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King Khalid University

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tablet coating pharmaceutical technology drug delivery pharmaceutics

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This document details different types of tablet coatings, including film coatings, sugar coatings, and compression coatings. It explains the reasons for coating tablets, various coating processes, and the components used in film coating formulations such as polymers, plasticizers, colourants, and solvents. The document also briefly describes the sugar coating process.

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Tablets (Part II) Outlines; Tablet coating  Film coating  Sugar coating  Compression coating Types of film coatings Quality Standards And Compendial Requirements Tablets Defects Types of tablets !‫دعواتكم...

Tablets (Part II) Outlines; Tablet coating  Film coating  Sugar coating  Compression coating Types of film coatings Quality Standards And Compendial Requirements Tablets Defects Types of tablets !‫دعواتكم لرانيا‬ Kholod Tablet coating Definition of 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 that broadly range from facilitating product identification to modifying drug release from the dosage form Reasons for coating  Providing a means of protecting the drug substance (active pharmaceutical ingredient) from the environment, particularly light and moisture, and thus potentially improving product stability.  Masking the taste of drug substances that may be bitter or otherwise unpleasant.  Improving the ease of swallowing large dosage forms, especially tablets. Reasons for coating  Providing a means of improving product appearance and aiding in brand identification  Facilitating the rapid identification of a product by the manufacturer, the dispensing pharmacist and the patient.  The coating often improves product flow, increases the mechanical strength of the product and reduces the risk of cross-contamination by minimizing ‘dusting’ problems.  Imparting modified-release characteristics that allow the drug to be delivered in a more effective manner. Types of coating processes  Three main types of process are used in the pharmaceutical industry today: 1) Film coating 2) Sugar coating 3) Compression coating 1) Film coating  Film coating is the most popular technique, and virtually all new coated products introduced to the market are film coated.  Film coating involves the deposition, usually by the spraying of a liquid coating system, of a thin film of a polymer-based formulation onto the surface of a tablet, capsule or multiparticulate core. Types of film coatings  Film coatings may be classified in a number of ways but it is common practice to do so in terms of the intended effect of the applied coating on drug release characteristics. 1. Immediate-release film coatings, also known as ‘nonfunctional’ coatings.  The coating has no measurable effect on biopharmaceutical properties; Examples  Cellulose derivatives; Hydroxypropyl methylcellulose  Vinyl derivatives; poly(vinyl alcohol) (PVA) 2. Modified-release film coatings, also known as ‘functional’ coatings.  These may be further categorized as either delayed-release (e.g. gastro-resistant) or extended-release coatings.  The newer term ‘gastro-resistant’ coating is replacing the older term ‘enteric’ coating in pharmacopoeias. Examples  Cellulose derivatives; ethylcellulose (EC); cellulosic polymers used for modified- release purposes are typically substituted ethers of cellulose  Methacrylic acid copolymers  Phthalate esters polymers; hydroxypropyl methylcellulose phthalate (HPMCP)  Immediate-release coatings are usually readily soluble in water.  Modified-release film coatings  while gastro-resistant coatings are only soluble in water at pH values in excess of 5–6 and are intended to either protect the drug while the dosage form is in the stomach (in the case of acid- labile drugs) or prevent release of the drug in the stomach (in the case of drugs that are gastric irritants).  