Advantages And Disadvantages Of Tablets In Pharmaceutical Industry

Advantages And Disadvantages Of Tablets In Pharmaceutical Industry Introduction Tablets are solid dosage forms usually containing active pharmaceutical ingredient and excipients in powder, crystalline or granular form with or without diluents which is prepared either by moulding or compression process. They are solid, biconvex or flat in shape and vary in size, shape and weight which is depends on the medicaments which are used for preparation. They are also varying in hardness, disintegration; dissolution characteristics and thickness depend on their intended use and method of manufacture. Tablets are the most widely used solid dosage forms because of their advantages and popularity increasing day by day. Tablet usually contains filler, diluents, binders, lubricants, glidants, disintegrants, antiadherent, colouring agents and flavouring agents as excipients.[Ansels Pharmaceutical Dosage Forms and Drug Delivery Systems, Eighth Edition, Loyd V. Allen, Jr, Nicholos G. Popovich, Howard C. Ansel, 2005, pp-228-245] Advantages of tablets Unit dosage forms with accurate, stable dose and great precision and least variability. Most stable with respect to physical, chemical and microbiological attributes. Cheapest oral dosage form, easy to handle, use and carry out with attractive and elegant appearance. Cheap, easy to swallow and production does not require and additional processing steps. Provide protection of medicaments from atmospheric conditions like air, moisture and light, etc. Provide prolonged stability to medicaments. Low manufacturing cost as compare to other solid dosage forms and large scale production is possible. Administration of minute dose of drug in accurate amount. Unpleasant taste can be masked by sugar coating. Easy to divide into halves and quarters whenever fraction dose is required. Formulate as a special release products such as enteric or delayed release products. Packing and production is cheap and does not require more space for storage. Disadvantages of tablets Drugs which are amorphous and low density character are difficult to compress into tablet. Hygroscopic drugs are not suitable for compressed tablets. Drugs with low or poor water solubility, sloe dissolution, high absorbance in GI tract may be difficult to formulate. Sensitive to oxygen drugs may require special coating. Cost of production may be increase because of coating and encapsulation to remove bitter and unpleasant taste. Some tablet may cause problem in bioavailability. Difficult to formulate liquid in tablet and swallowing is difficult especially for children and ill patients. Types of tablets There are many types of tablets according to the intended of use and manufacturing process. [A] Oral tablet intended for ingestion Compressed tablets: Tablets can be made by compression of one or more active pharmaceutical ingredient with excipients by basic methods of tablet manufacturing. These types of tablets usually intended to provide raid drug release and disintegration. Tablets are coated after compression. Multiple compressed tablets: Multiple compressed tablets are prepared by compressing the material more than once. These are known as multiple layered tablets or tablet within tablet. Layered are depends on number of fills. Layered tablets are prepared by compaction of fill material in die followed by additional of fill material and compression. Delayed action or Enteric coated tablets: These types of tablets contain a coating which resist dissolution of tablets in Gastro Intestinal Track (GIT) and disintegrate in intestinal fluids thus rendering delayed release features. Enteric coating is generally apply when drug substance is unstable in gastric fluid and may destroyed or may cause irritation in gastric mucosa or to extent absorption of drug from intestine. Normally coating materials mixed with acid and acid functionality or modified natural polymers. Most commonly used coating polymers are: Cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP) and hydroxyl propyl methyl cellulose phthalate. Sugar coated tablet: Compressed tablets may be coated with coloured or uncoloured sugar coating and the coater is water soluble and dissolve quickly after swallowing. Sugar coat protects drug from environment, remove bitter taste and odour, enhance the appearance of tablet and permit identifying information. Sugar coating has some disadvantages like increase coat of production, require expertise for coating, increase size and weight. Film coated tablets: Tablets are compressed with a thin layer of polymer which forms a skin like film over tablet. The film is usually coloured, more durable and less bulky. The coating is designed to rupture and expose of tablet at desired location within GIT. Most commonly used polymers are Hydroxy propyl cellulose, Hydroxy ethyl and propyl methyl cellulose. Chewable tablet: These types of tablets have smooth surface, creamy base and usually flavoured and coloured mannitol, rapid disintegration which allow dissolving quickly in mouth. These