Tablets

Chapter 8: TABLETS

Ø  Solid dosage forms containing medicinal  substances with or without suitable diluents

Ø  Most widely used dosage form

ADVANTAGES:

1. Precision of dosage form
2. Durability of physical characteristics for extended period of storage
3. Stability of chemical and physiological activity
4. Convenience of administration

DISADVANTAGES:

1. Irritant effects of the GI mucosa by some solids (aspirin)
2. Possibility of bioavailabilty problems resulting from slow disintegration and dissolution

CLASSIFIED ACCCORDING TO THE METHOD OF MANUFACTURE:

1. Compressed Tablets – usually prepared by large scale production methods
2. Molded tablets – small scale production

COMPRESSED TABLETS

-          Are formed in the process of pressing powdered crystalline or granular substances alone or in combination with excipients to form a compact adherent of pre-determined shape

3 Main methods of manufacture:

1.      WET granulation

a.     Weighing and blending

b.     Preparing dampened powder

c.     Screening of damp mass to form pellets and granules

d.     Drying of granules

e.     Sizing by dry screening

f.        Adding lubricant and blending

                                                               i.      Most used lubricant: Magnesium stearate

g.     Compressed to form tabs

2.      FLUID BED PROCESS

a.     Fluidized air

3.      DRY granulation

a.     For those that degradein moisture

                                                               i.      Slugging

                                                             ii.      Roller compaction

                                                            iii.      Tabletting

1.      LAMINATION- horizontal striation

2.      CAPPING- top of the tablet separates from whole, not enough bond

4.      Direct Compression

a.     Likes of Potassium chloride,possess free flowing properties that enable to compress directly

Types of compressed tablets

1.      SUGAR COATED TAB

a.       Contains sugar coating

b.      Such coating may be colored and are beneficial in covering up drug substances possessing objectionable tastes and odors and in protecting materials sensitive to oxidation

I.                     Waterproofing and Sealing

1.      Using shellac

II.                   Subcoating

III.                  Smoothing

IV.               Finishing and coloring

V.                 Polishing

2.      FILM COATED TABLETS

a.       Covered with an thin layer of water soluble material

b.      A number of polymeric substancs with film formingproperties may be used

c.       Film coating imparts the same  general characteristics as sugar coating with added advantage if a greatly reduced time period required for the coating operation

I.                     Film former: cellulose acetate phthalate

II.                   Alloying substance: water solubiliy/permeability :Polyethylene glycol

III.                  Plasticizer: Flexibility and elasticity- Castor oil

IV.               Surfactant

V.                 Opaquants colorants

VI.               Sweeteners

VII.              Glossant: luster: beeswax

VIII.            Volatile solvent: allow spread  over the tab; rapid evaporation: alcohol mixed with acetone

*due to environmental concerns:

Aquacoat is used. Water- based

30% ethyl cellulose pseudolatex

                                    PROBLEMS with FILM COATING

1.      Picking- appearance of small amounts of film fragments

2.      Peeling-  large amounts

3.      Orange Peel Effect- roughness of the tab, failure to coalesce

4.      Mottling- Uneven distribution of color

5.      Bridging- Filling in score line or intended logo

6.      Tablet erosion- Disfiguration of tablet due to over exposure to coating soln

3.      ENTERIC COATED TAB

a.       Coated with the substances that resist solution in gastric fluid but disintegrate in the intestines

b.      Enteric coating can be used for tablet containg during the substances which are inactive or destroyed in the stomach for which irritate the mucosa or as means of delayed release of the medication

I.                     USES PHTHALATES of sorts

II.                   To dissolve at pH 4.8 and greater

4.      MULTIPLE COMPRESSED TAB

a.       More than 1 compression cycles

b.      The tablets are prepared by 2 REASONS:

:To separate physically or chemically incompatible ingredients

:To produce repeat action /prolonged action tablet

c.       Can be used to separate incompatible drug to give an enteric coating to core tablets

5.      PROLOGED- ACTION TAB

a.       Formulated to release the drug substances in a manner to provide medication over the period of time

I.                     TYPES OF PROLONGED ACTION TAB

1.      DELAYED—ACTION- release of drug substances is prevented for an interval of time after administration or until the certain physiological conditions exist

