DRUG DOSAGE FORMS & DELIVERY SYSTEMS


Molded Tablets

  • These are usually made from moist material using triturate mold that gives them the shape of cut sections of a cylinder.
  • Prepared from mixtures of medicinal substances and a diluent usually consisting of lactose and powdered sucrose in varying proportions.
  • The powders are dampened with solutions containing high percentage of alcohol. These are pressed into molds, removed, and allowed to dry
 
A. Dispensing Tablets
  • These tablets provide a convenient quantity of potent drug that can be incorporated readily into powders and liquids.
  • These tablets are supplied primarily as a convenience for extemporaneous compounding and should never be dispensed as a dosage form.
  • A tablet prepared by molding or by compression; used by the dispensing pharmacist to obtain certain potent substances in a convenient form for accurate compounding.
  • Formerly used to prepare bulk solutions of germicidal chemicals, bichloride of mercury. Not intended for internal use
B. Hypodermic Tablets
  • These are soft, readily soluble tablets and were originally used for the preparation of solutions to be injected.

Compressed Tablets

These tablets are formed by the process of pressing powdered, crystalline or granular materials, alone or in combination with excipients to form a compact adherent mass of predetermined shape.

Factors Influencing the Variety of Compressed Tablets
I. The manner of use of the tablet, such as:
  • Chewable
  • Buccal
  • Sublingual
  • Implantation
  • Vaginal
  • Special oral tablets (multiple layered and coated)
II. Specific mode of action
  • Effervescent
  • Soluble
  • Sustained release
 
I. The manner of use of the tablet
Chewable Tablets
  • These are tablets recommended to “speed up” disintegration by breaking up or mastication in the mouth.
Buccal Tablets
  • These are small, flat, oval tablets intended for buccal administration by inserting into the buccal pouch to dissolve or erode slowly. Example, Progesterone tablets.
  • NOTE: Both buccal and sublingual tablets are applicable for those drugs that are better absorbed through the oral mucosa
Sublingual Tablets
  • Examples are nitroglycerin and isoproterenol hydrochloride.
  • usually a small, flat tablet intended to be inserted beneath the tongue, where the active ingredient is absorbed directly through the oral mucosa; such a tablet (nitroglyerine) dissolves very promptly.
Implantation Tablets or Pellets
  • These are small tablets compressed without excipients.
  • They are rendered sterile, since they are inserted into the body tissues by surgical procedures, where as a result of hardness and slow solubility, are slowly absorbed into the body.
Vaginal Tablets, Tablet Suppositories or Inserts
  • These are specially formulated and shaped tablets, which are inserted into the vaginal canal (very much like vaginal suppositories) using a special inserting device or fingers. It exerts localized effects.

Special Oral Tablets

Multiple Layered Tablets
  • These are tablets prepared by the compression of several different granulations fed into a die in succession, one on top of the other in layers.

Layered Tablets
  • Are prepared by compressing additional granulation on a previously compressed granulation.

Press-coated Tablets
  • Are prepared by feeding previously compressed tablets into special tableting machine and compressing another granulation layer “around” the preformed tablet.

Sugar-coated Tablets
  • Are compressed tablets containing a sugar coating.
  • Such coatings may be colored and are beneficial in covering up drug substances possessing objectionable tastes or odors, and in protecting materials sensitive to oxidation

Film-coated Tablets
  • Are covered with a thin layer film of water-soluble material. A number of polymeric substances with film-forming properties may be used.
  • Advantage: Reduced time period required for the coating operation.

Advantages of Special Oral Tablets:
  • Two or more incompatible drugs may be kept separate by interposing an inert substance between layers.
  • Each layer may have separate color for identity.
  • Accurate control of the delayed/ sustained release action portion of the tablet is possible.