They are designed to ensure that the drug is released in a consistent manner over a relatively long period of time (typically 6 h to 12 h) and thus reduce the number of doses that a patient needs to take in each 24-hour period. Description of the film-coating process The coating liquid (solution or suspension) contains a polymer in a suitable liquid medium, together with other ingredients This solution is sprayed onto a rotating, or fluidized, mass of tablets. The drying conditions employed in the process result in the removal of the solvent, leaving a thin deposit of coating material around each tablet core. Process equipment The vast majority of film-coated tablets are produced by a process which involves the atomization (spraying) of the coating solution or suspension onto the surface of tablets. Process equipment Modern pan-coating equipment is of the side- vented type Manufacturers of units that operate on a fluidized-bed principle Film-coating formulations  Film-coating formulations typically comprise: A. Polymer B. Plasticizer C. Colourants D. Solvent/vehicle A. Polymer;  Polymer solubility is important for two reasons:  It determines the behaviour of the coated product in the gastrointestinal tract.  It determines the solubility of the coating in a chosen solvent system  Film coatings that are used on immediate-release products should utilize polymers that have good solubility in aqueous fluids to facilitate the rapid dissolution of the active ingredient from the finished dosage form following ingestion.  Film coatings used to modify the rate or onset of drug release from the dosage form tend to have limited or no solubility in aqueous media.  Polymers applied as solutions in a selected solvent should exhibit relatively low viscosities at the preferred concentration. This will help to facilitate easy, trouble-free spray application of the coating solution, especially in production-scale film-coating equipment. B. Plasticizer  Plasticizers are generally added to film-coating formulations to modify the physical properties of the polymer;  Increased film flexibility; and  Reduced residual stresses within the coating as it shrinks around the core during drying. Examples Some examples of commonly used plasticizers are:  polyols, such as polyethylene glycols and propylene glycol  organic esters, such as diethyl phthalate and triethyl citrate; and  oils/glycerides, such as fractionated coconut oil. C. Colourants  Pharmaceutically acceptable colourants are available in both water-soluble form (known as dyes) and water-insoluble form (known as pigments).  The insoluble form is preferred in film-coating formulations, because pigments tend to be more chemically stable towards light, provide better opacity and covering power, and provide a means of optimizing the permeability properties of the applied film coating. Examples  Iron oxide pigments  Titanium dioxide  Aluminium lakes D. Solvent/vehicle  Initially, film-coating processes were very much dependent on the use of organic solvents in order to achieve the rapid drying characteristics demanded by the process.  Organic solvents possess many disadvantages that are related to the following factors:  Environmental issues. The venting of untreated organic solvent vapour into the atmosphere  Safety issues. Organic solvents may be flammable (and thus explosive hazards)  Financial issues. Potentially unacceptable cost factors associated with the use of organic solvents  Solvent residue issues. Examples  methanol–dichloromethane combinations  acetone 2) Sugar coating  Sugar coatings are composed of ingredients that are readily soluble, or disintegrate rapidly, in water  In general, sugar-coated tablets are intended to exhibit immediate-release attributes.  Ideal characteristics of sugar-coated tablets  Sugar-coated tablets should possess a smooth, rounded contour, with even colour coverage and a glossy finish.  Typically, tablets are sugar coated by a panning technique, using a traditional rotating sugar-coating pan with a supply of drying air , and an extraction system to remove dust- and moisture-laden air ‫;‪Description of the sugar-coating process‬‬ ‫‪ Sugar coating is a multistage process and can be divided into the following steps:‬‬ ‫**خطوات عملية تغليف ا‪.‬قراص بالسكر‬ ‫‪**.1‬إغ‪9‬ق قلب القرص )‪:(Seal Tablet Core‬‬ ‫‪ -‬في هذه ا'رحلة‪ ،‬يتم تطبيق طبقة واقية على قلب القرص‪.‬تهدف هذه الطبقة إلى حماية ا'كونات الفعالة من‬ ‫العوامل البيئية مثل الرطوبة والضوء‪ ،‬مما يعزز من استقرار الدواء‪.‬‬ ‫‪**.2‬التغطية ا‪.‬ولية )‪:(Sub Coating‬‬ ‫‪ُ -‬تضاف طبقة أولية من السكر أو ا'واد ا‪Z‬خرى‪.‬هذه الطبقة تعمل كحاجز إضافي‪ ،‬وتساعد على تقليل التفاع‪a‬ت‬ ‫ب‪ b‬القلب وب‪ b‬طبقة السكر النهائية‪.‬‬ ‫‪**.3‬التنعيم )‪:(Smoothing‬‬ ‫‪ -‬يتم معالجة ا‪Z‬قراص بعد التغطية ا‪Z‬ولية لتسوية أي عيوب على السطح‪.‬تساهم هذه العملية في تحقيق ملمس‬ ‫أملس‪ ،‬مما يسهل بلع ا‪Z‬قراص ويعزز من جودتها‪.