Pharmaceutics PDF Notes: Dosage Forms

5.1 Introduction

A dosage form may be defined as a combination of medicament and non-medicament components with mixture of suitable excipients.

5.2 TABLET

Tablet may be defined as a solid unit dosage form, containing one or two drug with or without non-drug component called excipients or additives. Tablets are prepared either by compression or molding method. They may be circular, flat or biconvex in shape.

Advantages:

The tablets are easy to be administered.
These are more stable dosage forms.
Bitter and nauseous substances can be given easily in tablet form after giving a suitable coating to the tablets.
Tablets are easiest and the cheapest as regard packing and transport.
These are an economical dosage form.

Disadvantages:

The onset of action is slow compare to liquid dosage form.
The bioavailability is less compared to liquids and parenterals.
The drugs which get decomposed by gastric juices and enzymes cannot be formulated as tablets.
The drugs which are sensitive to light and moisture requires coating.

5.2.1 Classification

Tablets are classified according to their route of administration or function. The following are the four main classification groups:

I) Tablets ingested orally:
Compressed tablets
Enteric coated tablets
Sugar coated tablets
Film coated tablets
Chewable tablets

II) Tablets used in the oral cavity:
Buccaltablets
Sublingual tablets
Lozenges tablets
Dental cones

III) Tablets administered by other routes:

Implantationtablets
Vaginaltablets

IV) Tablets used to prepare solution:
Effervescenttablets
Tablet triturates

5.2.2 Tablet Additives / Excipients / Adjuvants

In addition to the active medicament, each tablet contains some additives or excipients.

1) Diluents: If the medicament is in small quantity, it is added to increase the bulk in order to make the tablet a suitable size for compression.

Ex: Lactose, Dicalcium phosphate, calcium sulphate.

2) Binders or Granulators: It gives the cohesiveness to the powdered materials so that the powder can be converted into granules. Binders are used in 10% concentration.

Ex: Acacia, starch, starch mucilage.

3) Lubricants: Substances which improve the rate of flow of granules prevent to the surface of the dies and punches and facilities the ejection of tablets from the die cavity used in 1% concentration.Ex: Talc, magnesium stearate, calcium stearate.

4) Glidant: It improves the flow properties granules from the hopper. It is used in 1% concentration.Ex: magnesium stearate, calcium stearate.

5) Disintegrators: A disintegrator is a substance or a mixture of substances included in tablet formulation to facilitate the disintegration of the tablet after administration. It is used in 5-15% concentration. Ex: Starch, cellulose, gums.

6) Coloring agents: It gives elegant appearance to the tablet.

Ex: Amaranth, tartrazine, sunset yellow.

7) Flavoring agents: It gives good flavour to thetablet. They are mixed with dry granules by spraying the flavours on the granules before compression. 0.5% volatile oils are used. Ex. Peppermints

8) Sweetening agent: It masks the bitter taste of the medicaments.

Ex: Dextrose, lactose, mannitol, saccharin.

5.2.3 Methods of preparation of Tablet/Processing of Tablet

Tablets are prepared by three methods:

1) Wet granulation method.

2) Dry granulation method.

3) Direct compression method.

A) Wet granulation method:
Weighing and mixing: The required quantities of the ingredients are weighed. The active medicament, diluents, coloring agent and disintegrating agent are mixed well and passed through a sieve to remove lumps.
Granulation: The powder mixture is wetted with liquid binding agent and mixed well until a coherent mass is formed.
Screening the damp mass: The wet mass is passed through a sieve by hand.
Drying: The moist granules are placed on large sheets of paper on wire trays. The trays are placed in hot air oven and the granules are dried at 60⁰C.
Dry screening: After drying, the dried granules are once again passed through a smaller mesh screen (16 or 20 mesh). During this screening the granules size will be more uniform.
Lubrication and compression: After dry screening the granules are mixed with lubricating agent. If necessary, flavoring agent and sweetening agent can also be mixed with dry granules before compression finally the granules are compressed.
B) Dry granulation method: This method is also known as slugging method or double compression method or pre compression method. This method is suitable, when the ingredients are sensitive to moisture and heat and also when the ingredients have cohesive or binding properties.
Weighing and mixing: The active medicament, diluents, disintegrating agent and part of the lubricating agent are weighed, mixed and passed through a sieve to remove lumps, binding agent is not necessary.
Slugging: The powder mixture is then compressed into large tablets. These large tablets are known as slugs.
Dry screening:Thecompressed slugs are then broken into suitable sized granules in an oscillating granulator machine and then passed through the sieve to obtain uniform sized granules. Drying by heat is not necessary.
Lubrication and compression: After dry screening, the granules are mixed with the remaining lubricating agent and compressed into tablets.

