Oral Drug

Delivery Systems
A formulation or device that safely brings the therapeutic agent to a specific body site
at a certain time rate to achieve an effective concentration at the site of drug
action.”

Conventional Dosage Form

Tablets
References
Aulton’s Pharmaceutics: The science of dosage form design.
3rd Edition
p 411 -513
Conventional oral dosage forms
• Tablets
• Capsules
• Solutions
• Suspensions
 Tablet types
Tablets are solid dosage forms usually prepared with the aid of suitable
pharmaceutical excipients primarily by compression
Some tablets are scored, or grooved, which allows them to be easily broken
into two or more parts.
•For immediate release
tablets, drug is intended to
be released rapidly after
Immediate Delayed
Cumulative amount of released drug

administration and achieve

steady - state plasma
concentrations quickly and Extended
maintained with appropriate
repetition of the dosage
forms.
•The most common type of
Modified release
tablet is immediate release.
Because they have different
release profiles, immediate
release and modified
release tablets contain
different excipients Time
• Based on drug release characteristics
 Tablet Additives
1. Diluents / fillers (necessary bulk).
lactose, cellulose, glucose, sucrose, starch, mannitol
2. Binding agents (maintain tablet integrity).
starch, gelatin, methyl cellulose, polyethylene glycol
3. Glidants
talc, silica, magnesium stearate
4. Lubricants
magnesium stearate, sodium lauryl sulphate, polyethylene glycol, liquid parafin
5. Disintegrating agents (promote tablet breakup).starch, cation exchange resins,
cross-linked polyvinyl pyrrolidone, cellulose
6. Miscellaneous additives such as colorants and flavorants.

• Therapeutically inactive
• They are there to help control the production process and make sure it runs
smoothly and to control the properties of the tablet. e.g dissolution
• Fillers are used when the dose of the active is small, and so need add fillers to
make up the mass to be about 50 mg, the minimum weight of a tablet.
• Many substances used as excipients can be described as multifunctional and do
more than one job (starch & cellulose)
 Disintegrating Tablets
• Conventional tablets

Tablet
• Chewable tablets disintegration
• Effervescent tablets faster than
conventional
• Lozenges compressed
• Sublingual / buccal tablets tablets

• Tablet is a compressed powder. Powders that are not compressed are sometimes used
for rapid, systemic effect.
• Conventional tablets are the most common type of tablet. They are meant to be
swallowed intact (coated or uncoated) and the drug release by disintegration and
dissolution in a relatively short amount of time.
• Goal is fast and complete drug release in vivo.
• The design of the tablet depends on the intended use. Ones that are swallowed
whole are meant for systemic treatment - when they disintegrate and are
absorbed in the GIT. Can also be used for local delivery - e.g. in mouth/throat or
in the stomach to lower pH

• Chewable tablets = mechanically disintegrated in the mouth and so don’t

usually contain a disintegrant excipient. But drug swallowed and dissolved in the
intestine. Used to get a quick and complete tablet disintegration and so a rapid drug
effect e.g. antacids and vitamins. Good for children and the elderly who have
trouble swallowing tablets. Can be used when no water available

• Effervescent = put into a glass of water before administration. Fizz = CO2 is

liberated from the reaction in water between carbonate (CO3) or bicarbonate and a
weak acid (e.g. citric or tartaric acid). Fizz facilitates tablet disintegration and rapid
drug dissolution (few mins).
• Get a rapid drug action. The water solution used to dissolve the effervescent tablet
then contains sodium bicarbonate. This increases the pH of the stomach and
stimulates gastric emptying. SO the drug rapidly leaves the stomach and can be
absorbed from the SI and so rapidly be bio-available. Good for when you don’t
want gastric irritation - as can be caused by aspirin

• Lozenges = retained in the mouth and dissolve slowly there in the saliva.

• Drug is dissolved in the saliva. Used for local medication of the mouth / throat e.g.
local anaesthesia, antiseptic. No disintegrants in these tablets. They do have
flavours and colours though. Choice of fillers and binders is important because they
have to have a good taste and also a good “Mouth feel”. (e.g. glucose)

• Buccal = drug release in the mouth and then systemic uptake.

Get a rapid systemic uptake and avoids first pass metabolism in the liver.

Often small tablets and porous to facilitate rapid disintegration.

 Tablet
Types

1. Multiply compressed Tablets are prepared by subjecting the fill material to more
than a single compression. 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.

