04_Manufacture_of_Tablets_Part_1-1.pdf

Manufacture Solid Dosage Forms Tablets Part 1 Leigh Don T. Villanueva, RPh Pharmacy 305: Manufacturing Pharmacy  Tablets Solid pharmaceutical dosage forms containing drug substances with or without suitable diluents and have been traditional...

Manufacture Solid Dosage Forms Tablets Part 1 Leigh Don T. Villanueva, RPh Pharmacy 305: Manufacturing Pharmacy  Tablets Solid pharmaceutical dosage forms containing drug substances with or without suitable diluents and have been traditionally prepared by either compression, or molding methods. Pharmacy 305: Manufacturing Pharmacy  Tablets Compressed tablets Believed to have been used first by John Wyeth and Brother of Philadelphia. Molded tablets introduced to be used as hypodermic tablets for the extemporaneous preparation of solutions for injection. Pharmacy 305: Manufacturing Pharmacy  Advantages MANUFACTURER Simplicity and economy of preparation Stable Convenience in packaging, shipping and dispensing Pharmacy 305: Manufacturing Pharmacy  Advantages PATIENTS Accuracy of dosage Compactness Portability Blandness of taste Ease of administration Pharmacy 305: Manufacturing Pharmacy  Types of Tablet COMPRESSED TABLETS COMPRESSED TABLETS (CT) Tablets are formed by compression and in the simplest form, contain no special coating. Made up of: Powdered, crystalline, or granular materials alone or in combination with binders, disintegrants, controlled-release polymers, lubricants, diluents, and n many cases colorants. Pharmacy 305: Manufacturing Pharmacy Types of Tablet Compressed, Coated Tablet  Coating Principle application of coating material to a moving bed of solids with concurrent use of heated air to facilitate evaporation of solvent Pharmacy 305: Manufacturing Pharmacy  Reasons for Coating I. Therapy A. Improve patient compliance i) Avoid irritation of esophagus and stomach ii) Avoid bad taste B. Improve drug effectiveness i. Avoid inactivation of drug in the stomach ii. Prolong or improve dosing interval II. Technology A.Improve drug stability i. Reduce influence of moisture/atmosphere ii. Prolong shelf life B. Avoid dust formation Pharmacy 305: Manufacturing Pharmacy  Reasons for Coating III. Marketing A.Avoid bad taste B. Improve product identity C.Improve appearance and acceptability Pharmacy 305: Manufacturing Pharmacy  Requirements of Tablets to be coated 1. optimum convexity 2. sufficient hardness 3. minimal friability 4. rapid disintegration 5. dust-free Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Compressed, Coated Tablet Sugar-Coated Tablet (SCT) Compressed tablets surrounded by sugar coating. Such coating may be colored and are beneficial in covering up drug substances possessing objectionable tastes or odors and in protecting materials sensitive to oxidation. Pharmacy 305: Manufacturing Pharmacy  Sugarcoating coating is water soluble and quickly dissolves after swallowing enhances the appearance of the compressed tablet and permit imprinting manufacturing’s information provides a combination of insulation, taste masking, smoothing the tablet core, coloring and modified release. Disadvantages: time and expertise requirement increased size, weight and shipping costs Pharmacy 305: Manufacturing Pharmacy  Steps in Sugarcoating 1. Sealing/Water proofing provides a moisture barrier and harden the tablet surface. 2. Subcoating causes a rapid buildup to round off the tablet edges. 3. Grossing/Smoothing smoothes out the subcoated surface and increases the tablet size to predetermine dimension. 4. Coloring gives the tablet its color and finished size. 5. Polishing produces the characteristics gloss. Pharmacy 305: Manufacturing Pharmacy  Materials Used in Sugarcoating 1. Sealing/Water proofing Shellac, Zine, Cellulose acetate phthalate (CAP), Polyvinylacetate phthalate, Hyroxylpropylcellulose, Hyroxypropylmethylcellulose 2. Subcoating gum-based solution 3. Grossing/Smoothing syrup solution (60-70 % sugar) generally contains pigments, starch, gelatin, acacia or opacifier Pharmacy 305: Manufacturing Pharmacy  Materials Used in Sugarcoating 4. Coloring syrup solution (60-70 % sugar) containing colorant soluble dyes predispersed opacified lake suspension 5. Polishing beeswax, carnuba wax, candelila wax or hard paraffin wax Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Film-Coated