Solid Dosage Forms: Tablets

Tablets are solid dose pharmaceutical preparation containing drug substances usually prepared with the aid of suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture.

Tablets constitute approximately 90% of all dosage forms clinically used to provide systemic administration of therapeutic agents. This widespread use of tablets has been achieved as a result of their convenience and also the diversity of tablet types.

Tablets are prepared primarily by compression of granules or powder blends, with a limited number prepared by moulding. Most tablets are used in the oral administration of drugs. Many of these are prepared with colourants and coatings of various types. Other tablets, such as sublingual, buccal, or vaginal tablets, are prepared to have features most applicable to their particular route of administration.

General Properties of Tablets

• A tablet must be strong and hard to withstand mechanical shock during manufacturing, packing, shipping, dispensing and use.
• The drug content of the tablet must be bioavailable that is, the tablet must be able to release its content in a predictable and reproducible manner.
• The tablet must be chemically and physically stable to maintain its chemical and physical attributes during manufacture, storage, and use.
• The tablet should have elegant product identity which is free from any tablet defect.
• Tablets must be uniform in weight and in drug content.

Types of tablets

The various tablet types are described as follows:

a. Compressed tablets

Compressed tablets represent a significant proportion of tablets that are clinically used to provide systemic administration of therapeutic agents either in an uncoated state (i.e., in their simplest form) or in a coated state. These tablets are designed to provide rapid disintegration in the gastric fluid following ingestion hence, allowing rapid release of the drug and, ultimately, systemic absorption of the dosage form.

Compressed tablets are formed by compression of powdered, crystalline, or granular materials into the required geometry by the application of high pressures, utilizing steel punches and die. In addition to the Active Pharmaceutical Ingredient(s) (APIs), compressed tablets usually contain a number of pharmaceutical excipients e.g., bulking agents, disintegrants, binders, lubricants, controlled-release polymers and other miscellaneous adjuncts such as colourants and flavourants which serve different and specialized purpose during tablet manufacture, storage, and use. Examples of compressed tablets include tablets for oral, buccal, sublingual, or vaginal administration.

b. Sugar-coated Tablets

These are compressed tablets that have been coated with concentrated sugar solution to improve patient’s compliance, increase aesthetic appeal, mask objectionable tastes or odours, increase stability and/or modify the release of therapeutic agent(s). Sugarcoating was once quite common but lost commercial appeal due to the time and expertise required in the coating process, the increase in size and weight of coated tablets, high cost of process validation and shipping.

The advent of film-coated tablets has also greatly decreased the use of sugar coatings due to the improved mechanical properties of the technique. Examples of sugar-coated tablets include Reasulf tablets – dried ferrous sulphate BP 200mg (Reagan Remedies Ltd.), Advil – Ibuprofen tablet BP 200mg (Pfizer Consumer Healthcare), Ebu-200 – Ibuprofen tablet BP 200mg (Me cure Industries Ltd) etc.

c. Film-Coated Tablets

Film-coated tablets are conventional tablets coated with a thin layer of polymer (e.g., hydroxypropyl methylcellulose, hydroxypropyl cellulose) or a mixture of polymers (e.g., Eudragit E100) capable of forming a skin-like film. The film is usually coloured and also impacts the same general characteristics as sugar coating with the added advantage of being more durable, less bulky, and less time-consuming to apply. By its composition, the coating is designed to break and expose the core tablet at the desired location in the gastrointestinal tract.