Ex: Acetyl salicylic acid, thiamine hydrochloride, ascorbic acid, magnesium hydroxide etc.

C) Direct compression method: There are certain medicaments which are available in crystalline form or in the form of granules having its own binding property. Such medicaments are passed through sieve no. 20 or any other specified sieve and then mixed with any additional excipients.

Ex: Aspirin, sodium bromide, potassium chlorate and dried yeast etc.

5.2.4 Quality control test for the tablets

Testing tablets for quality should be considered and completed throughout the manufacturing process; this begins with testing raw materials and continues with in-process testing, along with final release testing. Monitoring manufacturing processes will ensure that consumers receive safe products.

This includes following tests:-

Shape and appearance of tablet
Weight variation
Tablet thickness
Content uniformity test
Friability test
Hardness test
Disintegration test
Dissolution test

Shape and appearance of tablet:The shape and appearance of tabletalways depends on dies and punches during compression any default in the thickness, shape and diameter should be controlled. Thickness and diameter was determined by using slide caliper.
Weight variation

20 tablets are weighed individually and the average weight is calculated. The weight of 2 tablet should not be morethan and also not deviate from the average weight percentage given in the standard table.

Standard weight variation table:

Average weight of tablets	Percentage deviation
120mg or less	+10
More than 120mg and up to 300mg	+7.5
More than 300mg	+5

Tablet thickness: If the tablets are thicker than the specified size, they cause problems during packing, therefore thickness or diameter of the tablets is determined with a screw gauge. 5% deviation may be allowed depending on the size of the tablet.
Content uniformity test: This test is performed to ensure that every tablet must contain the stated amount of medicaments within the prescribed limits given in the pharmacopoeia.
Friability test: Friability test tells us how much mechanical stress tablets are able to withstand during their manufacturing, distribution and handling by the customer.
Hardness test: Tablets require certain amount of strength or hardness to withstand mechanical shocks of handling in manufacture, packaging and transportation. If the tablets are too hard, they may not disintegrate within the prescribed time. If it is too soft, they will not withstand mechanical shocks of handling in manufacture, packaging and transportation.

Disintegration test: Disintegrator of a tablet means to break the tablet into smaller particles after swallowing.The test is carried out using disintegration tester. A basket supporting with 6 cylindrical glass tubes with 6 holes having the diameter as the tubes. The Tubes are fitted with a motor in such a way that they move up and down motion. The bottoms of the tubes are covered with 10mesh screen. Six tablets are placed in the tubes. The motor is switched on. The tubes are moved up and down motion into the distilled water. The temperature of the distilled water is maintained at 37⁰C. If all the particles from the tablets pass through the wire mesh within 30 min, it indicates that the tablet passes the test. For coated tablet is 1hr.

Dissolution test:This test is done for measuring the amount of time required for a given percentage of the drug substances in a tablet to go into solution under specified condition in vitro. It consists of a stainless steel basket. The bottom of the basket is covered with 40mesh screen. 1 tablet is taken in the basket and it is immersed in the dissolution fluid which is maintained at the temperature of 37⁰C. The basket is allowed to rotate at specified speed. The samples of the dissolution fluid are removed at specified intervals of time and analyzed the drug content.