types mostly useful for administration of large dose to children and adults. [B]Tablet used for oral cavity Buccal tablets and sublingual tablets: Buccal and sublingual tablets are flat in shape and intended to dissolve drug in buccal cavity or beneath the tongue for mucosa absorption. These techniques useful for drugs which are destroyed by gastric fluid or poor absorption in GIT. Buccal tablets erode slowly and sublingual tablets dissolve quickly and produce rapid effect. Troches and Lozenges: They are intended to slowly dissolution mostly for local effect but sometimes for systemic absorption. Troches and Lozenges are disc shaped which contain active ingredient and flavouring agent in hard candy or sugar base. Dental cones: dental cones are designed to place in the empty socket for prevention of bacterial growth and sometime bleeding by containing coagulant. Dental cones release slowly for long duration. [C] Tablets for other routes Vaginal tablet: Vaginal tablets are prepared by compression and shaped to fit snugly on plastic inserter devices in uncoated bullet shaped or ovoid tablets which are inserted into vagina for local effects with slow dissolution. They contain anti bacterial effect and also called vaginal inserts. Implantation tablet: Implantation tablets are injected under the skin by giving a small surgical cut into the skin. A special injector a hallow needle and plunger may require for administration. Purpose of these tablets is to prolong drug effect from month to year. These tablets are implanted intramuscularly or subcutaneous so they must be sterile and packed in sterile container. [Pharmaceutics I, P.V. KASTURE, S.R. PARAKH, S.A. HASAN, S.B. GOKHALE, June 2008, pp-14-7,21] [D] Tablets for solution Effervescent tablet: Effervescent tablets prepared by compression of granular salts which release in contact with water. Dispensing tablets: These types of tablets are no longer use because they had dangerous potential. They might be termed compounding tablets because it contain highly potent drug and pharmacist use it for compound prescription. Hypodermic tablets: Hypodermic tablets are soft moulded tablets which contain soluble ingredient and used for extemporaneous parenteral preparation by physician. They are no longer in use because it is difficult to achieve sterility and availability of stable liquid. Tablet triturates: tablet triturates are rarely use now a days because they are obsolete. They are small, cylindrical, molded which contain small amount of potent drug. They must be readily soluble in water and minimum amount pressure require during manufacture. Triturates inserted into capsules or dissolved in liquid to provide accurate potent drug. Tablet Excipients: Excipients are substance other that active ingredient in formulation of tablet. The roles of excipients are to ensure tabletting operation satisfactory and ensure that tablets of specified quality are prepared. Depend on intended use; they are subcategorised in different groups. However excipients affect properties of tablets. Diluents or filler A small amount of powder requires forming suitable size tablet for easy handling. Normally tablet weigh 50mg so some amount of bulk drug requires to incorporation in formulation of tablet which enhance size of tablet. These powders known as diluents or fillers. The ideal dilute should have following properties- cheap, chemically inert, acceptable taste, good compactability and dilution capacity, biocompatible, good biopharmaceutical properties and non hygroscopic. A single substance cannot fulfil all these requirements so different substance have gained use as diluents mainly carbohydrates and inorganic salts sometimes. The most common diluent is lactose because it possess a sires of good properties like dissolves readily in water, has a pleasant taste, non hygroscopic is fairly non reactive and shows good compact ability. Its main limitation is that some people have intolerance to lactose. Basically lactose exists in two forms crystalline and amorphous. Other sugar and sugar alcohols such as glucose, sucrose, and mannitol have been used as alternative fillers, mostly in chewable tablets or lozenges because of their pleasant taste. Other important example of the filler is an inorganic substance, dicalcium phosphate dehydrate. It is insoluble in water and also non hygroscopic but have hydrophilic property i.e. easily wetted by water. It also has good flow ability and therefore it is used mostly in direct compaction. [Michael, Pharmaceutics: the design and manufacture of medicines.- 3rd ed. Edinburgh : Churchill Livingstone, 2007.] [ Leon Lachman, Herbert A. Lieberman and Joseph L. Kanig. (1991). the theory and practise of industrial pharmacy. 