Tablets (FCT) These are compressed tablets that are covered with a thin layer or film of a water-soluble material. Imparts the same general characteristics as sugar coating, with the added advantage of a greatly reduced time period required for the coating operation. Pharmacy 305: Manufacturing Pharmacy  Film Coating Polymer is solubilized into solvent with plasticizers and pigments tablet core. Usually spray process is employed Accela cota: perforated cylindrical drum providing high drying air capacity Fluidized bed equipment: tablets are moving in a stream of air passing through the perforated bottom of a cylindrical column; requires very hard tablets (hardness > 20 N) Pharmacy 305: Manufacturing Pharmacy  Materials used in film coating Film formers, which may be enteric or nonenteric HPMC, Povidone, Na CMC, PEG, Acrylate Polymers Solvents water, ethanol, methanol, isopropanol, chloroform, acetone, methylene chloride Plasticizers castor oil, PG, glycerin, lower molecular weight (200-400 series), PEG, surfactants Pharmacy 305: Manufacturing Pharmacy  Materials used in film coating Colourants Opasray (opaque color concentrate) and Opadry (complete film coating concentrate) Opaquant-Extenders titanium dioxide, silicates, carbonates, oxides and hydroxides Miscellaneous coating solution components Flavors, sweeteners, surfactants, antioxidants, antimicrobials Pharmacy 305: Manufacturing Pharmacy  Film Coating VS Sugar Coating Features Sugar Coating Film Coating Appearance Rounded with high degree of Not as shiny as sugar coat polish and retains contour Weight increase 30-50% 2-3% Logo or “break” lines Not possible possible Other solid dosage forms Coating possible but little Very important in modified importance release forms Stages Multistage process Usually single stage Batch coating time Eight hours or longer 1.5-2 hours Functional coatings Not usually possible apart Easily adaptable for from enteric coating controlled release. Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Enteric-Coated Tablets (ECT) Compressed tablets coated with substances that resist solution in gastric fluid but disintegrate in the intestine. Enteric coatings can be used for tablets containing drug substances that are inactivated or destroyed in the stomach, for those that irritate the mucosa, or as a means of delayed release of the medication. Pharmacy 305: Manufacturing Pharmacy  Problems in Coating Blistering detachment of film from the substrate Due to entrapment of gases in or underneath the film due to overheating during spraying or at the end of the coating run Chipping film becomes chipped and dented, usually at the edges Due to a decrease in fluidizing air or speed of rotation of drum Cratering coating whereby volcanic-like craters appears exposing the surface Due to the coating solution penetrates the surface of the tablet, often at the crown where the surface is more porous, causing localized disintegration of the core and disruption of the coating Pharmacy 305: Manufacturing Pharmacy  Problems in Coating Picking isolated areas of film are pulled away from the surface when the tablet sticks together and then part. Due to conditions similar to cratering producing an overly wet tablet bed where adjacent tablets can stick together and then break apart Pitting pits occur in the surface of a tablet core without any visible disruption of the film coating. Due to a temperature of the tablet core greater than the melting point of the materials used in the tablet formulation Blooming coating becomes dull immediately or after prolonged storage at high temperatures. due to collection on the surface of low molecular weight ingredients (usually plasticizers) included in the coating formulation Pharmacy 305: Manufacturing Pharmacy  Problems in Coating Blushing whitish specks or haziness in the film. due to precipitated polymer exacerbated by the use of high coating temperature at or above the thermal gelation temperature of the polymers. Colour variation uneven color of the film. Due to alteration of the frequency and duration of appearance of tablets in the spray zone or the size/shape of the spray zone Pharmacy 305: Manufacturing Pharmacy  Problems in Coating Infilling Indistinct intagliations Due to inability of foam (formed by air spraying of a polymer solution) to break; foam