Advances in material science and polymer chemistry have made these coatings the first choice for formulation scientists. Examples of Film-coated tablets include Curefenac 100 – Diclofenac potassium USP 100mg (Unicure Pharmaceutical Ltd), Valsartan 320mg Film-coated Tablets (Actavis UK Ltd), etc.

d. Effervescent Tablets

Effervescent tablets are uncoated tablets that generally contain organic acids (such as tartaric or citric acid) and sodium bicarbonate in addition to the medicinal substance or API.  They react rapidly in the presence of water by releasing carbon dioxide which acts as a disintegrator to produce either a drug suspension or an aqueous solution. These tablets are prepared by compressing granular effervescent salts (organic acid and bicarbonate) with the medicinal substances. A typical example of this tablet type is Ca C1000 Sandoz effervescent tablet (Novartis).

e. Enteric-coated Tablets

Enteric-coated tablets are compressed tablets that have delayed-release properties. They are coated with polymeric substances (such as cellulose acetate phthalate/cellulose acetate butyrate; hydroxypropylmethylcellulose succinate; and methacrylic acid copolymers) that resist solution in gastric fluid but disintegrate and allow drug dissolution and absorption in the intestine.

Enteric coatings are primarily employed when the drug substance is inactivated or destroyed by gastric acid (e.g., erythromycin) or is particularly irritating to the gastric mucosa (e.g., non-steroidal anti-inflammatory drugs) or when bypass of the stomach substantially enhances drug absorption. Example of enteric-coated tablets includes Lofnac 100 – Diclofenac sodium delayed-release tablet USP 100mg (bliss GVS Pharma Ltd), Ecotrin tablets and caplets (GlaxoSmithKline Beecham).

f. Chewable Tablets

Chewable tablets are big sized tablets which are difficult to swallow and thus, are chewed within the buccal cavity prior to swallowing. They are especially useful for administration of large tablets to children and adults who have difficulty swallowing conventional tablets or antacid formulations in which the size of the tablet is normally large and the neutralisation efficacy of the tablet is related to particle size within the stomach.

Chewable tablets are not conventionally used if the drug has issues regarding taste acceptability. Examples of chewable tablets include Danacid – compound magnesium trisilicate tablet B.P. (Dana Pharmaceuticals Limited), Gestid – tasty chewable antacid (Ranbaxy) etc.

g. Buccal and Sublingual Tablets

Buccal and sublingual tablets are small, flat, oval tablets that are intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for absorption through the oral mucosa to produce a systemic effect. These tablets are employed to achieve either rapid absorption into the systemic circulation e.g. glyceryl trinitrate sublingual tablets or, alternatively, to enable oral absorption of drugs that are destroyed by the gastric juice and/or are poorly absorbed from the gastrointestinal tract.

h. Lozenges or Troches

These are disc-shaped solid preparations containing medicinal agents and generally a flavouring substance in a hard candy or sugar base. They are intended to be slowly dissolved in the oral cavity, usually for local effects.

Examples include Strepsils Dry Cough Lozenges – Dextromethorphan Hydrobromide 5mg, Dichlorobenzyl alcohol 1.2mg, Amylmetacresol 0.6mg (Reckitt Benckiser), Dequadine – Dequalinium chloride BP 250mcg (Evans Medical PLC), Dr Meyer Coflin cough lozenges (Meyer Organics PVT Ltd), Cofta – Ammonium chloride/ Ipecacuanha tablet (Evans Medical PLC) etc.

i. Tablet Triturates

Tablet triturates are small, usually cylindrical, moulded, or compressed tablets containing small amounts of usually potent drugs mixed with a combination of sucrose and lactose or any suitable diluent. They are prepared from moist material, using a triturate mould that gives them the shape of cut sections of a cylinder.

Since tablet triturates must completely and rapidly dissolve in water, only a minimal amount of pressure is applied during their manufacture. One of the problems encountered during the manufacture of this tablet type is the failure to find a lubricant that is completely water-soluble. A typical example of tablet triturate is NTG tablets.

j. Hypodermic Tablets

Hypodermic tablets are soft, readily soluble tablets that were originally used by physicians in extemporaneous preparation of parenteral solutions. These tablets are dissolved in a suitable vehicle (water for injections) and administered by parenteral route.

