, UiTM CAW. PULAU PINANG KAMPUS BERTAM 2 Lesson Outcomes At the end of this lecture, one should be able to: Understand the various types of tablets, advantages, disadvantages and essential qualities of tablets Understand the materials used to prepare the tablets Understand quality standards, containers, labelling and storage of tablets Introduction Definition: Tablets are solid unit dosage form containing one or multiple drug substances with or without suitable excipients in powder or granule form, pressed or compacted into a solid dose usually circular in shape and maybe flat or biconvex Tablet technology made an outstanding progress and is an advance science now It is the most popular dosage form in use today Advantages of Tablet  Unit dose  Simple to identify (each individual unit)  Most stable of all oral preparations  Patient acceptance – convenient  Formulation can be manipulated (XR, SR)  Reproducibility  Manufacturing is well established & cost is low  Less susceptible to tempering (transportation)  Rate and site of dissolution can be control – less SE/Toxic  Easy to carry, storage and dispensing  Incompatible drugs can be manufactured together – like bilayered tablets  Production – can be done in short period of time Disadvantages of Tablet Problems with bioavailability. Cannot be administered to unconscious patient Some drugs resist compression Dose too large – size limit for tablets Not suitable for drugs susceptible to degradation by oxygen or moisture Not suitable for paediatric Onset of action is slow Classification of Tablets Tablets are being classified according to the basis of: Route of administration or function Type of drug delivery system they represent within that route Form and method of manufacture (preparation) - In general, there are two classes following their preparation – molded or compressed Classification of Tablets A. Tablets ingested orally 8324 B. Tablets used in the oral cavity C. Tablets administer by other route D. Tablets used to prepare solution A. Tablets Ingested Orally 1. Compressed Tablet 2. Multiple Compressed Tablets 3. Multilayer Tablet 4. Sustained action Tablet 5. Enteric Coated 6. Sugar Coated 7. Film Coated 8. Chewable Tablets 10 B. Tablets used in the oral cavity 1. Buccal or sublingual 2. Lozenges /troches & pastilles 3. Dental cone 11 C. Tablets Administered by Other Route 1. Implantation Tablet 2. Vaginal Tablet 12 D. Tablets used to prepare Solution 1. Effervescent Tablet 2. Dispersing Tablet 3. Hypodermic Tablet 4. Tablet Triturate 13 TYPES OF TABLETS A. Tablets ingested orally B. Tablets used in the oral cavity C. Tablets administer by other route D. Tablets used to prepare solution 14 Single compressed tablets Prepared by compression. Contains active drug plus adjuvants/excipients (additives, adjuncts). Examples of compressed tablets include tablets for oral, buccal, sublingual, or vaginal administration. Multiple compressed tablets Compressed coated type-either tablet within a tablet or tablet within a tablet within a tablet. The inner tablet being the core and the outer portion being the shell. 16 Multilayer Tablet Layered tablet either two layered (for two components) or three layered (for three components) tablet. more than one compression step is involved. results in a multiple-layered tablet within a tablet (shell and core). each layer is usually colored with a different color. 17 Objective of Preparing Multilayer Tablets To use different APIs in combination. To get dual release profile so as to reduce dosing frequency and thereby increasing patient Compliance. To combine compatible or incompatible drugs with different release characteristic in same dosage form and enhancing the stability of dosage form as compared to its dosage form. 18 Advantages of Compression Large scale production at lowest cost Medicinal agents are separated to prevent incompatibility, or each layer provides drug release at a different stage or for coating purposes. Elimination of water or other solvent in the coating procedure for coated compression tablet Immediate release portion is compressed around a slowly releasing core which provides accurate dose compare to simple matrix table Disadvantages of Compression Tedious and expensive process requires accurate and precise machinery. It has not yet replaced film coating due to simple and inexpensive nature of film coating Compression coated tablets produce significant increase in size and weight of the core tablets compared to film coated tablets. Some drugs resist compression into dense compact Sustained action Tablet Used to get sustained action of medicament. These tablets when taken orally, release the medicament in sufficient quantity as & when required to maintain the maximum effective concentration of the drug in blood throughout the Period of treatment. Prefix used includes, sustained release (SR), extended release (XR) 21  COATING Coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits over uncoated variety. WHY COAT TABLETS? to protect the medicinal agent against