droplets on the surface breakdown readily due to attrition but the intagliations form a protected area allowing the foam to accumulate and “set” Orange peel/Roughness film is rough and nonglossy Due to nadequate spreading of the coating solution before drying Pharmacy 305: Manufacturing Pharmacy  Problems in Coating Cracking/Splitting cracks across the crown of the tablet (cracking) or splits around the edges of the tablet (Splitting) Due to internal stress in the film exceeds tensile strength of the film Pharmacy 305: Manufacturing Pharmacy  Summary Defect Description Cause Remedy Blistering The film becomes Caused by trapped Reduce inlet air locally detached gas underneath the temperature from the substrate film due to Cessation of the use forming a blister overheating of hot air to dry tablet Chipping Chipped and dented High degree of Increase film hardness at the edges of the attrition associated by increasing the MW tablet with the coating grade of the polymer process Cratering Volcano-like crater Inefficient drying or Increase the drying appearance rate of coating air temperature and solution application is decrease application too high rate Picking Some areas of film Same as cratering Same as cratering pull away from the surface Pharmacy 305: Manufacturing Pharmacy  Defect Definition Cause Remedy Blooming Dulling of the coating Due to the collection Not using hot air to on the surface of low dry the tablets at the molecular weight end of the coating ingredients included run, the decrease in in the coating plasticizer. formulation Blushing Whitish specks or Precipitation of some Decrease the drying haziness in the film polymers by the use air temperature of high coating temp. above the thermal gelation temp of the polymers Infilling Same effect as Inability of a foam, addition of alcohol bridging, logo or formed by air and usage of finer monogram is filled spraying of a polymer spray nozzles with solidified foam solution, to break. structure Mottling Uneven distribution of Mixing problem or Allow more spraying tablet color spray zone problem time to distribute evenly Pharmacy 305: Manufacturing Pharmacy  Defect Definition Cause remedy Orange peel Rough and non glossy Rapid drying Control evaporation tablet rate of the solvent system Bridging Occurs when film Modify tablet surface shrinks during drying to increase porosity process Pharmacy 305: Manufacturing Pharmacy Pharmacy 305: Manufacturing Pharmacy Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Multiple Compressed Tablets compressed tablets made by more than one compression cycle. this process is best used when separation of active ingredients is needed for stability purposes, or if the mixing process is inadequate to guarantee uniform distribution of two or more active ingredients. Pharmacy 305: Manufacturing Pharmacy  MCT Layered Tablets Prepared by compressing additional tablet granulation on a previously compressed granulation. The operation may be repeated to produce multi-layered tablets of two or three, or more layers. Special tablet presses are required to make layer tablets such as the Versa press (Stokes/Pennwalt). Pharmacy 305: Manufacturing Pharmacy  MCT Press-Coated Tablets Also referred to as dry-coated, are prepared by feeding previously compressed tablets into a special tableting machine and compressing another granulation layer around the preformed tablets. They have all the advantages of compressed tablets (ie, slotting, monogramming, speed of disintegration) while retaining the attributes of SCT in masking the taste of the drug substance in the core tablets. Eg. Manesty drycota Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Controlled-Release Tablets (CRT) Formulated to release the drug slowly over a prolonged period of time. Hence, these dosage forms have been referred to as a prolonged-release or sustained-release dosage forms as well. Three types: Those that respond to some physiological condition to release the drug (ECT) Those that release the drug in a relatively steady, controlled manner Those that combine combinations of mechanisms to release pulses of drug (repeat-action tablets) Pharmacy 305: Manufacturing Pharmacy  CRT Other names: Extended Release Sustained Release Prolonged Release Delayed Release In the case of pulsatile tablets: Repeat Action Pulsatile Release Pulse Release Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Tablets for Solution (CTS) Compressed tablets to be used for preparing solutions or imparting given characteristics to solutions must be labelled to indicate that they are not to be swallowed. Eg: Halazone Tablets for Solution; and Potassium Permanganate Tablets for Solution. Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Effervescent Tablets Contain sodium bicarbonate and an organic acid such as tartaric or citric, in addition to the drug substance. In the presence of water, these additives react, liberating carbon dioxide that acts as a disintegrator and produces effervescence. Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Compressed Suppositories or Inserts Occasionally, vaginal suppositories, are prepared by compression. Tablets for this use usually contain lactose as the diluent. In this case, as well as for any tablet intended for administration other than by swallowing, the label must indicate the manner in which it is to be used. Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Buccal and Sublingual Tablets These are small, flat, oval tablets. Buccal (the space between the lip and gum in the mouth) administration inserted into the buccal pouch which may dissolve or erode slowly; therefore, they are formulated as compressed with sufficient pressure to give a hard tablet. Sublingual tablets (eg. Nitroglycerin, isoproterenol HCl, or erythrityl tetranitrate) Placed under the tongue which dissolve rapidly and the drug substance are absorbed readily. Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Molded Tablets or Tablet Triturates TT are usually made from moist material, using a triturate mold that gives them the shape of cut sections of a cylinder. Must be completely and rapidly soluble Problem: failure to find a lubricant that is completely water- soluble. Pharmacy 305: Manufacturing Pharmacy  Types of Molded Tablet Dispensing Tablets (DT) provide a convenient quantity of potent drug that can be incorporated readily into powders and liquids, thus circumventing the necessity to weigh small quantities. Supplied primarily as a convenience for extemporaneous compounding and should never be dispensed as a dosage form Pharmacy 305: Manufacturing Pharmacy  Types of Molded Tablet Hypodermic Tablets (HT) Are soft, readily soluble tablets and originally were used for the preparation of solutions to be injected. Since stable parenteral solutions are now available for most drug substances, there is no justification for the use of hypodermic tablets for injection. Disadvantage: Not sterile No HT ever have been recognized by the official compendia. Pharmacy 305: Manufacturing Pharmacy Manufacture of Tablets  Quality Attributes of Tablets Pharmaceutically Biocompatible Correct Dose elegant ingredients Controlled & Acceptable by reproducible patient release of API Sufficient Stable mechanical strength Pharmacy 305: Manufacturing Pharmacy  Methods of Tablet Manufacture Wet Granulation Dry Granulation Direct Compression 1. Milling 1. Milling 1. Milling 2. Mixing 2. Mixing 2. Mixing 3. Preparation of binder 3. Slugging 3. Compression 4. Mixing with binder 4. Screening 5. Coarse screening 5. Mixing with disintegrant and lubricant 6. Drying 6. Compression 7. Screening 8. Mixing with disintegrant and lubricant 9. Compression Pharmacy 305: Manufacturing Pharmacy  Tablet Granulations Pharmaceutical process that converts a mixture of powders, which have poor cohesion, into aggregates capable of compaction Pharmacy 305: Manufacturing Pharmacy Pharmacy 305: Manufacturing Pharmacy Pharmacy 305: Manufacturing Pharmacy  Manufacture of Granules 1. Direct compression 2. Dry granulation 3. Wet granulation Pharmacy 305: Manufacturing Pharmacy  Direct Compression binding the powders together by compaction 2 operations: powder mixing and tabletting Pharmacy 305: Manufacturing Pharmacy  Direct Compression used for: examples of compressible 1) soluble drugs - processed diluents: as coarse particles § spray dried lactose, Sta-Rx 1500, 2) potent drugs present in a Emdex, Celutab, Avicel few milligrams & can be mixed with coarse excipient particles Examples of APIs § NaCl, NaBr, KCl Pharmacy 305: Manufacturing Pharmacy  Dry Granulation Involves the compaction of the components of a tablet formulation into slugs