‬‬ ‫‪**.4‬التلوين )‪:(Colouring‬‬ ‫‪ُ -‬تضاف ألوان طبيعية أو صناعية إلى طبقة السكر‪.‬يهدف هذا إلى تحس‪ b‬جاذبية ا'ظهر الخارجي للقرص‪ ،‬مما‬ ‫يجعله أكثر قبوً‪ r‬للمستهلك‪.b‬‬ ‫‪**.5‬التلميع )‪:(Polishing‬‬ ‫‪ -‬بعد إضافة اللون‪ ،‬يتم تلميع ا‪Z‬قراص للحصول على 'سة نهائية ‪r‬معة‪.‬هذه الخطوة ‪ r‬تعزز فقط من ا'ظهر‪ ،‬بل‬ ‫ضا في حماية السطح من الخدوش والتلوث‪.‬‬ ‫تساعد أي ً‬ ‫‪**.6‬الطباعة )‪:(Printing‬‬ ‫‪ -‬في هذه ا'رحلة‪ ،‬يمكن طباعة معلومات إضافية مثل اسم الدواء أو الرقم التسلسلي على سطح ا‪Z‬قراص‪.‬تساعد‬ ‫هذه الخطوة في التعرف على ا'نتج وتوفير معلومات مهمة للمستخدم‪.‬‬ Description of the sugar-coating process; 1. Sealing  Sugar coatings are aqueous formulations; Hence water has an opportunity to penetrate directly into the tablet cores  To prevent these problems, the cores are usually sealed initially with a water-proofing or sealing coat. Examples  Traditionally, alcoholic solutions of shellac  Synthetic polymers, such as cellulose acetate phthalate or poly(vinyl acetate phthalate) 2. Subcoating  Sugar coatings are usually applied in quite substantial quantities to the tablet core (typically increasing the weight by as much as 50% to 100%) in order to round off the tablet edges.  such as adding calcium carbonate to the sucrose solutions. 3. Smoothing  The subcoating stage is notorious for producing a surface finish that is somewhat rough.  To facilitate the application of the colouring layer (which requires a smooth surface), subcoated tablets are usually smoothed out by applying a sucrose coating 4. Colouring  Colour coatings usually consist of sucrose syrups containing the requisite colouring materials.  Sugar-coating colourants may be subdivided into either water-soluble dyes or water- insoluble pigments.  Traditionally, water-soluble dyes have been used, but in order to speed up the coating process and minimize colour migration problems, dyes have gradually been replaced with pigments. 5. Polishing  Effectively polished to give characteristic shine, commonly using beeswax, carnauba wax. 6. Printing  For sugar-coated products, such identification can be achieved only by means of a printing process, which is typically an offset gravure process using special edible inks. Differences between sugar coating and film coating; 3) Compression coating  The process involves the compaction of granular material around preformed tablet cores  Compression coating is essentially a dry process Quality Standards And Compendial Requirements Quality Standards And Compendial Requirements  In addition to the apparent features of tablets, tablets must meet other physical specifications and quality standards. These include criteria for:  Weight  Weight variation  Content uniformity  Thickness  Hardness  Disintegration  Dissolution  These factors must be controlled during production (in-process controls) and verified after the production of each batch to ensure that established product quality standards are met Tablet Weight and USP Weight Variation Test  The quantity of fill in the die of a tablet press determines the weight of the tablet.  The volume of fill is adjusted with the first few tablets to yield the desired weight and content.  For example, if a tablet is to contain 20 mg of a drug substance and if 100,000 tablets are to be produced, 2,000 g of drug is included in the formula.  After the addition of the pharmaceutical additives, such as the diluent, disintegrant, lubricant, and binder, the formulation may weigh 20 kg, which means that each tablet must weigh 200 mg for 20 mg of drug to be present Tablet Weight and USP Weight Variation Test  Thus, the depth of fill in the tablet die must be adjusted to hold a volume of granulation weighing 200mg.  During production, sample tablets are periodically removed for visual inspection and automated physical measurement.  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. 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% of the label claim and the standard deviation is less than 6%.  If one or more dosage units do not meet these criteria, additional tests as prescribed in the USP are required. Tablet Thickness  The thickness of a tablet is determined by:  The diameter of the die  The amount of fill permitted to enter the die  The compaction characteristics of the fill material  The force or pressure applied during compression.  To produce tablets of uniform thickness during and between batch productions for the same formulation, care must be exercised to employ the same factors of fill, die, and pressure.  