destructive exposure to air and/or humidity. to mask the taste of the drug upon swallowing. to provide special characteristics of drug release (e.g. enteric coatings). to provide esthetics or distinction to the product. to prevent inadvertent contact with the drug substance (e.g. Proscar,Merck) tablets Sugar-Coated Film-Coated Tablet Coating Enteric-Coated Micro-encapsulation Enteric Coated Coating resist dissolution or disruption in the stomach but not the intestines 25 Advantages of Enteric Coated: protects drugs that are destroyed in acid medium protects the stomach from drugs that cause irritation to the gastric mucosa. used when by-pass of the stomach greatly enhances drug absorption. Sugar Coated coating is sugar-based, water soluble and quickly dissolves after swallowing. coating may be colorless or colored. appearance may be rounded with high degree polish 27 Advantages of Sugar Coated protects drugs from the effects of air and humidity. masks unpleasant odor and taste. enhances the appearance of compressed tablets. Disadvantages of Sugar Coated time and expertise required for the process. increase in the size and weight of the tablet (50% increase). logo or break-line is not possible multistage process 8 hours but usually longer not possible for functional coating (except enteric) Film Coated It involves application of a water soluble or water-insoluble polymer film to the surface of the compressed tablet that ruptures in the GI tract. Retain shape of original core 30 Types of Film-Coating Used The applications for use of film-coating are quite diverse. While such application require functionality of the coating formulation, it is not uncommon to see film coating described as: either functional or non-functional (conventional) Functionality relates specifically to an ability to modify drug release characteristic Types of Film-Coating Used Non-functional (conventional) film coating are typically reserved for situations in which it is necessary to improve the: Product appearance Ease of swallowing Product stability Mechanical resistance Palatability (to mask the taste) Types of Film-Coating Used Functional film coating are used when drug release characteristics need to be modified, and are represented by: Enteric (gastroresistant) Modified (MR) /Sustained (SR) /Control (CR)/Extended release (XR) Target release coating Advantages of Film Coated Substantial reduction in quantity of coating applied (2-4% for film coated, compared to 50 – 100% for sugar coated) – more durable, less bulky. Less time consuming to apply (1.5-2hours). Usually single stage process/simplified process Easily adaptable for controlled release (SR/XR/ enteric coated) Ability to be applied a wide range of pharmaceutical products Disadvantages of Film-Coated Implication on environment and safety as it use organic solvent Financial expense TYPES OF TABLETS A. Tablets ingested orally B. Tablets used in the oral cavity C. Tablets administer by other route D. Tablets used to prepare solution 36 1. Buccal or sublingual tablets Generally flat, oval tablets intended to dissolve in the buccal pouch or beneath the tongue for absorption through the oral mucosa. Tablets intended for buccal administration are formulated to dissolve slowly (progesterone tablets) whereas those for sublingual administration dissolve very promptly to give rapid drug effects. Advantages: Used for drugs that are destroyed by gastric juice and/or are poorly absorbed from the GI tract Absorbs quickly, rapid onset. These types of administration can be important during emergencies (e.g: heart attack) Increase ease of drug administration. Sustain drug delivery could be achieved. Disadvantages: Dose not as accurate as film, patch or swallowed tablets. Low membrane permeability compare to sublingual. Only for drug with small dose requirement Secretion of saliva leads to subsequent dilution and loss of drug 2. Chewable tablets Have a smooth rapid disintegration when chewed or allowed to dissolve in the mouth. Formulated in mannitol. Used mainly for children’s multivitamin tablets and for the administration of antacids and anti-flatulents. 3. Lozenges / troches and pastilles Meant to exercise local action on throat tissues (moulded / compressed now) or to give local quick relief effect Base is hard candy or sugar and an adhesive such as mucilage or gum. Can be made in tablet machines or in a candy-making machine. 4. Dental Cones Placed in empty socket after tooth extraction-antimicrobial drug TYPES OF TABLETS A. Tablets ingested orally B. Tablets used in the oral cavity C. Tablets administer by other route D. Tablets used to prepare solution 42 Implantation tablets Tablets are placed under the skin or inserted subcutaneously by means of minor surgical operation and are slowly absorbed. These may be made by heavy compression but are normally made by fusion. Mainly used for administration of hormones such as testosterone and deoxycorticosterone etc. 43 Vaginal tablets Tablets are meant to dissolve slowly in the vaginal cavity. This tablet form is used to release steroids, antibacterial agents, antiseptics to treat vaginal infections. Contains excipients such as, lactose or sodium bicarbonate. 