Pharmaceutical Tablets

Tablets are solid dosage forms of medication prepared by compressing or molding. Since the latter part of the 19^th century up to the present time they are the most popular of all kinds of medicinal preparation intended for oral use.

Advantages of Tablets:

1. Accuracy and compactness of dosage
2. Simplicity and economy in manufacturing
3. Convenience in dispensing and shipping
4. Simple to identify
5. Blandness of taste to make it easily to swallow
6. Available in special-release forms
7. Most stable in all dosage forms
8. Best suited to large-scale production
9. Essential tamper-proof.

Disadvantages:

1. Some drugs are incompatible to compress into tablets.
2. Some drugs are hardly to reach the adequate bioavailability.
3. Undesirable tastes and odor of some drugs cannot be masked.

Tablet Characteristics:

The different specifications by which compressed tablets are characterized includes the diameter size, shape, thickness, weight, hardness and disintegration time. The diameter and shape depend on the die and the punches used for compression. In general, tablets are discoid in shape, however, they may be oval, oblong, round, cylindrical or triangular. The upper and lower surfaces may be flat, round, concave or convex to various degrees. The concave punches maybe shallow, standard and deep cut.

Tablet Types and Classes

1. Tablet for oral ingestion
   
   
   a. Compressed Tablets are tablets made from crystalline or granular materials, alone or in combination with binders, disintegrants, lubricants and fillers. They are formed by compression and do not contain special coating.
   b. Multiple compressed tablets are compressed tablets made by more than one compression cycle.

• Layered tablets are tablets prepared by compressing additional tablet granulation on a previously compressed tablet. This operation may be repeated a number of times to produce a multi-layered tablet.

• Compression-coated tablets are tablets prepared by feeding a previously compressed tablet into a special tablet machine and compressing another layer around this performed tablet. With this method a compressed tablet in which compatible ingredients may be kept in separate layers. It has all the advantages of the compressed tablet, such as: - sletting, monogramming, speed of disintegration, etc. while retaining the attributes of the sugar-coated tablets in masking the taste of medication in the internal layers.

c. Repeat-action tablets are layered tablets in which the outer layer gives an initial dose, quickly disintegrate in the stomach. The inner layer contains of components that are insoluble in gastric solution but soluble in intestinal solution.


d. Delayed-action and enteric-coated tablets are tablet coatings that resist solution in gastric fluid but disintegrate and release their medication in the intestines. Among the agents used to enteric-coat tablets are fats, fatty acids, waxes, shellac and cellulose acetate phthalate.


e. Sugar-coated tablets are coating that cover up medicinal possessing objectionable tastes and odors, and protect sensitive medicinals subject to deterioration. Sugar-coated may be coated with a colored or an uncolored sugar. The process includes seal coating (waterproofing), subcoating, syrup coating (for smoothing and coloring), and polishing. Sugar-coated tablets may be 50% larger and heavier than the usual tablet.

f. Chocolate-coated tablets originally chocolate was used as a coloring material, but at present the iron oxide standardized as to color are available and largely replaced chocolate for this purpose.

g. Film-coated tablets are thin layer or film of a water-soluble imparts the same general characteristics as sugar-coated tablets with the added advantage of greatly reduced time required for the coating operation. A number of polymeric substances with film-coating properties are used for this purpose.

h. Air suspension-coated tablets are placed into a vertical cylinder that supported by a column of air and enters from the base of the cylinder. As the coating solution enters the system, it is rapidly applied to the suspended rotating solids. Rounding coats can be applied in less than 1 hour with the assistance of warm air blasts released in the chamber.

j. Chewable tablets are tablets that disintegrate smoothly and quickly when chewed or allowed to dissolve in the oral cavity, giving a creamy base from specially colored and flavored mannitol. This formulation is terrific for children that commonly applied to multivitamin tablets.

2. Tablets used in the oral cavity
   
   
   a. Buccal or sublingual tablets are small, flat, oval tablets intended to be inserted in the buccal pouch, or beneath the tongue, where the active ingredient may be directly absorbed through the mucosa.
   
   
   b. Troches, lozenges, and dental cones dissolve slowly in the mouth and provide primarily local effects.
   