followed by milling (to produce granular material) & screening (to separate the desired fraction), prior to final compression into a tablet Pharmacy 305: Manufacturing Pharmacy  Dry Granulation used for: Examples 1) drugs that do not § vitamins, aspirin compress well after wet granulation 2) moisture & heat sensitive drugs Pharmacy 305: Manufacturing Pharmacy  Wet Granulation involves the wet massing of the powders, wet sizing or milling, & drying. Pharmacy 305: Manufacturing Pharmacy  Fluid-bed Granulation Granules possess greater porosity and the granule surface is covered by a film of binding agent Pharmacy 305: Manufacturing Pharmacy  Spray Drying method of producing a dry powder from a liquid or slurry by rapidly drying with a hot gas Pharmacy 305: Manufacturing Pharmacy  Process Variables in Granulation Particle Size & Shape Surface Area Density Strength & Friability Flow Properties Compaction Pharmacy 305: Manufacturing Pharmacy  Wet Granulation granules are formed by binding the powders together with an adhesive → solution, suspension, or slurry containing a binder, which is usually added to the powder mixture end-point of massing process can often be determined by inspection 100-800 um Pharmacy 305: Manufacturing Pharmacy  Wet Granulation the binder may be incorporated dry into the powder mix, & the liquid may be added by itself length of time depends on the wetting properties of the powder mixture and the granulating fluid & efficiency of the mixer Pharmacy 305: Manufacturing Pharmacy  Wet Granulation tablets may be made in the traditional manner conventional wet granulation process is labor intensive & time consuming → considerable time is needed to distribute the binder properly throughout the mass high material losses that can be incurred because of the transfer stages Pharmacy 305: Manufacturing Pharmacy  Wet Granulation Wet Dry screening Weighing Mixing Granulation Drying screening Combining Addition of Dry screening IPQC tests Tumbling Compression goods & fines lubricant IPQC tests Bulk Product FPQC tests Packaging Pharmacy 305: Manufacturing Pharmacy  Paracetamol Tablet (example) Paracetamol – Kollidon CL – Dicalcium Phosphate – Kollidon 90F – Ethanol – Magnesium stearate - Pharmacy 305: Manufacturing Pharmacy  Tabletting Machine Type Output Primary Use Single – 200 tablets per minute production of small batches punch aka of tablets during formulation eccentric development press during small-scale production such as production for clinical trials Rotary press 10,000 tablets per during scale-up in the latter aka minute part of the formulation work multistation during large-scale production press Pharmacy 305: Manufacturing Pharmacy  Types of Tablet Presses Single Station Multi-station / Rotary Stokes F Betapress 5,700 tab/hr 16-23 stations Manesty F3 36,000-120,000 tab/hr 5,100 tab/hr Double B Kilian KS 27-45 stations 4,800 tab/hr 45,000-200,000+ tab/hr Pharmacy 305: Manufacturing Pharmacy  Components of a Tablet Press 1. Hopper 2. Dies 3. Punches 4. Cam Tracks 5. Feed Shoe 6. Upper & lower turrets 7. Die table Pharmacy 305: Manufacturing Pharmacy  Single Station Tablet Press Pharmacy 305: Manufacturing Pharmacy  Single Punch Tablet Press Compression is applied by the upper punch, making the single punch machine a “stamping press Pharmacy 305: Manufacturing Pharmacy  Hopper for storing materials for compressing Pharmacy 305: Manufacturing Pharmacy  Feed Frame for distributing the materials into the die feed shoe Pharmacy 305: Manufacturing Pharmacy  Punches for compacting the materials within the die for shaping the tablet Upper Punch and Lower Punch Parts of the punch Pharmacy 305: Manufacturing Pharmacy  Punches may be scored &/or engraved with company names or symbols, trade names, dosage strength, National Drug Code numbers Pharmacy 305: Manufacturing Pharmacy  Punches become worn and the cyclic application of stress can cause the steel to fatigue & break punch tips are especially delicate and susceptible to damage if the tips make contact with each other, the dies or the press turret upon insertion or removal of the tools from the tablet machine Pharmacy 305: Manufacturing Pharmacy  Die for controlling the size and shape of the tablet Pharmacy 305: Manufacturing Pharmacy  Cam Tracks for guiding the movement of the punches Pharmacy 305: Manufacturing