Advantages of Compressed Tablets:
  1. Precision of dosage
  2. Durability of the physical characteristics for extended periods of storage
  3. Stability of chemical and physiological activities of the drug
  4. Convenience of administration
  5. Portability of carriage and transport
  6. Aesthetically appealing

Properties of a Compressed Tablet
  • Ability to withstand the rigors of mechanical treatment involved in the production, packaging, shipment and dispensing.
  • Freedom from defects such as cracks, chipped edges, discoloration, specking and contamination.
  • Reasonable physical and chemical stability during average storage conditions
  • Ability to release the medicament in a reproducible and predictable manner.

Manufacturing of Tablets

The tablet is a vehicle for conveying the medication to the patient and therefore, the formulator should be aware of the limitations of the raw materials and equipment since these affect the bioavailability of the medicament.

Tableting Machine

Basic parts of Tableting Machines

  • Hopper — for storing the granulation material for compression
  • Feed frame/ Feed Shoe — for distributing the granulation material into the die cavities
  • Die Cavities — for controlling the size and shape of the tablets
  • Punches (upper and lower) — for compacting the granulation material within the die cavities.
  • Cams — for guiding the punches

Types of Tableting Machines
  1. Single Punch Press

    This is consist of a hopper, feed shoe, weight adjustment, collar (which when turned clockwise, reduces the fill weight and when turned counter clockwise increases the fill weight), one set of the cavity and punches (upper and lower), discharge chute, cam and an upper adjustment collar (which determines the position of the lower punch at the point of ejection of the finished tablet)

  2. Multi-station Rotary Tablet Machines

    For increase production output, these machines offer great advantages. A head carrying a number of sets of dies and punches revolves continuously, while the tablet granulation runs from the hopper, through a feed frame and into the dies placed in a large steel plate revolving around it.

  3. High Speed Rotary Tablet Machines
    • The rotary tablet machine has gradually evolved into models capable of compressing tablets at high production rates. This has been accompanied by:
    • increasing the number of stations (i.e. sets of punches and dies, in each revolution of the machine head)
    • improvement in “feeding” devices
    • installation of dual compression points
  4. Multi-layer Rotary Tablet Machines

    The rotary tablet machines have been developed into models capable of producing multiple-layered tablets. These machines are able to make one, two or three layered tablets.


Preparation of Tablet Components for Compression
I. Dry Granulation Method

— Also called Pre-compression; Double Compression Method

— This method is applicable to tablet ingredients that are/ have sensitive to moisture

Raw material arrow_forward weighing arrow_forward Screening arrow_forward Mixing arrow_forward Slugging arrow_forward Milling arrow_forward Screening arrow_forward Mixing arrow_forward Compression

A. Direct Compression

  • A few crystalline substance like inorganic salts (NaCl, NaBr and KCl) may be compressed directly (without any excipients), but majority are not easy to tablet.
  • To remedy this problem, the uses of directly compressible vehicles are advised. These are inert substances, which may be compacted with no difficulty, and may do so even when mixed with drugs.
  • Examples are dried lactose, anhydrous lactose, calcium phosphate, mannitol, sorbitol and Avicel.

Raw material arrow_forward Weighing arrow_forward Screening arrow_forward Mixing arrow_forward Compression

B. Granulation by Compression

This method is adopted for tablets components that are sensitive to heat, moisture or both. It is further divided into two methods namely

  1. Slugging by a Tablet Press
    • Also similar to dry granulation method
    • Granulation by slugging is the process of compressing dry powder of tablet formulation with tablet press having die cavity large enough in diameter to fill quickly.
  2. Use of Chilsonator
    • It consists of 2 rollers controlled by hydraulic drums. The tablet materials are fed the hopper to the rollers which contain a spiral impeller to de-aerate the powder.
    • After passing the roller, the compacted mass resembles a thin cake. The aggregates are formed from the “cake” are screened to produce the tablet granulation.
II. Wet Granulation Method

A. Wet Granulation

  • The most widely used method of tablet preparation. Its popularity is due to greater probability that the granulation will meet all the physical requirements for the compression of good tablets.