44 TYPES OF TABLETS A. Tablets ingested orally B. Tablets used in the oral cavity C. Tablets administer by other route D. Tablets used to prepare solution 45 Effervescent tablets Prepared by compression of granular effervescent salts that release gas when in contact with water. Advantages: Fast disintegration and dissolution of drug for rapid action (alkalinizing analgesic tablets). Provide a mean of extemporaneous preparation with accurate drug dose Produce pleasantly flavored carbonated drink which assists in masking the taste of certain drugs Disadvantages: Difficulty of producing a chemically stable product Sensitive to humidity, easily reactive to moisture in air to give effervescent effect Brittle Tablet Triturates (grind to a fine powder Small, usually cylindrical molded or compressed tablets containing small amounts of usually potent drugs. Diluent is usually sucrose and lactose, water-insoluble materials are avoided in the formulation: tablet triturates must be readily soluble in water. Uses of Tablet Triturate Oral or sublingual administration of drugs (e,g Nitroglycerin). Compounding of other dosage forms. Insert directly one or more of these in a capsule for accurate dosing. To fortify liquid preparations. Hypodermic tablets (discontinued) Tablet triturates originally intended to be dissolved by a physician in a suitable vehicle and parenteral administration after sterility was attained as best as the physician could. Dispensing tablets (Discontinued) no longer in general use. these were used to compound other dosage forms and contained relatively large amounts of potent drugs (this was more convenient to use than weighing the actual amount of ingredient). all ingredients were soluble and these tablets contained no lubricant, disintegrant, color or flavor. potential hazard in inadvertent dispensing as such to patients. MATERIAL REQUIRED Excipients 52 EXCIPIENTS Diluents Granulating/Binding agents Disintegrating agents Flavouring agents/ Colorants Lubricants Antiadherent Glidants  Diluents or Filler: designed to make up the required bulk of a tablet when the drug dosage amount is inadequate. The also improve cohesion. e.g. lactose, microcrystalline cellulose, starch, powdered sucrose and calcium phosphate (avoid calcium salts with tetracycline). Disintegrants: These are added to tablet formulations to facilitate tablet disintegration upon tablet contact with water. They appear to function by drawing water into the tablet, swelling and causing the tablet to burst apart. e.g. cornstarch and potato starch, starch derivatives such as sodium starch glycollate, cellulose derivatives such as sodium carboxymethyl- cellulose, clays such as Veegum and bentonite, etc...  Glidant improve flowability of the tablet granulation by reducing friction between them. Usually glidant is added prior compression. flow from hopper to die Lubricant reduces friction between the tablet and the walls of the die cavity. a very small quantity (usually 0.25%–5.0%, w/w) Antiadherent reduces sticking of the tablet to the die and punch. *The examples for these agents are listed in the next slide 56 57 TABLETS Methods of Preparation Summary of Tableting Process The process of making tablets involving: Wet granulation Dry granulation Direct compression Fluid bed granulation (recent technology). Wet Granulation (you covered this step in depth already) Widely employed method for the production of compressed tablets. Formed by addition of granulation liquid which contain solvent that will be removed during drying process The liquid can be solvent-based or aqueous-based Aqueous-based is safer but need binder (e.g: povidone) Steps of Tableting (Wet Granulation) 1. weighing and blending the ingredients. 2. preparing the wet granulation. 3. screening the damp mass into pellets or granules (dry granulation) 4. drying the granulation 5. dry screening & mixing 6. lubrication and blending. 7. tableting by compression. STEPS IN TABLETTING 1. Weighing and blending: The active ingredient and any filler and disintegration agent ( or part thereof ) are weighed and mixed thoroughly. 2. Preparing the wet granulation: The powder is converted to granules in order to improve flow characteristics. A liquid binder or and adhesive is added to the powder mixture (aqueous preparation of cornstarch, solution of glucosem molasses, natural gums such as acacia, cellulose deruvatives such as methylcellulsoe, CMC, gelatins, and povidone.  of granulation liquid onto a powder bed under the influence of:  an impeller (in a high-shear granulator)  screws (in a twin screw granulator)  or air (in a fluidized bed granulator) Colors and flavors can also be added. If the drug substances is affected by water use a non-aqueous binder (e.g: ethylcellulose). Amount of binder depends on manufacturer’s experience. Overwetting causes granules that are too hard, underwetting results in tablets that are too soft and friable. 