The volume of dissolution fluid is maintained constant by adding a volume equal to that removed for analysis. The test is repeated with another five tablets. If 1 or 2 tablets fail to meet the requirements, the test is repeated on 6 additional tablets, not less than 10 out of 12 tablets must meet the requirements.

5.2.5

COATED TABLET

Coated tablets are defined as “tablets covered with one or more layers of mixture of various substances such as: Natural or Synthetic Resins, Gum, Sugar, Waxes, Authorized Colouring Materialand Some Times Flavoring Material etc.

Coating of the tablet was done for the following reason-

To mask the unpleasant taste and odour.
To improve the appearance of the tablets
To prevent the medicaments from atmospheric effects.
To control the site of action of drugs.
To produce the sustained released product.

Types of tablet coating:

Sugar coating
Enteric coating
Film coating
Gelatin coated tablet
Compressed coating Tablet

1) Sugar Coating: Sugar coating is usually soluble in water, causing it to dissolve quickly when exposed to any liquid medium, for example, gastrointestinal fluid. The major advantage of sugar coating is that it eliminates unpleasant or bitter taste, odour, and makes it easier to swallow.

2) Enteric coating: Enteric coating tablets have a cellulose coating or other materials that prevent their degradation in stomach and make them usable in the intestine. Enteric coating is a process that is particularly prepared to work the tablet in the alkaline pH of the intestine rather than the acidic pH of the stomach.

3) Film coating: Enteric coating tablets have a cellulose coating or other materials that prevent their degradation in stomach and make them usable in the intestine. Enteric coating is a process that is particularly prepared to work the tablet in the alkaline pH of the intestine rather than the acidic pH of the stomach.

4) Gelatin coated tablet: Gelatin coating tablets are made by spraying less bloom solution of gelatin and water onto pre-coated tablets, the gelatin coating provides a lower coefficient of friction and consequently increased slippery and swallowing ability for tablets without thickness and stickiness. It is suitable for both wet granulation and direct compression. The pharmaceutical manufacturers also broadly used the empty gelatin capsules to encapsulate dosage forms of various drugs.

5) Compression coating:Compression coating is of the significant dry coating method that does not need either heat or solvent to perform the coating. It is used to protect the active drug component (API) from the environment and is also used to release modified medicine. The important area where compression coating is widely used is site-specific drug delivery, especially colon-specific drug delivery. Compression coating is a system in which the whole surface of an inner core is surrounded by a coat. It is widely used for particularly colon-specific drug delivery and site-specific drug delivery.

5.2.6

UNCOATED TABLET

The uncoated tablet is a single layer or multi-layer of formulation that contains the drugs or medicines and excipients simultaneously without any coating. In general, it is a single compression of granules or multi-layer tablets consisting of parallel layers prepared by compression of granules of various compositions. These types of pills do not require additional processing after compression. The majority of uncoated tablets are made in such a way any substances added are not intended expressly to alter the release rate or dissolution rate of their active ingredients. Soluble tablets, dispersible tablets, and effervescent tablets are some types of uncoated tablets.

5.2.7

VARIOUS MODIFIED TABLET

Sustained release Tablet

Sustained release dosage form is defined as well characterized and reproducible dosage form, which is designed to control drug release profile at a specified rate to achieve desired drug concentration either in blood plasma or at target site.This system will provide actual therapeutic control that would be temporal (time related), spatial (site related) or both

Advantages of sustained drug delivery system:

Reduced see-saw fluctuations.
Total amount of dose decreases.
Improved patient compliance.
Increased safety of drugs [15-19].

Disadvantages of sustained drug delivery system:

Chances of dose dumping.
Dose retrieval is difficult.
High cost of formulation.
Need for additional patient education.
Reduced potential for accurate dose adjustment

Extended release tablet

The drug delivery system that allows at least two folds reduction in dosage frequency as compared to that drug presented as an immediate release system. They also differ from immediate release tablets which release content within few minutes of ingestion ER tablets slowly release drug into the body over a period of time, usually 12 hours or 24 hours and are only taken once or twice a day. They are specially designed to release a pre-designated amount of medication throughout the day.