Disadvantages

  • the number of several steps involved
  • it requires longer processing time
  • labor cost it high

Raw material arrow_forward Weighing arrow_forward Screening arrow_forward Wet massing arrow_forward Sieving/Milling arrow_forward Drying arrow_forward Screening arrow_forward Mixing arrow_forward Compression

Tablet Additives and Components

Additives or Excipients furnish bulk or volume to the tablets and are classified according to their functions as follows:

  1. Diluents
  2. Binders
  3. Disintegrant
  4. Lubricant
  5. Coloring Agent
  6. Flavoring Agent
  7. Adsorbent

1. Diluents

These are substances that make up the major portion of the tablet, usually:

1.a. Lactose USP

Most often used because of the following advantages:

  • it is stable and does not react with most medicinal substances
  • its rapid solubility in water means quick release of the drug substance
  • non-hygroscopic and possess a high melting point, so it is not softened by frictional forces of machine compression

1.b. Starches

  • they are employed as binders and disintegrants
  • Stabilize hygroscopic drugs and protect the tablets of such materials from deterioration.

1.c. Sucrose

  • Advantage: It is sometimes added to provide additional sweetness, but its’ main use is as a binder because of it’s cohesive property.
  • Disadvantage: Oxidizes (turns dark brown), when it comes in contact with acidic and basic substances.

1.d. Mannitol

  • This another sugar used for special situations, due to its high cost. It as sweet and obtained as powder or granules.
  • Mannitol is extensively used for chewable tablets.

1.e. Microcrystalline Cellulose (Avicel)

  • a very expensive tablet diluents

1.f. Hydrolyzed starch with dextrose

  • Its’ concentration is 95 to 96%; it contains 4 to 5% polysaccharides. It is also used as a base for chewable tablets due to sweet taste and pleasant “mouth feel”

Other common diluents

  • Lactose-anhydrous and spray dried lactose
  • Directly compressed starch-Sta Rx 1500
  • Hydrolyzed starch-Emdex and Celutab
  • Dibasic calcium phosphate dehydrate
  • Calcium sulphate dihydrate
  • Sorbitol
  • Sucrose- Sugartab, DiPac, Nutab
  • Dextrose

2. Binders

These Excipients are substances that “glue” powders together, and cause them to form granules. Binders are added in dry form to the powdered medicaments and activated by the addition of water or other solvents to form a slurry or paste.

Examples of raw materials employed as binders are:

  • natural gums (acacia, tragacanth)
  • sugars (sucrose)
  • starch gelatin
  • polyvinyl pyrolidone (PVP) in alcohol
  • cellulose derivatives (ethylcellulose, methylcellulose in chloroform)
  • Gelatin- 10-20% solution
  • Glucose- 50% solution
  • Polyvinylpyrrolidone (PVP)- 2% conc.
  • Starch paste-10-20% solution
  • Sodium alginate
  • Sorbitol

3. Disintegrants

These are substances or agents added to compressed tablets to cause them to “break apart” or disintegrate, when placed in an aqueous medium.

Examples of raw materials employed as disintegrants are:

  • starch — the best choice of formulators
  • natural gums — due to its property to swell in water
  • cellulose derivatives (methocel, Avicel, alginates SCMC)
  • Starch — 5-20% of tablet weight.
  • Starch derivative — Primogel and Explotab (1-8%)
  • Clays- Veegum HV, bentonite 10% level in colored tablet only
  • Cellulose
  • Cellulose derivatives- Ac- Di-Sol (Na CMC)
  • Alginate
  • PVP (Polyvinylpyrrolidone), cross-linked

Super disintegrants: Swells up to ten fold within 30 seconds when contact water.

  • Example: Crosscarmellose- cross-linked cellulose, Crosspovidone- cross-linked povidone (polymer), Sodium starch glycolate- cross-linked starch.
  • A portion of disintegrant is added before granulation and a portion before compression, which serve as glidants or lubricant. Evaluation of carbon dioxide in effervescent tablets is also one way of disintegration

4. Lubricants

These are substances which:

  • improve the rate flow of tablet granulation
  • prevent adhesion of the tablet, material to the surface of the dies and punches
  • reduce particulate friction
  • facilitate the ejection of the tablets from the die cavities
  • The quantity of the lubricant, varies, being as low as 0.1% and in some cases, as high as 5%
  • Poor lubrication can be detected by the “scratch” marks on the edges of the tablets; another is the “screeching” sound of the machine.