The degree of pressure affects not only thickness but also hardness of the tablet; hardness is perhaps the more important criterion since it can affect disintegration and dissolution. Tablet Hardness and Friability  It is fairly common for a tablet press to exert as little as 3,000 and as much as 40,000 lb of force  In production of tablets. 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.  Tablets should be sufficiently hard to resist breaking during normal handling and yet soft enough to disintegrate properly after swallowing. Tablet Hardness and Friability  Special dedicated hardness testers or multifunctional systems are used to measure the degree of force (in kilograms, pounds, or in arbitrary units) required to break a tablet.  A force of about 4kg is considered the minimum requirement for a satisfactory tablet.  A tablet’s durability: may be determined through the use of a friabilator.  A maximum weight loss of not more than 1% generally is considered acceptable for most products. Disintegration  The process of drug release from tablets often includes a step in which the tablet disintegrates into smaller fragments.  The test is performed by agitation of a given number of tablets in an aqueous medium at a defined temperature, and the time to reach the end point of the test is recorded.  The end point of the test is the point at which all visible parts of the tablets have been eliminated from a set of tubes in which the tablets have been held during agitation.  The tubes are closed at the lower end by a screen, and the tablet fragments formed during the disintegration are eliminated from the tubes by passing the screen openings Disintegration  All USP tablets must pass a test for disintegration, which is conducted in vitro using a testing apparatus.  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.  Tablets must disintegrate within the times set in the individual monograph, usually 30 minutes, but varying from about 2 minutes for nitroglycerin tablets to up to 4 hours for buccal tablets.  If one or more tablets fail to disintegrate, additional tests prescribed by the USP must be performed.  Enteric-coated tablets are similarly tested, except that the tablets are tested in simulated gastric fluid for 1 hour, after which no sign of disintegration, cracking, or softening must be seen. Dissolution  Dissolution testing is the most important way to study, under in vitro conditions, the release of a drug from a solid dosage form, and is thus an important tool to assess factors that affect the bioavailability of a drug from a solid preparation  Dissolution is accomplished by locating the tablet in a chamber containing a flowing dissolution medium.  All factors that can affect the dissolution process are standardized.  factors that affect the solubility of the substance; the composition and temperature of the dissolution medium  others that affect the dissolution process; (such as the concentration of dissolved substance in and the flow conditions of the fluid in the dissolution chamber). Dissolution  The composition of the dissolution medium might vary between different test situations;  Pure water or water mixed with acids or bases to adjust the pH  liquids showing a closer resemblance to physiological conditions may also be used. These are often referred to as simulated gastric or intestinal fluids or biorelevant fluids  Solvent mixtures, if the water solubility of the drug is very low  The main test methods are based on forced convection of the dissolution medium and can be classified into two groups: A. stirred-vessel methods B. continuous-flow methods. A. Stirred-vessel methods  The most important stirred-vessel methods; 1. The rotating-basket method 2. The paddle method Both use the same type of vessel, which is filled with a dissolution medium of controlled volume and temperature. In the paddle method, the tablet is placed in the vessel and the dissolution medium is agitated by a rotating paddle. In the rotating-basket method, the tablet is placed in a small basket formed from a screen. This is then immersed in the dissolution medium and rotated at a given speed. B. Continuous-flow methods  The preparation is held within a flow cell, through which the dissolution medium is pumped at a controlled rate from a large reservoir.  The liquid which has passed the flow cell is collected for analysis of drug content.  