Hypodermic tablets are no longer used in most countries due to the difficulty in achieving sterility. Also, the availability of stable parenteral solutions and prefabricated injectable products, some in disposable syringes have also discouraged their use in recent times. e.g., Dilaudid – Dihydromorphinone HCl (Bilhuber Knoll Corp.).

k. Dispensing Tablets

Dispensing tablets also referred to as compounding tablets are tablets supplied primarily as a convenience for extemporaneous compounding. These tablets contain large amounts of highly potent APIs, and thus are used by a pharmacist to compound prescriptions that can be incorporated readily into powders and liquids, thus, circumventing the necessity to weigh small quantities of these potent drug substances.

Dispensing tablets are no longer in use and had the dangerous potential of being inadvertently dispensed as such to patients. Examples include silver potentiate, bichloride of mercury merbromin and quaternary ammonium compounds.

l. Gelatin-Coated Tablets

Gelatin-coated tablets are compressed tablets coated with either one or two-toned colour gelatin. The gelatin coating impacts the same general characteristics as sugar coating and film coating with the added advantage of improving the stability of photosensitive APIs.

The gelatin coating also facilitates swallowing, enables custom branding,  and prevents counterfeit since they are more tamper-evident than unsealed capsules. Gelatin-coated tablets are also ideal for double-blind clinical studies, or for drug substances that can irritate the oesophagal mucosa when they are incorporated in an immediate-release tablet such as bisphosphonates.

Example of gelatin-coated tablets includes gelatin-coated hydrochlorothiazide tablet (Qualitest Pharmaceuticals), Tylenol Cold Multi-Symptom Daytime (McNeil Consumer) etc.

m. Multiple Compressed Tablets/ Multi-compressed Tablets

Multiple compressed tablets, also called multi-compressed tablets are tablets that are composed of two or more layers. These tablets are prepared by subjecting the fill material to more than one compression cycle.

The result may be a multiple-layer tablet or a tablet within a tablet, the inner tablet being the core and the outer portion being the shell. 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 pharmaceutical ingredients.

Multiple compressed tablets can also be used when there is a need to mask the bitter taste of a drug substance or where the drug substance in question is irritant to the stomach. There are three subclasses of multiple compressed tablets and they include compression coated tablets, layered tablets and inlay tablets.

i. Compression Coated Tablets

Compression coated tablets also referred to as dry-coated tablets or press-coated tablets, are tablets with two parts; internal core and surrounding coat. These tablets are prepared by feeding previously compressed tablets into a special tablet press (e.g., Manesty Drycota) and compressing another granulation layer around a preformed tablet core.

Compression coated tablets have all the advantages of compressed tablets (i.e., slotting, monogramming, speed of disintegration) while retaining the attributes of sugarcoated tablets in masking the taste of the drug substance in the core tablets.

These tablets can also be used to separate incompatible drug substances (one in the core and the other in the coat); in addition, they can provide a means of giving an enteric coating to the core tablets.

ii. Layered Tablets

They are tablets composed of two or more layers of ingredients. Layered tablets are prepared by compressing additional tablet granulation on a previously compressed granulation to form two-layered or three-layered tablets, depending on the number of separate fills. Each layer may contain a different medicinal agent, separated for reasons of physical or chemical incompatibility, staged drug release, or simply the unique appearance of the layered tablet.

Unlike conventional tablets where we have a single piece of substance moulded to shape, layered tablets have the appearance of a sandwich because the edges of each layer are exposed.

iii. Inlay Tablets

Inlay tablets, popularly known as dot, or bull’s-eye tablets are variation of compressed tablets with a partially surrounded core. Instead of the tablet core being completely surrounded by the coating, its top surface is completely exposed.

Inlay tablets are prepared by feeding previously compressed tablets into a prefilled die cavity of Stokes, Colton, or Kilian machines. When compressed, some of the coating material is displaced to form the sides.  With a yellow core and a white coating, Inlay tablets resemble a fried egg.