Examples of raw materials employed as lubricants are:

  • stearates of magnesium and zinc
  • talcum powder (asbestos free)
  • sodium benzoate
  • mixture of sodium benzoate and sodium acetate
  • colloidal silicone dioxide
  • Leucine
  • carbowax 400
  • Glidants- Corn Starch — 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.

5. Coloring Agents

Coloring agents are added to tablet granulations for the following purposes:

  • for improvement of aesthetic appearance
  • to provide control of the product during its manufacturing

6. Flavoring Agents

These are substances added to tablet formulations mainly to “mask” the undesirable flavor of certain medicaments.

  • for improvement of aesthetic appearance
  • to provide control of the product during its manufacturing

Examples of raw materials employed as flavoring agents:

  • sugars (natural or artificial)
  • essential oils ( peppermint, lemon, orange, vanilla, strawberry, banana, and the likes)
  • fruit acids

Sweetening agents

  • For chewable tablets: Sugar, mannitol.
  • Saccharine (artificial): 500 time’s sweeter than sucrose
  • Aspartame (artificial): methylester dipeptide of phenylalanine and aspartic acid

7. Adsorbents

These are substances capable of holding quantities of fluids or moisture in an apparently dry state.

Examples of raw materials employed as adsorbents:

  • carbonates of magnesium and calcium
  • oxides of magnesium and aluminum
  • kaolin, bentonite
  • veegum
Sugar coating machine
 

Sugar coating machines are used for average coating and polishing of formed tablets and pills in pharmaceutical and food industry.



   
WORKING PRINCIPLE
  • ACTION: The sugar coating vessel or pot is elevated, allowing electric heater or gas to be placed directly under it.

Other Application:
  • These machines apply many layers of sugar on the surface of tablets/pills for better protection.
  • Can also be used for aqueous or film coating of products.

In film coating:
  • The process involves pre-heating the solution in the coating vessel and then introducing the product to be coated in it.
  • After layers of coat has been applied, the product is dried and cooled with uniform finishing.

Benefits of Sugar Coating Machine
  • Performs dual function of sugar and film coating
  • Uniform application of coats
  • Effective drying
  • Easy to clean and maintain
  • Higher productivity

STAGES INVOLVED IN THE PRODUCTION OF SUGAR COATED TABLETS
  1. Sealing of the tablet cores
  2. Subcoating
  3. Smoothing (or grossing)
  4. Colouring
  5. Polishing
  6. Printing
 
SEALING
  • An aqueous process during which the tablet cores are thoroughly wetted by syrup applications.
  • TABLET SEALANTS are generally water-insoluble polymers or film formers applied from organic solvent solution
Tablet Sealants
  1. Shellac — very commonly used and is best in combination w/ PVP (prevents hardening of polymer)
  2. Cellulose acetate phthalate
  3. Polyvinyl acetate phthalate
  4. Acrylate polymers

Subcoating
  • This is necessary for having a completely smooth profile with no visible edges remaining from the original tablet core
2 Methods of Subcoating
  1. Application of gum/sucrose solution followed by dusting with powder and then drying
  2. Application of suspension of dry powder in the gum/sucrose solution followed by drying
    Gum: acacia or starch derivative, gelatin, acacia — aid in the adhesion of powder fillers such as calcium carbonate or talc

Smoothing or Grossing
  • Subcoated tablets that were previously made were rough, and these tablets are made perfectly smooth by successive applications of dilute syrup.
  • The tablets are subjected to drying air after each application

Color-coating
  1. Water-soluble dyes

    — traditional method; process is prone to coating faults eg, poor and uneven coverage, and variation in color from batch to batch