   
3. Tablets used to prepare solutions

a. Effervescent tablets are prepared by compressing granular effervescent salts or other materials such as citric acid, tartaric acid, sodium bicarbonate, that have the capacity to release carbon dioxide gas when in contact with water.

b. Dispensing tablets those tablets are not to be dispensed as such as they contain very large and sometimes lethal doses of the potent drug. They provide a convenient quantity of a potent drug that can be incorporated readily into powders, liquids, and other preparations at the dispensing counter.

c. Hypodermic tablets are tablets made in a tablet triturate mold and are intended for use in making hypodermic preparation for injection. They are made with absolute cleanliness as they usually used to prepare parenteral solution extemporaneously, so they must be completely and rapidly soluble in the vehicle.

Compressed Tablets

Medicinal substances either in crystalline or powdered form intended to be made in dosage form with pressure using available equipment should possess a number of physical characteristics, such as:

• Ability to flow freely – to ensure a uniform fill in the die cavity and to allow continuous movement of the granulation from the sources or food hopper.
• Cohesiveness – ability to hold together the materials thus preventing tablets from crumbling and falling apart on handling.
• Lubrication – to minimize friction and to favor the removal of the compressed tablets from the punch faces. Since these properties are not commonly found in the ingredients methods should be adopted to impart these desirable characteristics to the materials.

Tablet Ingredients:

1. Active or therapeutic ingredients
2. Additives or excipients are inert materials which can be classified according to their function into:

• Those which help to impart satisfactory compression characteristics like diluents, binders and lubricants.
• Those that help to give additional desirable physical characteristics to the finished tablet like disintegrants, colors and flavors.

Tablet Excipients:

1. Diluents – These are inert substances added to increase the bulk in order to produce a practical size for compression. Dicalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch and powdered sugar are some of the common diluents. Mannitol has a pleasant taste, chemically stable and is not hygroscopic hence it is usually employed as a diluent for chewable tablets. Most tablet formulators use only one or two diluents. Care should be observed regarding incompatibilities between active ingredients and diluents. Calcium salts interfere with the absorption of tetracycline from the gastrointestinal tract. Amino bases with lactose and alkaline lubricant will produce discolored tablets on aging.
   
   
2. Binders or Granulators – These are substances added to the powdered material to impart a cohesiveness to the formula which ensures the tablet to remain intact after compression. Binders also improve the free-flowing qualities by the formulation of granules of desired hardness and size. The most common binders are starch, gelatin, and sugars like sucrose, molasses and lactose. Natural and synthetic gums which have been used include acacia, sodium alginate, extract of Irish mess, carboxymethylcellulose, methylcelluloses, polyvinylpyrrolidone, veegum, and larch arabogalactan. Polyethylene glycol, ethylcellulose, waxes, water and alcohol may also be considered as binders.
   
   
3. Lubricants – These improves the rate of flow of the tablet granulation, prevent adhesion of the tablet material to the surface of the dies and punches, reduce interparticle friction, and facilitate the ejection of the tablets from the die cavity. Examples of them are talc, calcium and magnesium stearate.
   
   
4. Glidants – They improve the flow properties of the granules in the food hopper. Examples are talc, starch, lycopedium, calcium and magnesium stearate, boric acid, sugar and sodium chloride.
   
   
5. Antiadhesives or antisticking agents – Prevent adhesion of the tablet to dies and punches during compression. Examples are paraffin, stearic acid, cocoa butter and soaps.
   
   
6. Disintegrants – These are substances or mixture of substances, added to a tablet to hasten the disintegration or breaking up after the tablet is administered. Release of the active ingredient should be accomplished as efficiently as possible to allow rapid dissolution. Examples are veegum, methylcellulose, agar, bentonite, cellusloe, wood products, natural sponge, cation-exchange resins, alginic acid, guar gum, citrus pulp and carboxymethlycellulose, surfactants, like sodium lauryl sulfate.
   
   
7. Coloring Agents – The use of color in compressed tablets is for several reasons. It helps the manufacturer control the product during its preparation, it serves to identify the product and to give and aesthetic appearance to the tablet.
   