3rd addition: Varghese publishing house. Page no. 293- 303.] Disintegrants: According to Michael, 2007, a disintegrant is added in formulation of tablet, which promotes drug dissolution and provide an effective surface area, when comes in contact to liquid and breaks down in small fragments. The process of disintegration for tablet occurs in main two steps [1] Tablet wets by sold and pores it [2] Breaks down of tablet into small fragments which include aggregation of primary particles into small drug particles. Disintegrant suggested in some mechanism such as swelling of particles, wetting reaction, repulsion of particle and particle recovery. Most common types of disintegrants in tablets are maize, potato and corn starch. the concentration of starch is up to 10% required but today normally modified starch or modified cellulose are used which are very high swelling disintegrants. So its requires typically 1-5% by weight which facilitate particle-particle repulsion. However, disintegrants can be mixed with other ingredients such as granules to increase effective disintegration of the tablet into smaller fragments. Leon Lachman et al, 1991, suggested that other group of disintegrants may function by producing gas, normally carbon dioxide, in contact with water. This types of disintegrants used in effervescent tablets and normally not in tablets that should be swallowed as a solid. The liberation of carbon dioxide is achieved by the decomposition of carbonate salts or bicarbonate in contact with acidic water. The acidic pH is obtained by adding citric acid and tartaric acid. [ Michael, Pharmaceutics: the design and manufacture of medicines.- 3rd ed. Edinburgh : Churchill Livingstone, 2007. 3. Leon Lachman, Herbert A. Lieberman and Joseph L. Kanig. (1991). the theory and practise of industrial pharmacy. 3rd addition: Varghese publishing house. Page no. 293- 303] Binder Binder is added to the tablet or filler mixture to ensure that tablets and granules have sufficient mechanical strength. There are several ways to add it in powder- Mixed with powder before wet granulation which completely or partially dissolves during agglomeration process by agglomeration liquid. Mixed with other ingredient as a dry powder solution before compaction process As a solution used as agglomeration liquid during wet granulation. Typically 2-10% of binders or dry binders are used in formulation. Most tradition common binders are starch, sucrose and gelatine but now most common are polyvinylpyrrolidone and cellulose derivatives which have improved adhesive properties. Examples of dry binders are microcrystalline cellulose and crosslinked polyvinylpyrrolidone. Solution binders are most effective therefore it is incorporated in granules. Glidant The role of the Glidant is to improve the flow ability of the powder. Glidants are used in formulation for direct compaction but they are also used in granulation process before tabletting which ensure flow ability of tablet mass for high speed production. Traditionally talc has been used as glidant about 1-2% concentration in formulation but nowadays the most commonly used glidant is colloidal silica added in very low proportion about 0.2% by weight.[ Michael, Pharmaceutics: the design and manufacture of medicines.- 3rd ed. Edinburgh : Churchill Livingstone, 2007. 3. Leon Lachman, Herbert A. Lieberman and Joseph L. Kanig. (1991). the theory and practise of industrial pharmacy. 3rd addition: Varghese publishing house. Page no. 293- 303] Lubricant The function of lubrication is to ensure low lubrication between solid and the die wall during tablet formation and ejection. High friction during tabletting can cause a series of problems such as inadequate tablet quality and may even stop production. Lubrication is most important which included in most of production. Lubrication can get by mainly two mechanism, fluid lubrication and boundary lubrication. In fluid lubrication, liquid is achieved between die surface and tablet surface which separates the moving surfaces of the solids from each other and reduces the friction. While in boundary lubrication, it is considered as a surface phenomenon, as here moving surface is separated by a very thin layer of lubricants. Such boundary lubricants are Stearic acid salts, primarily Magnesium Stearate which is most widely use due to its superior lubrication properties. Besides reducing friction, lubricants may also causes undesirable changes such as reducing tablet strength with bonding between the particles during compaction. Because of hydrophobic properties of lubricants, tablet disintegration and dissolution are often retarded by the addition of lubricants. Thus, minimum amount of lubricants are used, i.e. concentrations of 1% or below, often 0.25-0.5%.in order to avoid these negative effects, more hyd rophilic substances have been suggested as alternatives to the hydrophobic lubricants. For example, surface active agents and polyethylene glycols and sometimes a combination of hydrophilic and hydrophobic substances might also be used. [M. E Aulton, Pharmaceutics, The Science of Dosage Form Design, Second Edition, 2002, pp.408-412] Antiadherent Antiadherent are substance which reduce adhesion between powder and punch faces which prevent sticking of particles to punches. The sticking is mainly affected by moisture content of the powder. Such adherence especially prone to happen if the tablet punches have marking or symbols which