  2. Water-Insoluble pigments (Aluminum lakes or Iron oxides)

    — Easier to use and permit comparatively fast color coating


Polishing
  • The tablets receive one or two applications of a wax dissolved in an organic solvent
  • Optimum temperature and humidity conditions are to consider

Printing
  • For identification since intended monogram is not feasible

Methods of Coating syrup application
  1. Manually using a ladle

    Traditional panning equipment, capable of achieving impressive results in skilled hands but this technique is not easy to control in terms of modern GMP requirements

  2. Automatic control

    These control devices allow programmed variation in dose volume, rolling time, and drying time


Other equipment having efficient drying ability
  1. Accela Cota — Manesty machines, Liverpool, England
  2. Hi-Coater — Freund Company, Japan
  3. Driacoater — Driam Metallprodukt GmbH, Germany
Accela-Cota
Driacoater
Hi-Coater
 

Ideal Characteristics of Sugar coated tablets

specifications and any appropriate compendial requirements

  1. Ideally be of perfectly smooth rounded contour with even color coverage
  2. Aesthetic appeal and should be polish to a high gloss
  3. Any printing should be distinct with no smudging or broken print
Film Coating
  • More modern
  • Made usually by a spray method
  • Usually specialized equipment is employed
Film Coating Machine
  • High Efficiency Film Coating Machine are widely used for coating various tablets, pills and sweets with organic film, water-soluble film, slow and controlled release film and sugar film etc in pharmaceutical, nutrition, foodstuff, and sweets industries.
Characteristics:
  • high efficiency
  • low energy consumption
  • easy to clean and operate
  • take small floor area

The machine adopt advanced design concept, has compact structure, meet cGMP standard completely.

Process Description
  • The coating liquid contains polymer in a suitable liquid medium together with other ingredients eg: pigments and plasticizers
  • This solution is sprayed on a rotated, mixed tablet bed
  • The drying conditions permit removal of the solvent leaving thin deposition of coating material
Coating Solution Formulation
  • Polymer
  • Solvent
  • Plasticizers
  • Colorants

POLYMER
  • Cellulose derivatives are most commonly used
  • The film forming materials used in film coatings are ethyl cellulose, polyvinylpyrolidone, hydroxymethylpropyl cellulose.
  • These are soluble in water as well as in nonaqeuous organic solvents.
Other Polymers
  • Methyl hydroxyethylcellulose, Povidone USP, Sodium CMC, PEG-4000
  • Acrylate-based: for plain film coatings
  • Other types are modified designed to give gastric-insoluble films or controlled release properties
  • Shellac or cellulose acetate phthalate in combination w/ PEG
Enteric coating polymers
  • Cellulose acetate phthalate, Acrylate polymers, Hydroxypropyl methyl cellulose phthalate, Polyvinyl acetate phthalate

SOLVENT

Modern techniques rely on water as a solvent because of the significant drawbacks that readily became apparent due to the use of organic solvents.

Solvents used for coating:
  • Ethanol, Methanol, Isopropanol, Chloroform, Acetone, Methylene chloride, Methylene ethyl ketone

PLASTICIZERS
  • PEG, propylene glycol, glycerol and its esters and phthalate esters
  • Only water-miscible plasticizers can be used for aqueous-based spray systems

COLORANTS
  • Choice is water-insoluble pigments
  • This overcomes color variation problems encountered with dye
  • Their opaque properties resulted in efficient coloring of thin coating used in film coating techniques

Supercell™ Tablet Coater
  • Revolutionary tablet coater that accurately deposits controlled amounts of coating materials on tablets, even if they are extremely hygroscopic or friable.
Advantages
  • Continuous coating (Short processing time)
  • Flexible modular design
    — R & D batch size (Minimum batch size of 30 grams)
    — Production capacity of 6 cells coats 200,000 tablets per hour of 120 mg tablets
  • Enhancing technology
    — Difficult-to-coat shapes, Friable tablets, Multi-layer coating
  • Enabling Technology
    — “Low humidity process” suitable for moisture sensitive materials
    — Accuracy of coating