   
8. Flavoring Agents – For compressed tablets, the addition of flavoring agents is not a necessity. But for chewable tablets and lozenges, it is often required. The flavors may be sprayed as an alcoholic solution into the dry granules before compression or “dry flavors” may be mixed with the other tablet constituents.

Processing Problems

1. Capping is the partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet. A remedy for capping is to dampen the mixture slightly with water alcohol, a mixture of alcohol and water or glucose solution prior to compressing, as long as there is no incompatibility involved.
   
   
2. Lamination is separation of a tablet into two or more distinct layers. Both capping and lamination are problems usually result from air entrapment during processing.
   
   
3. Picking is removal of a tablet's surface material by a punch. 
    
4. Sticking is adhesion of a tablet material to a die wall. These problems may result from excessive moisture or substances with low melting temperatures in the formulation.
   
   
5. Mottling is an unequal color distribution on a tablet, with light or dark areas standing out on an otherwise uniform surface. This may result from use of a drug with a color different from that of the tablet excipients or from a drug with colored degradation products. Colorants may solve the problem but may also create other problems.

Quality Control

A. Tablet Hardness: Storage, transportation and handling requires tablets that can resist chipping, abrasion or breakage. A usual rule of thumb test is to break the tablet between the second and third fingers using the thumb as the fulcrum. It is of proper hardness if it breaks with a sharp snap. When dropped on the floor, however, it should not break.

To determine quantitatively the degree of hardness, an instrument, the Mensanto or Stokes hardness tester is tablet when the force generated by a coil spring is applied diametrically to the tablet. Another method of testing hardness is by the use of the Roche friabilator. A number of tablets are weighed and placed in a tumbling apparatus where they are exposed to rolling and repeated shocks resulting form free falls within the apparatus. After a given number of rotations the tablets are weighed. The loss in weight indicates the ability of the tablets to withstand abrasion in packaging, handling and shipping.

B. Tablet Thickness: The density of the granulation and the pressure applied to the tablets may change the thickness of the tablet without causing a change in weight. This should not be tolerated to maintain identical appearance of the tablet and to ensure that every production lot will be usable with a selected packaging components. Thicker tablets may no longer be accommodated in the volume of a given size bottle. Thickness is measured by a caliper like the Ames thickness gauge which gives reading in millimeters. Depending on the size of the tablet, a plus or minus 5% may be allowed.

C. Tablet Weight: The weight of the compressed tablet, determined by the volumetric fill of the die cavity, is the quantity of the granulation which contains the labeled amount of the therapeutic ingredients. After the tablet machine is in operation, the weight of the tablets are checked routinely to ensure that the tablets have the proper weights. This is done by weighing 20 capsules individually and the average weight is calculated. The weight of not more than two of the tablets should not differ from the average weight by more than the percentage, no tablet differ by more than double that percentage.

D. Tablet Disintegration: The in vitro disintegration test uses not necessarily bear a relationship to the in vivo action of a solid dosage form. Regardless of the lack of significance as to the tablets in vivo action, the test provides a means of control in assuring that a given tablet formula is the same as regards disintegration from the product batch to another.

Methods of Preparation

A. Wet – Granulation Method

This is the most widely used and most general method of tablet preparation because the granules formed usually meet the physical requirements for the compression of food tablets. However, this method presents certain disadvantages: the number of separate steps involved and the time and labor needed to carry out the procedure especially on large scale.

The steps in the wet method are:

1. Weighing
2. Mixing
3. Granulation
4. Screening the damp mass
5. Drying
6. Dry screening
7. Lubrication
8. Compression

B. Dry – Granulation Method

Dry granulation, precompression, or the double-compression method is employed when the tablet ingredients are affected by moisture, elevated temperature due to drying, and when the ingredients have sufficient inherent binding or cohesive properties. The is shorter.

The steps involved are:

1. Weighing
2. Mixing
3. Slugging
4. Dry screening
5. Lubrication
6. Compression

The active ingredient, diluent (if necessary) and part of the lubricant are blended. The active ingredient or the diluent must have cohesive properties. Since powdered material contains considerable amount of air which when expelled under pressure forms a fairly dense tablet, more time should be allowed for this air to escape to produce a better tablet or slug.