3. Screening the damp mass into pellets or granules: Pass the wet mass through a sieve or screen, wet granules are obtained. 4. Drying the granulation: Spread in a single layer over a sheet of paper or a shallow tray and put in oven or dry in a fluidized bed drier. 5. Dry screening: After the granules are dried, pass through a screen of smaller size than the one used for the wet mass. This process is necessary to select granules of uniform size to allow even fill in the die cavity. Note that the smaller the size of the tablet, the smaller the size of the selected granules. 6. Lubrication and blending A dry lubricant, antiadherent and glidant are added to the granules either by dusting over the spread-out granules or by blending with the granules. 7. Tableting by compression. The granule/lubricant mix is fed through a hopper in the die cavity and then compressed between a lower and an upper punch. Reasons for granulation (covered before) 1) To prevent segregation of the constituents of the mix powder by creating bonds between particles 2) As normally, smaller or denser particles will be concentrated at the base 3) Ideal granulation will ensure that correct proportion of the constituents within each granule thus prevent segregation 4) Some powder also are cohesive (due to small size, shape, surface) and do not flow well 5) Some powder are difficult to compact compared to granules ALL IN ONE GRANULATION METHODS Fluid Bed granulator: Mixing and blending, granulation and drying are carried out in the same apparatus. Microwave vacuum processing: Microwave technology is used to dry faster, vacuum also helps evaporation of solvents. Dry Granulation (covered before) Method specially useful for drugs that are affected by moisture or high temperature involved in wet granulation. Involved aggregation of powder particles under high pressure Dry Granulation (covered before) After mixing and blending, the powder is compressed into large pellets or slugs by passing through a double roller or by compression in a “slugging” machine. The slugs are then broken up and screened. e.g. aspirin. Disadvantage of slugging/tablet press Powder sometimes does not posses enough natural flow to fill cavity thus cause varying density Direct compression Some granular chemicals are suitable for direct compression (free flowing) e.g. potassium chloride. Tableting excipients with good flow characteristics and compressibility allow for direct compression of a variety of drugs. TABLETS Coating Process  Sugar-coated tablets Steps: 1. Waterproofing and sealing (e.g. Shellac in alcohol). A seal coat is applied over the tablet to prevent moisture penetration into the tablet core. Shellac was previously used as a sealant. But due to polymerization problems, it was replaced by zein (a corn protein derivative). 2. Subcoating: This step is done to round the edges and increase the tablet weight. Apply layers of heavy syrup with gelatin, Povidone or gum then sprinkled with powdered sugar and starch (talc, acacia, precipitated chalk may also be used). 3. Smoothing and final rounding: roll tablets in heavy syrup (may contain coloring) and dry with warm air. 4. Finishing and coloring: roll tablets in light syrup (may be colored) in a clean pan. The tablet are then imprinted for identification. 5. Polishing: use fabric (canvas) impregnated with carnauba wax with or without beeswax. Or apply wax dissolved in a nonaqueous solvent such as acetone, then add talc. Film-coated Tablets Film-coating places a thin skin-tight coating of a plastic-like material over the compressed tablet. The film may be made of a water soluble or water-insoluble material e.g. hydroxyproplmethylcellulose, ethylcellulose, povidone or PEG. Film-forming solutions contain: A film former. (eg: polymer) An alloying substance (to allow penetration of water or body fluids) e.g. PEG. A plasticizer to produce flexibility and elasticity of the coating (e.g. castor oil) A surfactant to enhance the spreading of the film forming solution on the tablet e.g. spans. Opaqants and colorants e.g. Titanium dioxide and F,D& C or D&C colorants.  Sweeteners, flavors, and aromas: e.g. saccharin, vanillin. A glossant to provide luster e.g. beeswax. A volatile solvent e.g. alcohol-acetone mixture. The volatile solvents are expensive, potentially toxic, possibly explosive, aqueous based film-forming solutions can be used e.g. Aquacoat. These aqueous base formulations contain: 1. Film-forming polymer e.g. HPMC, hydroxypropylcellulose and methylcellulose. 2. Plasticizer e.g. glycerin, PEG 3. Colorant and opacifier F,D&C or D&C lakes. 4. Water as the solvent. Enteric Coated The coat can be applied to the tablet or to individual granules that will then be compressed into a tablet or to be filled into a capsule. Materials used for enteric coating: shellac, cellulose acetate phthalate fats and fatty acids. Coating Methods Fluid-bed or air suspension coating In the Wurster process, the items fed into a into a vertical cylinder and are supported by a column of air. Compression coating Similar to the preparation of multiple compressed tablets, the coating material is compressed around the tablet core.  