2.      REPEAT-ACTION TAB- periodically release a complete dose of drug substances to the GI fluids

3.      EXTENDED- RELEASE TAB-continuously release increment of the contained drug substances in  GI fluid

6.      TABLETS FOR SOLUTION

a.       To be used for preparing solutions or imparting given characteristics to solutions must be labeled to indicate that they are not be swallowed

EXAMPLE: HALAZONE TABLET FOR SOLN

7.      EFFERVESCENT TAB

a.       In addition to the drug substance, these may contain sodium bicarbonate and an organic acid (tartaric acid and citric acid)

b.      In the presence of water, these additives reacts liberating CO2 which acts as DISINTEGRATOR and produces EFFERVESCENCE

8.      TABLETED SUPPOSITORIES OR INSERTS

a.       Occasionally vaginal suppositories such as METRONIDAZOLE tablets areprepared by compression

b.      In this case, as well as for any tablet intended for administration other than by swallowing, the label must indicate the manner which it is to be used.

9.      BUCCAL AND SUBLINGUAL TAB

a.       Small flat oval tab

b.      Tablets that are intended for buccal: by insertion into the buccal pouch dissolve and erode slowly

SUBLINGUAL

a.     NITROGLYCERIN AND ISOPROTERENOL HCL placed under tongue

b.     Dissolve rapidly and drug substances are readily absorbed by this term of administration

10.  CHEWABLE TABS

a.       Pleasant tastingtablets

b.      NO DISINTEGRANTS

c.       Wet granulation and compression

d.      MANNITOL- MOST used excipient for chewables 50% of the entire wt

e.      XYLITOL- mau be used, sweeter than mannitol; has desiabe negative heat of soln leaving COOL MOUTH FEEL upon dissolution

f.         

MOLDED TABLETS OR TABLET TRITURATES

-usually made from moist material using a triturate mold which gives them the shape of cut sections of a cylinder

- such tabletsmust be completely and rapidly soluble

- problems arising from compression of these tablets falure to find a lubricant that is completely water soluble

1. DISPENSING TAB

- provide a convenient quantity of poten drug that can be incorporated readily into powder and liquids thus circumventing the necessity to weigh small scale

- supplied primarily as a convenience for EXTEMPORANEOUS COMPOUNDING and should NEVER BE USED AS DOSAGE FORM

2. HYPODERMIC TAB

- soft readily solube tablets tht were originally used for preparation of solutions to be injected

- since stable parenteral solution are non available for most drug substances, there is no justification for the use of hypodermic tablets for injection

-their use is discouraged due to RESULTING SOLUTIONS NOT STERILE

COMPRESSED TAB

-  WELL-MADE COMPRESSED TAB POSSESSES THESE ATTRIBUTES:

1. ability to withstand the rigors of the mechanical fxn involved in the production packaging  shipment and dispensing

2. freedom from defects such as cracks chipped edges , discoloration , specking and contamination

3. Reasonable chemical and physical stability during average storage conditions

4. Ability to release the medicament in a reproducible and predictable manner

The components that must be added to the therapeutic ingredient are classified acoording to their function and grouped into

1. ESSENTIAL COMPONENTS impart satisfactory characteristics to the formulation

1.      BINDER-  glue powders together and cause to form granules ; mpart cohesive properties to powdered materials

2.      DILUENT- make up the major portion of tab

3.      DISINTEGRANTS -  help tablet break up and dissolves to release the medicament for rapid dissolution

      b.     COMPRESSION AIDS IMPART SATISFACTORY compression characteristics

1. GLIDANTS –enable flow from hopper on to the table press to the die for consistent tile

2. LUBRICANTS- aid in releasing the compresses tablet from the die

3. ANTI-ADHESIVES- to prevent the formation of residue films of tablet granulations in punches

      c. SUPPLEMENTARY COMPONENTS give additional desirable physical characteristics to finished tablet

1. COLOR- added for its aesthetic value to provide a control during manufacture and to distinguish one product from another

2. FLAVOR- same reason as color

3. SWEETENING AGENT- enhance taste of finished product especially when chewed

4. ADSORBENTS- capable of holding quantities of fluids in an apparently dry state

DILUENT

1. Lactose USP (Hydrous/Anhydrous)

            -  inexpensive

            - readily soluble

            - stable and generally inert

Net softened by frictional force of compression due to high MELTING POINT 202

DISADVANTAGE

1. BINDERS may have to be added when presence of drugs or some other substances interfere with cohesion

2. LUBRICANTS required

2. STARCHES

            - derived from the WHEAT CORN RICE and POTATO

            - ALSO UED AS BINDERS and DISINTEGRANTS

            - provide moisture balance even though the water content 12-14 %

            - they stabilize hygroscopic drugs and protect tablets of such material from deterioration before use