Pharmacy Pharmacy 305: Manufacturing Pharmacy  Sequence of Events in Tablet Compression: Single Punch and Rotary Press Pharmacy 305: Manufacturing Pharmacy  Multi-station Rotary Press termed rotary because the head of the tablet machine that holds the upper punches, dies, and lower punches in place rotates as the head rotates, the punches are guided up & down by fixed cam tracks Pharmacy 305: Manufacturing Pharmacy  Multi-station Rotary Press Pharmacy 305: Manufacturing Pharmacy  Sequence of Events in Tablet Compression Pharmacy 305: Manufacturing Pharmacy  Auxiliary Equipment Granulation Feeding Device force granules into die cavity Tablet weight monitoring devices monitors force at each compression station Thomas Tablet Sentinel, Pharmakontroll and Killan control System-MC Tablet Deduster Remove excess powder Fette machine chills the compression components to allow the compression of low melting point substance such as waxes Pharmacy 305: Manufacturing Pharmacy  Attributes of a Well-made Compressed Tablet 1. ability to withstand the rigors of production, packaging, shipment, and dispensing 2. freedom from defects such as cracks, chipped edges, discoloration, speckling, and contamination 3. reasonable chemical and physical stability during average storage conditions 4. ability to release the medicament in a reproducible and predicted manner Pharmacy 305: Manufacturing Pharmacy  Unit Operations Particle Size Mixing Granulation Drying Reduction Compression Coating Printing Packaging Pharmacy 305: Manufacturing Pharmacy  Dry Screening to break up agglomerates of the API & excipients to achieve drug and excipients of the same narrow particle size range Pharmacy 305: Manufacturing Pharmacy  Dry Screening should be done first before weighing the actual raw materials because there is loss of materials upon screening weigh an excess amount of the API & excipients prior to screening Pharmacy 305: Manufacturing Pharmacy  Tools for Dry Screening #40 sieve, Wooden working table, Plastic, Masking tape, 50- or 100-mL Erlenmeyer flask Pharmacy 305: Manufacturing Pharmacy  Weighing to accurately get the mass of the API & excipients add an excess amount of the API & excipients (10% each) to compensate for the loss of material Pharmacy 305: Manufacturing Pharmacy  Tools for Weighing Top loading balance, Pan, Scoops, Containers Pharmacy 305: Manufacturing Pharmacy  Mixing to incorporate the required amount of solvent to form aggregates of powder which in turn can be converted to granules use the minimum quantity of granulating fluid and ensure that it is well distributed → to minimize solute migration Pharmacy 305: Manufacturing Pharmacy  Materials for Mixing Sigma Blade Mixer Pharmacy 305: Manufacturing Pharmacy  Mixing granulating liquid forms bridges between particles & the tensile strength of these bonds increases as the amount of liquid added is increased the mass of powder should be merely moist rather than wet or pasty → there is a limit to the amount of solvent that may be employed Pharmacy 305: Manufacturing Pharmacy  Mixing endpoint of mixing → press a portion of the mass in the palm of the hand → if the ball crumbles under moderate pressure, the mixture is ready for the next stage in processing, the wet screening if excess liquid is added, strings of material will be formed and if the mix is too dry the mass will be sieved to powder and granules will not be formed Pharmacy 305: Manufacturing Pharmacy  Wet Screening involves converting the moist mass into coarse, granular aggregates by passage through a hammer mill or oscillating granulator, equipped with screens having large perforations overly wet material dries slowly and forms hard aggregates, which tend to turn to powder during subsequent dry milling Pharmacy 305: Manufacturing Pharmacy  Tool for Wet Screening hammer mill or oscillating granulator no. 4 hand screen Pharmacy 305: Manufacturing Pharmacy  Drying to reduce the moisture content to an optimum level of concentration within the granules the dry granules should be remixed before compression → ensures that a random mix of enriched & depleted granules will be fed to the tablet machines → to minimize solute migration Pharmacy 305: Manufacturing Pharmacy  Drying to reduce the moisture content to an optimum level of concentration within the granules the dry