TABLETS Packaging & Storage  Store in tight containers and in places with low humidity or extreme temperature. If drug is adversely affected by light, pack in a light-resistant container. Products sensitive to moisture may be packaged with a desiccant.  Proper storage conditions should be followed by the pharmacist and the patient and expiration dates observed. Cotton and rayon may absorb drug, making the product sub-potent e.g. nitroglycerin FDA Regulation in 1972: 1. All nitroglycerin tablets must be packaged in glass containers with tightly fitting metal screw caps. 2. No more than a 100 tablets in each container. 3. Must be dispensed in their original container, bearing label: “Warning: To prevent loss of potency, keep these tablets in the original container. Close tightly immediately after use. 4. All nitrogylcerin tablets should be stored at controlled room temperatures of between 590 and 860F. Note: Nitrostat contains PEG as a stabilizer to prevent evaporation of nitroglycerin.  TABLETS Processing Problems 1. Capping: partial or complete separation of the top or bottom crown. Can be the result of dirty or worn out punches. lamination is the separation of a tablet into two or more layers. both of these problems result from air entrapment during processing. ( add fines to overcome the problem). 2. Picking & Sticking (Chipping) Removal of a tablet’s surface material by a punch. Sticking & picking is a adhesion of the tablet material to the die wall. due to excessive moisture, low melting point substances in the or not enough lubricant. 3. Mottling: Unequal distribution of color, with light or dark spots. Can be due to drug and excipient of different colors, formation of degradation products.  4. Weight variation Multifactorial however most of it occurs due to a lack of freely flowing powder/granules 5. Hardness variation Multifactorial reason and also related to granulation process 6. Double impression Due to free rotation from the puncher COMPRESSED TABLET Characteristic & Quality Characteristics & Quality Various shapes: round, oblong, triangular, square, rectangular, etc... Thick or thin, flat or convex, might be scored (grooved) for administration of partial amounts. Carry a symbol used for identification, may be colored for further distinction. Tablet diameter and shape is determined by the die and punch. Tablet thickness is determined by the amount of compression pressure. Other characteristics that pharmacists are aware of but might be unknown to the layman: tablet weight, tablet hardness, tablet disintegration, content uniformity and drug dissolution. TABLETS Quality Control Quality Control (QC) of Tablet 1. Tablet weight: Determined by the amount of fill placed in the die ( is measured by volume and not by weight and therefore depends on the granule size and the void space). 2. Weight variation: USP contains a weight variation standard to which the official tablets must conform. 3. Tablet hardness or breaking strength: 3,000 to 40,000 lbs of force can be applied during compression in tablet manufacture, the greater the pressure applied the harder the tablet. Tablets that are intended to dissolve slowly such as lozenges or buccal tablets are intentionally made hard, whereas tablets intented to dissolve fast such as tablet triturates are intentionally made soft. 3. Tablet hardness or breaking strength: Generally tablets are made so that they are hard enough to resist breakage during packaging, shipping and handling yet soft enough to disintegrate and dissolve properly after administration. Hardness measuring devices apply increasing pressure on the tablet until the tablet breaks (a force of about 4 kilograms is considered to be a minimum for hardness). Hardness Test Machine 4. Friability testing The use of a friabilator that determines the tablet’s friability (1% weight loss is the maximum acceptable weight loss). 5. Tablet disintegration: Tablet disintegration results in an increase in surface area to provide more surface for dissolution or release of the drug so that the drug can exert its effect. All USP tablets must pass the official test for disintegration (about 30 minutes disintegration time but might vary). 6. Tablet dissolution: Dissolution characteristics are an important characteristic of a satisfactory drug product. USP contains a test that determines the dissolution characteristics.  Essential Qualities of Good Tablet 1) Must have good strength to stand tear and wear during packing and transportation 2) Must disintegrate and dissolve the drug at the predetermined period of time 3) Must maintain the shape of the tablet through out its shelf life 4) Must posses long expiry date 5) Should hard enough to withstand all mechanical shocks during coating of the tablet 6) Should release the drug at as per programmed for release of drug like delayed, constant release type