The continuous-flow cell method may have advantages over stirred-vessel methods, e.g. it maintains sink conditions through- out the experiment and avoids floating of the preparation. Tablet Thickness The thickness of a tablet is determined by: The diameter of the die The amount of fill permitted to enter the die The compaction characteristics of the fill material The force or pressure applied during compression. To produce tablets of uniform thickness during and between batch productions for the same formulation, care must be exercised to employ the same factors of fill, die, and pressure. The degree of pressure affects not only thickness but also hardness of the tablet; hardness is perhaps the more important criterion since it can affect disintegration and dissolution.  In vitro dissolution testing of solid dosage forms is important for a number of reasons :  It guides formulation and product development toward product optimization.  Dissolution studies in the early stages of a product’s development allow differentiation between formulations and correlations identified with in vivo bioavailability data.  Consistent in vitro dissolution testing ensures bioequivalence from batch to batch. ‫مثلية‬8‫نتج نحو ا‬4‫نية وتطوير ا‬/‫ توجيه التركيبة الصيد‬.1.‫ختلفة‬4‫نية ا‬/‫ التركيبات الصيد‬Q‫نتج يسمح بالتمييز ب‬4‫بكرة من تطوير ا‬4‫راحل ا‬4‫ إجراء دراسات الذوبان في ا‬-2.(in vivo) ‫( وبيانات الجاهزية الحيوية‬in vitro) ‫ختبر‬4‫ بيانات الذوبان في ا‬Q‫قات ب‬U‫ يمكن تحديد الع‬-.‫فضل‬8‫داء ا‬8‫نتج نحو ا‬4‫علومات توجه عملية تطوير ا‬4‫ هذه ا‬- :‫خرى‬8 ‫ ضمان التكافؤ الحيوي من دفعة‬-3.‫نتج‬4‫ختلفة من ا‬4‫ الدفعات ا‬Q‫ختبر بطريقة منتظمة يضمن التكافؤ الحيوي ب‬4‫ إجراء اختبارات الذوبان في ا‬-.‫طلوبة‬4‫نتج وأدائه وفًقا للمواصفات ا‬4‫ هذا يضمن استمرار جودة ا‬- A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet, including 1. Particle size of the drug substance 2. Solubility and hygroscopicity of the formulation 3. Type and concentration of the disintegrant 4. Binder 5. Lubricant 6. Manufacturing method 7. Particularly the compactness of the granulation 8. Compression force used in tableting 9. Any in-process variables Tablets Defects Capping  Capping happened when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during handling or other process.  Capping is usually due to; 1. Air–entrapment 2. Large amount of fines in the 3. Granulation 4. Too dry or very low moisture content 5. Insufficient amount of binder 6. Poorly finished dies and/or punches Lamination  Lamination is the separation of a tablet into two or more distinct horizontal layers.  Lamination is usually due to 1. Air-entrapment during compression 2. Too much of hydrophobic lubricant e.g. : Magnesium-stearate 3. Rapid decompression Sticking & Picking  Sticking is one of the most common problems of tablet making. It occurs when granules attach and stick to the faces of the punches instead of locking together to create a uniform tablet.  Picking is a specific type of sticking in which particles stick within the letters and logos that are embossed or debossed on the faces of the compression tooling  Reasons;  Weight variation  moisture content  particle size distribution  Bad quality of the punches  surface not smooth  Air entrapment Problems of Film Coating  Picking/ sticking: small holes pulled in film or small amount of the film flaking from the tablet surface.  Peeling: the coating peels away from the tablet surface or large amount of the film flaking from the tablet surface Problems of Film Coating;  Roughness: film not smooth  Twinning: two or more tablets that stick together. Common problem with flat or capsule shaped tablets Tablet Types Classification of tablets  A common means of classifying tablets is based on the pattern of drug release from the tablets (Immediate release tablets and Modified-release tablets) 1. Immediate release tablets.  For immediate-release tablets, the drug is intended to be released rapidly after administration, or the tablet is dissolved in liquid before intake and thus administered as a solution. Examples  Disintegrating tablets  Chewable tablets  Effervescent tablets  Sublingual tablets  Buccal tablets Disintegrating tablets  The most common type of tablet is intended to be swallowed and to release the drug a relatively short time thereafter by disintegration and dissolution,  A disintegrating tablet includes normally at least the following types of excipients: filler (if the dose of the drug is low), disintegrant, binder, glidant, and lubricant.  