lead to a build of thin layer of powder on the punches which in turn will lead to an uneven and matt tablet surface with unclear markings or symbols. Some lubricants such as Magnesium Stearate have also antiadherent properties. However, other substances with limited ability to reduce friction can also act as antiadherent such as talc and starch. [M. E Aulton, Pharmaceutics, The Science of Dosage Form Design, Second Edition, 2002, pp.408-412] Sorbents Sorbents are substances which has capacity to sorbing some quantities of fluid into dry state. So oil and oil-drug solutions can be incorporated into mixture of powder and compacted into tablets. Most commonly used sorbents are Microcrystalline Cellulose and Silica. [M. E Aulton, Pharmaceutics, The Science of Dosage Form Design, Second Edition, 2002, pp.408-412] Flavouring agents Flavouring agents are incorporated into a formulation to remove unpleasant taste of bitter drug or to make tablet more pleasant or mask. This can be achieved by coating or by adding some drug particles. Most of Flavouring agents are thermolabile so it cannot be added in process which involve heating. They are mixed with granules as alcoholic solution. Colouring agents The aim to add colourant is to aid identification of tablet, improve looks of tablet and patient compliance. Mostly, colourant are added during coating of tablet but some of colourant may be added in formulation prior to compaction. Colourant may be added as an insoluble powder or dissolved in granulation liquid and the latter procedure may produce colour variation by migration of soluble dye during drying stage. Method of tablet preparation Three types method of tablet preparation- [1] Direct compression method [2] Wet granulation [3] Dry granulation Direct compression method Some chemicals have free flowing and cohesive properties so they are enable to compress directly in a tablet machine without granulation of it. Some chemicals lacking of these qualities so some excipients like filler, disintegrants agents, lubricants and glidants are used to impart these qualities for production of tablets by direct compression. Figure (A) Steps of direct compression tableting Some precaution must be taken during direct compression to avoid air entrapment which cause capping, splitting, or laminating of tablets. Forced feeders or induced feeders are used to reduce air entrapment, make filling powder more dense and amenable to compaction. Capping also may be caused by punches that are not perfectly clean and flawlessly smooth or by too much fines granulation. Some aged or improperly stored tablets also may exhibit splitting and other physical deformations. Wet granulation Granulation is process in which primary powder particles are made to form large and these types of multi particle called granules. In pharmaceutical industry, granules are useful in production of tablets and capsules in ranges of particle size between0.2 to 0.5mm. Granulation prevents segregation of constituents of powder, improve flow ability of powder, improve compaction characteristics of mixture and reduce toxic dust. Wet granulation is widely used method for production of compressed tablets which include flowing steps- Weighting and blending In this step, specified quantities of active ingredient, diluents or fillers, and disintegrating agents are mixed by mechanical powder blender or mixture until uniform. Most widely used fillers are lactose, microcrystalline cellulose, starch, powdered sucrose, and calcium phosphate. Selections of filler depend on the experience of manufacture, cost and compatibility with formulation. Among the fillers, lactose is most preferred because of its solubility and compatibility, and microcrystalline cellulose, because of its easy compaction compatibility and consistent uniformity of supply. Disintegrating agents include croscarmellose, corn and potato starches, sodium starch glycolate, sodium carboxymethylcellulose, polyvinyl polypyrrolidone (PVP), cation exchange resins, alginic acid and other materials which swell or expand on exposure to moisture and helps to breakup tablets in gastrointestinal track (GIT). Mainly croscarmellose and sodium starch glycolate are used because of their high water uptake and rapid action. Mostly up to 5-10% of starch is suitable for formulation, but up to about 20% may be used to facilitate more rapid tablet disintegration. The total amount of disintegrant is not always used but sometime it added in preparation of granulation and sometime half of it added to tablet formation which called double disintegration of tablet. One portion of disintegrant assist breakup of tablet into pieces and other portion breakup pieces into particles. Preparation of Damp Mass A liquid binder is now added to the powder to facilitate adhesion of powder particles. A damp mass resembling dough is formed and used to prepare the granulation. A good binder is very important for hardness of tablet and does not hinder the release of drug from the tablet. Most widely used binders are povidone, an aqueous preparation of corn starch (10-20%), methyl cellulose (3%), carboxymethylcellulose, and microcrystalline cellulose. Some drugs may be adversely affected by an aqueous binder then non-aqueous solutions or dry binder may be used. The amount of binders is a part of operation which maintains integrity of tablet after compression. However, care must be exercised not to over or underwet powder otherwise underwet can result too hard granules for proper tablet formulation and overwet can result too soft and tend to crumble in under wetting. After getting desired dump mass a colorant or flavorant may be added to prepare a granulation with an added features. Screening Damp Mass into Pellets and Granules The Dump Mass is pressed through 6 or 8 mesh size to prepare granules. This process may be done by hand or by special equipment which prepares granules by extrusion process. The final product are spread on large piece of paper in trays and dried. Drying the granulation Granules may be dried in special drying cabinets which is thermostatically controlled at constantly record the time, temperature and humidity. Fluid bed drier and tray drier are commonly used for during process. Sizing the granulation by Dry Screening After drying, the granules are passed through a screen of a smaller mess than that used to prepare the original granulation. The size of granules depends upon the size of the punches to be used. Usually 12 to 20 mesh sizes are used for granulation. Sizing of the granules is necessary so that the die cavities for tablet compression may be completely or rapidly filled by the free flowing granules. Voids or air spaces left by too large a granulation result in production of uneven tablets. Adding Lubrication and Blending After dry screening, a dry lubricant is spread over the granulation through a fine mess screen which contributes to preparation of compressed tablets. Among the most commonly used lubricants are talc, magnesium stearate, calcium stearate, stearic acid, and sodium stearyl fumarate in ranges of 0.1% to 5%. Lubricants improve flow property of granules form hooper ti die, prevent adhesion during compaction, reduce friction between die and punch and provide a sheen final product. Figure (B) Tablet compression by wet granulation [Pharmaceutics I, P.V. KASTURE, S.R. PARAKH, S.A. HASAN, S.B. GOKHALE, June 2008, pp-14-7, 21] Some special wet granulation techniques High shear mixture granulation Fluid bed granulation Extrusion- spheronisation Spray drying Dry granulation In this method, powder mixer is compressed in large pieces and subsequently broken down or sized into granules. In this method, either active ingredient or diluent must have cohesive properties. This method is basically applied to materials which cannot be prepared by wet granulation because of moisture degradation properties or thermo-mobile properties of granules. It is carried out by two steps: Slugging: After weighing and the mixing of ingredients, the powder mixture is slugged or compressed into large flat tablets about one inch in diameter. Slugs are than broken up hand or mill and passed through a screen of desired mess for sizing and sometimes lubricant are added and prepared by compression. Roller compaction: Instead of slugging, powder compactors may be used to increase the density of a powder by pressing it between rollers at 1 ton to 6 tons of pressure. The compact material is broken up, sized, and lubricated, and tablets are prepared by compression. Commonly used binding agents are methyl cellulose or hydroxylmethyl cellulose (6-12%) which produces good hardness and friability of tablet. Figure (C) Tablet compression by Dry Granulation [Pharmaceutics I, P.V. KASTURE, S.R. PARAKH, S.A. HASAN, S.B. GOKHALE, June 2008, pp-14-7, 21] Tableting of granulation: There are different types of tabletting machines which are used in the productivity but similar in basic function and operation. They all compress tablet formulation within steel die cavity by the pressure exerted by the movement of two steel punches, lower punch and an upper punch. Problems in manufacture of tablet Capping and lamination: Capping means partial and complete separation of the top or bottom crowns of a tablet from main body of a tablet. While lamination is term used to describe the separation of the two or more distinct layers. Some reasons which are responsible for these problems are as follows: Air is entrapped among the particles during the compression process and does not escape until compression pressure is released. Die wall pressure causes enough internal stress to cause a crack which is due to plastic deformation of the particles during compaction. Sometimes due to deep concave or bevelled edge punches. Development of wear ring. This problem can reduced or eliminated by slowing tabletting rate, granules with sufficient moisture, pre-compression, using flat punches, correct adjustment punches. [Porter, S C, 1981, Tablet coating, Drug Cosmetic Indu, May 46, June 44, Aug 40, Sept 50] Weight variation: This is very important in process control measurement. If anything that can alter the die filling