Inlay tablets can be useful in sustained-release preparations to reduce the size and weight of the tablet. A typical example is a European preparation containing 25 mg of hydrochlorothiazide in the bull’s-eye and 600 mg of potassium chloride in the outside portion.

n. Immediate-Release Tablets

Immediate-release tablets are tablets designed to disintegrate and release their medication with no special rate-controlling features, such as special coatings and other techniques. This is the most common type of tablet and examples include, chewable, effervescent, sublingual and buccal tablets.

o. Rapid-release Tablets

Rapid-release tablets, also called rapidly dissolving tablets, rapidly disintegrating tablets, orally-dispersible tablets, quick disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast-dissolving tablets, rapid-dissolving tablets, or porous tablets are characterized by disintegrating or dissolving in the mouth within 1 minute, some within 10 seconds, leaving an easy-to-swallow residue.

Tablets of this type are prepared using very water-soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution without chewing.

Rapid-release tablets offer increased convenience and ease of administration with the potential to improve compliance, especially when swallowing conventional solid oral-dosage forms presents difficulties for the patient.

Notwithstanding these advantages, there are a number of disadvantages and difficulties associated with formulating rapid-release tablets, including drug loading, taste masking, friability, manufacturing costs, and stability of the product.

Examples of rapid-release tablets include Clarinex Reditabs [desloratadine], Schering.

p. Extended-Release Tablets

Extended-release tablets sometimes called controlled-release tablets, prolonged-release, delayed release or sustained release tablets are tablets designed to release their medication in a predetermined manner over a prolonged period of time. These tablet types are categorized into

• Those that respond to some physiological condition to release the drug, such as enteric coatings;
• Those that release the drug in a relatively steady, controlled manner; and
• Those that combine combinations of mechanisms to release pulses of drug such as repeat action tablets.

A typical example of this tablet type is Divalproex-Sodium-Extended-Release-Tablets.

q. Vaginal Tablets/ Vaginal Inserts

Vaginal tablets are uncoated, bullet-shaped, or ovoid tablets designed for vaginal administration. They are prepared by compression and are shaped to fit tightly on plastic inserter devices that accompany the product.

Following insertion, retention and slow dissolution of the tablet occur, releasing the medicaments to provide the local pharmacological effect (e.g. for the treatment of bacterial or fungal infection).

Vaginal tablets may also be used to provide systemic absorption of therapeutic agents. Examples include Gyno-Tiocosid (Neimeth), Gynesatum- Clotrimazole vaginal Tablet (Chazmax Pharmaceutical Industries Limited), Nystamark-Nystatin Vaginal Tablet (Mark Pharmaceuticals) etc.

r. Implantation Tablets/ Implants

These are long-acting sterile tablets designed to provide continuous release of drugs, often over a period of months or a year. They are placed subcutaneously for systemic or local delivery.

Implants are mainly used for the administration of hormones such as testosterone steroids for contraception. They usually contain rate-controlling excipients in addition to the active ingredient(s).

Several types of implants are available including pellets, resorbable microparticles, polymer implants, in situ–forming gel/solid implants, metal/plastic implants, and drug-eluting stents.

Examples of implantation tablets include Implanon – etonogestrel (Organon), Disulfiram Tablet for Implantation etc.

Tablet Excipients/ Ingredients

In tablet formulation, many materials are usually combined at various quantities to produce a tablet that is of good standard. These materials serve different and specialized functions in the tablet. The type and quantity of each raw material used is dependent on the intended tablet type and formulation technique. Tablet Excipients include:

• Binders /granulating fluid –e.g., include acacia gum, tragacanth, corn starch, methylcellulose, gelatin, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone and sugars, such as sucrose, glucose, dextrose, molasses, and lactose etc.
• Bulking agents/ diluents/fillers –e. g., anhydrous lactose, spray dry lactose, microcrystalline cellulose, corn starch, dicalcium phosphate, calcium sulfate, lactose, cellulose, kaolin, mannitol, sodium chloride, etc.
• Disintegrating agents – e.g., starch, clays, celluloses, algins, gums, and cross-linked polymers (croscarmellose, crospovidone, and sodium starch glycolate) etc.
• Lubricants –e. g., metallic stearate (0.1-0.2 % w/w) e.g., magnesium stearate, calcium stearate, stearic acid (0.25-1 %), hydrogenated vegetable oil, corn starch, boric acids, sodium chloride, sodium lauryl sulphate etc.
• Glidants – e.g., colloidal silicon dioxide Cab-o-sil (Cabot), Talc (asbestos-free) etc.
• Colouring agents/ Colourants – e.g., FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, D&C Green No. 5, D&C Red No. 6, D&C Red No. 21. D&C Red No. 22, D&C Red No. 27 etc.
• Flavoring agents/ Flavorants – e.g., Aspartame (Pfzer)
• Adsorbent – e.g., silicon dioxide, magnesium oxide, starch, magnesium silicate etc.

How Tablets are Manufactured

Tablets are commonly manufactured by one of the following manufacturing processes:

Wet granulation

1. Milling of drugs and excipients.
2. Mixing of drugs and excipients (excluding the lubricant).
3. Preparation of binder dispersion.
4. Mixing of binder solution with powder to form a coarse mass.
5. Coarse sieving
6. Drying of moist granules.
7. Sieving of the dried granules and mixing with disintegrant and lubricant.
8. Compression into tablets.

Dry granulation (slugging or roller compaction/ chilsonisation)

1. Milling of drugs and excipients.
2. Mixing of milled powders.
3. Compression of mixed powders into slugs (big tablets).
4. Milling and sieving of the slugs.
5. Mixing with disintegrant and lubricant.
6. Compression into tablets

Direct compression

1. Milling of drugs and excipients.
2. Mixing of powders, disintegrant and lubricant.
3. Compression into tablet

Advantages of Tablets in the Pharmaceutical industry

• Tablets are elegant in appearance and convenient to use.
• They are superior to other dosage forms with respect to chemical, physical and microbiological stability.
• Tablets provide stable and an accurately measured dosage of drug substance to patients.
• Tablets can be formulated to protect unstable drug substances or disguise unpalatable excipients.
• Tablets are generally inexpensive to manufacture.
• It is easier to mask the unpleasant taste of some APIs in tablets thus improving patient acceptability.
• Tablets may be formulated to contain two or more drug substances (even if they are physically or chemically incompatible), thus reducing multiple tablet use.
• Tablets may be easily manufactured to show product identification using coloured coatings, embossed markings, and printing.
• Tablets may be designed to release their active substance at a particular site within the gastrointestinal tract to reduce side effects, promote absorption at that site or provide a local effect (e.g. ulcerative colitis).
• With the exception of proteins which are denatured in the gastrointestinal tract, all classes of therapeutic agents may be administered orally in the form of tablets

Disadvantages of Tablets

• The manufacture of tablets requires a series of unit operations (weighing, milling, drying, mixing etc.) thus there is an increased level of product loss at each stage in the formulation process.
• The absorption of medicament from tablets is dependent on physiological factors, such as gastric resident/emptying time, and thus, vary from one .patient to another.
• The compression properties of certain drug substance are poor and may present problems in their subsequent formulation and manufacture as tablets.

Conclusion

Tablets remain popular as a dosage form, due to the various advantages afforded both to the manufacturer and to the patient. Although the basic mechanical approach for most tablet manufacture has remained the same, efforts are continuously made to understand more clearly the physical characteristics of powder compaction and the factors affecting the availability of the drug substance from the dosage form after oral administration.

NALINIKANTA SWAIN

FORMULATION RESEARCH SCIENTIST

www.nalinikantarnd.blogspot.com