granules should be remixed before compression → ensures that a random mix of enriched & depleted granules will be fed to the tablet machines → to minimize solute migration Pharmacy 305: Manufacturing Pharmacy  Drying dissolved material can migrate to the upper surface of the bed of granules, as the solvent is only removed from the upper surface of the bed on the tray granules may aggregate owing to bridge formation at the points of contact of the granules Pharmacy 305: Manufacturing Pharmacy  Drying fluid-bed drier → keeps the individual granules separated during drying → reduces the problems of aggregation & intergranular solute migration → reduces the need for sieving stage after drying Pharmacy 305: Manufacturing Pharmacy  Tools for Drying oven (60 °C), trays, porcelain spatula, moisture balance Pharmacy 305: Manufacturing Pharmacy  Dry Screening breaks agglomerates of granules & removes the fine material, which can then be recycled to deaggregate the granules and remix them after drying Pharmacy 305: Manufacturing Pharmacy  Tool for Dry Screening Mesh 20 Screen Pharmacy 305: Manufacturing Pharmacy  Re-granulation to re-granulate and re-screen the portion that passed through mesh 40 screens Pharmacy 305: Manufacturing Pharmacy  Combine Goods & Fines fines comprise 10% of total weight of good granules good granules = the ones that pass through sieve 20 and are retained on sieve 40 fines = the ones that pass through sieve 40 Pharmacy 305: Manufacturing Pharmacy  Drying removal of a liquid from a solid by evaporation Pharmacy 305: Manufacturing Pharmacy  Drying Tray and truck Horizontal vibrating conveyor Fluid bed dryer Spray dryer Flash dryer Microwave dryer Pharmacy 305: Manufacturing Pharmacy  Compression used to make tablets by compressing a formulation containing a drug or drugs with excipients Pharmacy 305: Manufacturing Pharmacy  Compression Single Tablet Press Rotary Press Pharmacy 305: Manufacturing Pharmacy  Tumbling to tumble the solid mixture using a plastic bag Pharmacy 305: Manufacturing Pharmacy  Coating uniform deposition of a layer of material on or around a solid dosage form Pharmacy 305: Manufacturing Pharmacy  Processes of Applying Coats 1. pan coating 2. dip coating 3. compression coating anhydrous operation wherein the powder or granular coating material is compressed onto a tablet core of drug with a special tablet press 4. air suspension coating top spray bottom spray / Wurster tangential spray Pharmacy 305: Manufacturing Pharmacy  Pan Coating Oldest form of pharmaceutical coating for manufacturing small, coated particles or tablets. Pan coating is generally preferred to coat large tablets since they are exposed to mechanical damage in other coating operations. In this process, the particles or tablets are tumbled in a pan which is rotated at an angle of usually 45 degrees Celsius. Pharmacy 305: Manufacturing Pharmacy  Spray System Airless (Hydraulic) Spray Air Spray The coating liquid is pumped under pressure Liquid is pumped, under little or no pressure, to a spray nozzle with a small orifice and to the nozzle and is subsequently atomized atomization of the liquid occurs as it expands by means of a blast of compressed air that rapidly on emerging from the nozzle. makes contact with the stream of liquid as it passes through the nozzle aperture. Pharmacy 305: Manufacturing Pharmacy  Air Suspension Coating is accomplished by suspending solid particles of core material in an upward-moving stream of air, which may be heated or cooled. Pharmacy 305: Manufacturing Pharmacy  Dip Coating The substrate is dipped into a bath of the coating, which is normally of a low viscosity to enable the coating to run back into the bath as the substrate emerges. This process is frequently used on porous substrates. Pharmacy 305: Manufacturing Pharmacy  Printing marking of a capsule or tablet surface for the purpose of product identification Pharmacy 305: Manufacturing Pharmacy  Printing ink-based printing laser printing Pharmacy 305: Manufacturing Pharmacy  Packaging to protect the tablet from extreme conditions (moist & dry) to facilitate the shipping and distribution of the medicine until it reaches the patient Pharmacy 305: Manufacturing Pharmacy  Packaging blister, foil, glass & plastic containers Pharmacy 305: Manufacturing Pharmacy  Thank you for listening