As discussed earlier, the drug is released from a disintegrating tablet in a sequence of processes, including tablet disintegration, drug dissolution and drug absorption  The rate of the disintegration processes and disintegration time are affected by both formulation factors and production conditions. Formulation factors;  The choice of disintegrant  The type of filler and lubricant  Coated tablets Production conditions;  the design of the granulation procedure  the mixing conditions during the addition of lubricants and antiadherents  the applied punch force during tableting and the punch force–time relationship. Chewable tablets  Chewable tablets, which have a smooth, rapid disintegration when chewed or allowed to dissolve in the mouth, have a creamy base, usually of specially flavoured and coloured mannitol.  Chewable tablets are especially useful for administration of large tablets to children and adults who have difficulty swallowing solid dosage forms. Effervescent tablets  Effervescent tablets are prepared by compressing granular effervescent salts that release gas when in contact with water.  These tablets 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. Buccal and sublingual tablets  Buccal and sublingual tablets are flat, oval tablets intended to be dissolved in the buccal pouch (buccal tablets) or under 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.  Buccal tablets are designed to erode slowly, whereas those for sublingual use (such as nitroglycerin) dissolve promptly and provide rapid drug effects. 2. Modified-release tablets  The term prolonged-release tablet is used to indicate that the drug is released slowly at a nearly constant rate. If the rate of release is constant during a substantial period, a zero-order type of release is obtained, i.e. M = kt (where M is the cumulative amount of drug released and t is the release time). Modified-release tablets;  A pulsatile release is another means to increase the period of drug absorption after a single administration and is accomplished by releasing the drug in two or more pulses.  Delayed-release tablets, the drug is liberated from the tablet some time after administration. After this period has elapsed, the release is normally rapid.  The most common type of delayed-release tablet is a gastro-resistant (also known as enteric-coated) tablet Modified-release tablets; Prolonged-release and pulsatile-release tablets  In recent years there has been great interest in the development and use of tablets which should be swallowed and thereafter slowly release the drug in the gastrointestinal tract for approximately 12–24  The aims are normally;  To increase the time during which a therapeutic drug concentration in the blood is maintained.  To increase the release time for drugs that can cause local irritation in the stomach or intestine if they are released quickly.  Prolonged-release tablets are often categorized according to the mechanism of drug release.  The following are the most common means used to achieve a slow, controlled release of the drug from tablets:  Drug transport control by diffusion  Dissolution control;  Erosion control  Drug transport control by convective flow (accomplished by, for example, osmotic pumping) Diffusion-controlled release systems  Diffusion-controlled release systems are divided into; 1) Matrix systems 2) Reservoir systems.  In matrix systems, diffusion  In reservoir systems, diffusion occurs in a occurs in pores located within thin water-insoluble film or membrane, the bulk of the release unit, often approximately 5 μm to 20 μm thick, which surrounds the release unit. Drug is released from a diffusion-controlled release unit in two steps: 1. The liquid that surrounds the dosage form penetrates the release unit and dissolves the drug. A concentration gradient of dissolved drug is thus established between the interior and the exterior of the release unit. 2. The dissolved drug will diffuse in the pores of the release unit or the surrounding membrane and thus be released or, alternatively, the dissolved drug will partition into the membrane surrounding the dose unit and diffuse in the membrane. The rate at which diffusion will occur depends on three variables: 1. The concentration gradient over the diffusion distance 2. The area and distance over which diffusion occurs; 3. The diffusion coefficient of the drug in the diffusion medium. ‫‪.1‬اختراق السائل ا‪+‬صفوفة و إذابة الدواء‪:‬‬ ‫ السائل ا‪+‬حيط بالشكل الصيد

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