3. MANNITOL (powder, granules)

            - ADVANTAGES

            > highly desirable for WATER-SENSITIVE DRUGS
            >appropriate for chewable tab because its sweet taste and negative heat of soln

            -DISADVANTAGES

            >Expensive

4. SORBITOL

-ADVANTAGES

            > direct tableting

            -DISADVANTAGES

            >Very hygroscopic above 65% relative humidity

            >it may be blended with mannitol or other excipient to reduce moisture pick-up

5. SUCROSE

            ADVANTAGES

Ø  Provide additional sweetness

Ø  Serves as  BINDER since it has cohesive properties

Ø  Contributes to dissolution of the tablet since it is readily soluble       

DISADVANTAGES

Ø  Somewhat hygroscopic

Ø  Tends to form BROWN in contact with acidic and basic substances

6. MICROCRYSTALLINE CELLULOSE (Avicel)

            ADVANTAGES

Ø  Used for compression formulation

DIADVANTAGES

Ø  Presence of drug may necessitate addition of LUBRICANTS to formulation

BINDER

-          Efficiency of binders is dependent on the choice of the proper binding agent, quantity used and form of the binder when added

-          Choice of binder depends on the binding drug required to form granules and its compatibility with other ingredients as revealed by stability studies

-          Too much binder will result in hard tablets which will cause excessive wear if punches and dies because of heavy pressure required to compact the granules

-          Mottling of tab surface may also occur by these tablets are colored

-          Binders used as a solution is more effective the same amount of binder which is dispensed in dry form and moistened with the solvent

-          The binding soln can easily penetrate the film of adsorbed air coating each particle of a powerblend

RECOMMENDED BINDING SOLUTIONS ARE:

1. STARCH PASTE	10-20% W/W
2. AQUEOUS GELATIN SOLN	10-20% W/W
3. AQUEOUS GLUCOSE SOLN	25-50% W/W
ALCOHOLIC SOLUTION OF ETHYL CELLULOSE	5 % W/W

DISINTEGRANTS

-          The rate with which the active ingredient is released from the tablet mtrix is measures by disintegration time of the tablet

-          Major factor which affects disintegration  time is the disintegrants, its selection , quantity and mode of addition of the formulation

-          Other factor which can also affect disintegration time:

1. BINDERS

2. TABLET HARDNESS

3. LUBRICANT

           

-          Some material which functions as an disintegrants or chemically chemically classified as

1.  STARCH (CORN AND POTATO)

-          Most popular disintegrators

-          It has a great affinity for water and swell when moistened , thus facilitating the rupture of the tablet matrix. However, the starch does not swell at this temperature found in the gastric fluids

2. CLAYS (Bentonite and Veegum

3.  CELLULOSE

-  Methylcellulose

- sodium carboxymethylcellulose

                        - microcrystalline cellulose

                 4. ALGIN

                        - Alginic acid

                        - sodium alginate

               5.  gums

                        - Locust bean

                        - Karaya

                        - Guar

                        -tragacanth

            6. Effervescent mixture

                        - mixtures of the sodium bicarbonates and as acidulant such as tartaric acid or citric acid will effervesce when added to water

                        - gas pressure due to evolution of CO2 results in rapid disintegration of the tablet

Instantly Disintegrating or Dissolving Tablets

-          Dissolves approximately 15 to 30 seconds

-          Lyophilized foam- Zydis delivery system

-          Putting drug foam into a mold

USP Standards

1.      Weight variation: 10 tablets weighed. Average. Assayed

2.      Tablet thickness

3.      Hardness and Friability- minimum 4 kg force—SATISFACTORY TABLET

4.      Durability- FRIABILATOR- MAXIMUM WEIGHT LOSS OF less than 1% ACCEPTABLE

5.      Disintegration test; 3o minutes usually; nitroglycerin tab 2 min; buccal 4hrs

OTHER SOLID DOSAGE FORMS

1.      Lozenges- self care meds

2.      Lolliops- Fentanyl Actiq ( Cephalon) – Breakthrough pain for cancer

3.      Pills- small round