Advantages

Less frequent dosing
Fewer side effects
Fewer fluctuations in blood levels,
Complete absorption
Potential to improved patient compliance and convenience
Increased stability,improved bioavailability, providing special effects, etc.
The drug release rates are affected by presence of food in GIT

Disadvantages

Slower onset of action
Comparatively high cost
The size of ER tablet may cause difficulties in ingestion or transit through gut.
Sometimes the target tissue is exposed to constant amount of drugover extended period resulting in drug tolerance
Air or moisture can change the effectiveness of ER tablets, so it is important to store them in sealed bottles and in a dry place.

Fast Dissolving Tablets

Fast dissolving tablets (FDT) are solid dosage forms designed to dissolve in saliva remarkably faster, within a few seconds (usually less than 60 sec), and those are real fast dissolving tablets.
FDTS disintegrate rapidly in saliva without the need to take water and are of commonly used for the pediatric and geriatric patients who have difficulties such as fear of choking while swallowing them with water or have difficulties in chewing them; sometimes very elderly patients of depression may not be able to swallow conventional tablets.
FDTS can also be known as orally disintegrating or dispersible tablets (ODTS), mouth melting tablets (MMTs) or mouth dissolving tablets (MDTs), immediate release (IR) tablets.
Mouth dissolving tablets are formulated by use of super disintegrants like Croscarmellose sodium, sodium starch glycolate and crospovidone or by maximizing pore structure of the Tablets by freeze drying and vacuum drying.

Advantage:-

No need of water to swallow the Tablet
Easy administration to pediatric, elderly and mentally disabled patients.
Faster dissolution and absorption of the drug offering rapid onset action
Increased bioavailability
Reduce first pass metabolism

Disadvantage:-

FDTS being highly porous, soft molded metrics or compressed with low compressional pressure are friable and brittle which make them difficult to handle
Several of the FDT are hygroscopic and thus cannot maintain its physical integrity under normal humidity condition and thus requires specialized package.
Dryness of the mouth due to decreased saliva production may hamper dissolution, rate of absorption from the saliva solution and overall bioavailability.

Multilayered Tablet

Multilayer tablet consists of layers of drug with different release rate, having ability to prevent drug-excipient incompatibility. It provides multiple release kinetics profile in single delivery system of one or more drugs. In this immediate release and then sustained release of drug is designed as control system. Immediate release layer is designed with disintegrating monolithic matrix in order to achieve initial peak and sustained release layer is designed with erodible monolithic matrix to deliver the drug as later part to maintain the drug plasma concentration. The mechanism of drug release from multilayer tablets.

Advantages of drugs

Cost is lower compared to all other oral dosage form.
Greatest chemical and microbial stability over all oral dosage form.
Unpleasant odour and bitter taste can be masked by coating technique.
They are unit dosage form and offer the greatest capabilities of all oral dosage form for the greatest dose precision and the least content variability.
Easy to swallowing with least tendency for hang-up.
The tablet can be easily used for combination therapy.
In case of drugs having a low half-life, each of the two layers of the tablet respectively content a loading dose and maintenance dose of the same and thus increase the bioavailability of the drug.
Improved patient compliance.

Disadvantage of Multilayered Tablet:

Some drugs resist compression into dense compacts, owing to amorphous nature, low density character.
Bitter testing drugs, drugs with an objection able odour or drugs that are sensitive to oxygen may require encapsulation or coating.
Difficult to swallow in case of children and unconscious patients.
Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT may be difficult to formulate or manufacture as a tablet that will still provide adequate or full drug bioavailability.
Lack of sufficient bonding and adhesion at the interface between the adjacent compacted layers which is often the result of an interfacial crack and layer separation.
Other challenges during development include establishing the order of layer sequence layers, first layer tamping force, and cross contamination between layers.
The physician has a less flexibility on adjusting the dose regimens.