process can alter tablet weight, it causes weight variation because the weight of the tablet being compressed is determined by the amount of the granulation in the die prior to compression. Some causes of variation are large granules, poor mixing of granules with lubricants and glidants, poor granulation flow from hopper, double impression and punch variation. Picking Picking is the term used to describe the surface material from tablet that is sticking to being removed from the tablets surface by a punch. It concerns when punching tips have engraving or embossing Sticking Sticking is usually referred to adhesion of tablet material to die wall. Because of that, lower punch cannot move freely and additional force is required to overcome friction between die wall and the tablet. These problems can be solved by design large lettering, adding polishing agent such as colloidal silica or additional lubricants. Some low melting point substances such as polyethylene glycol may also cause sticking at the heat of compression. Such Remedies are addition of high melting point materials and consequently increasing size of tablet. Mottling: Mottling is term used unequal distribution of colour on a tablet with light and dark areas. Its due to colour difference of drug with excipients or drugs whose degradation product is coloured. Such problems might be solved by using colorants but it can cause mottling on the top of surface when granulation undergoes drying. To overcome difficulties, it require to change solvent system, binder system and by reducing temperature. Tablet coating Tablet coating is application of coating of material to the exterior of tablet with some intentional benefits. It is also intended for modified release applications. Main three types of coating are- Film coating Sugar coating Press coating Coating of tablets are for following purposes- [1] Protection from environment, light and moisture [2] To remove bitter taste of some tablets and for easy swallowing of tablets [3] Colour coating mask differences in appearance which effect on patient compliance [4] Rapid identification by manufacturer, pharmacist and patient [5] Functional films can enable sustained and enteric protection [6] Improve looks (elegance), masks and minor difference in raw material appereance [7] Enhance strength, reduce dust and cross contamination Film coating This is more modern and widely used for tablet coating. Most of newly launched coated products are film coated rather than sugar coating. Film coating involves covering of tablet by thin film layer of coating liquid (polymer). Coating liquid is sprayed in a rotating tablet bed or bed fluidised tablet which contains plasticizer, polymer, colourant and solvent. The drying condition permits removal of solvent and leaves a thin layer around each tablet. Sometimes aqueous solution or organic solutions are used to reduce elimination of volatile organic compound, health and safety and cost reduction purposes. Film coating polymer should have following properties- [1] Optimum solubility to facilitate dissolution of final product. High soluble for immediate release and low soluble for controlled release. [2] Optimum viscosity to permit and trouble free spraying of solution. [3] Optimum permeability to optimize shelf life of tablet preparation and some tuned to provide an effective barrier oxygen and water vapour. [4] Good mechanical strength to withstand the impact and abrasion encountered in normal handling which avoids cracks and imperfections. Cellulose derivatives like Hydroxypropylmethylcellulosa (HPMC), methylcellulose, hydroxypropylcellulose (HPC) and Methacrylate amino ester copolymer are available polymer for film coating. Sugar coating Sugar coating involves the successive application of sucrose based solutions to tablet cores in suitable equipment. Some stages in production of sugar coated tablets are- [1] Sealing of tablet core- provide water proofing core from coating process and shellac, cellulose acetate phthalate are normally used in sealing process. [2] Sub coating- it is the actual start of sugar coating which provides necessary build-up to roundup the tablet edge. Bulking agents such as calcium carbonate or talc added in sucrose solution with gum. [3] Smoothing it increases tablet size to predetermined dimension by syrup solution. This solution contains pigments, starch, gelatine, acacia or opacifier. [4] Colouring- dyes or pigments [5] Polishing- tablets need to be polished to achieve final elegance by waxes like beeswax, carnubawax or hard paraffin. [6] Printing Difference between sugar and film coating Press coating Press coating involves compaction of granules material around core of tablet with the use of compressing equipment like Manesty Drycota. Today press coating is used in to separate incompatible placed core and coating layer. This process requires some care and large or irregularly sized agglomerate of granules may cause core to tilt in die. Disadvantages of process arise from complexities of mechanism used in compression equipment. [M. E Aulton, Pharmaceutics, The Sc