2. Layered tablets are prepared by initial compaction of a portion of fill material in a

die followed by additional fill material and compression to form two-layered or
three-layered tablets, depending on the number of separate fills.
3. Sugar-Coated Tablets: Colored or an uncolored sugar layer. The coating is water
soluble and quickly dissolves after swallowing. The sugarcoat protects the enclosed
drug from the environment and provides a barrier to objectionable taste or odor. The
sugar-coat also enhances the appearance of the compressed tablet and permits
imprinting of identifying manufacturer's information. Among the disadvantages to
sugar-coating tablets are the time and expertise required in the coating process and
the increase in size, weight, and shipping costs. Sugarcoating may add 50% to the
weight and bulk of the uncoated tablet.

4. Film-Coated Tablets : Thin layer of a polymer capable of forming a skin like film.

Usually colored and has the advantage over sugar coatings in that it is more
durable, less bulky, and less time- consuming to apply.

5. Enteric-Coated Tablets: have delayed-release features.

6. Gelatin-Coated Tablets: A recent innovation (Gelcap). It is a capsule shaped
compressed tablet that allows the coated product to be about one-third smaller
than a capsule filled with an equivalent amount of powder. The gelatin coating
facilitates swallowing, and gelatin-coated tablets are more tamper evident than
unsealed capsules.

7. Buccal and Sublingual Tablets : They are flat, oval tablets intended to be
dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublingual
tablets) for absorption through the oral mucosa.

• Buccal tablets are designed to erode slowly, whereas those for sublingual use (such
as nitroglycerin) dissolve promptly and provide rapid drug effects. They enable oral
absorption of drugs that are destroyed by the gastric juice and/or are poorly
absorbed from the GIT.
8. Lozenges or Troches are disc-shaped solid dosage forms containing a medicinal
agent and generally a flavoring substance in a hard candy or sugar base
(Strepsils).

They are intended to be slowly dissolved in the oral cavity, usually for local
effects, although some are formulated for systemic absorption.

9. Chewable Tablets: Have a smooth, rapid disintegration when chewed or allowed to

dissolve in the mouth, have a creamy base, usually of specially flavored and colored
mannitol.

• Chewable tablets are especially useful for administration of large tablets to children
and adults who have difficulty swallowing solid dosage forms.
10. Effervescent tablets are prepared by compressing granular effervescent salts that
release gas when in contact with water. The “bubble action” can assist in
breaking up the tablets and enhancing the dissolution of the active drug.

11. Immediate-Release Tablets are designed to disintegrate and release their

medication with no special rate-controlling features, such as special coatings and
other techniques.
12. Instantly Disintegrating or Dissolving Tablets (rapidly dissolving tablets or RDTs)
are characterized by disintegrating or dissolving in the mouth within 1 minute, some
within 10 sec.

• Tablets of this type are designed for children and the elderly or for any patient who
has difficulty in swallowing tablets. The original fast-dissolving tablets were molded
tablets for sublingual use.

• Préparation Techniques:

• 1) Lyophilization or 2) soft direct compression where super disintegrants are

incorporated with a small quantity of effervescent material.

• Packaged in cards or bubble- type packaging with the backing peeled back to reveal
the tablet where it is then removed when required for administration. Problems:
drug loading, taste masking, friability, manufacturing costs, and stability of the
product. Taste by a flavoring technique or by microencapsulation or nano-
encapsulation.
13. Extended-release tablets (sometimes called controlled-release tablets) are
designed to release their medication in a predetermined manner over an
extended period.

14. Vaginal tablets, also called vaginal inserts, are uncoated, bullet-shaped or ovoid
tablets inserted into the vagina for local effects.

• They are prepared by compression and shaped to fit snugly on plastic inserter
devices that accompany the product.

• They contain antibacterials for the treatment of nonspecific vaginitis caused by

Haemophilus vaginalis or antifungals for the treatment of vulvovaginit /
candidiasis caused by Candida albicans and related species.
 1.Sugar coated

Why coating? ease swallowing,

pleasant taste
2. Enteric coated
1. Protect tablet ingredients - perhaps from hydrolysis
cellulose acetate phthalate
2. Mask taste of bitter drugs polyvinyl acetate phthalate
3. Identification of tablet - colours, printing etc acrylic derivatives
4.Easier handling during automated packaging - slide without friction through
machines
5. Functional coating to give enteric coating / controlled release properties
TYPES OF COATING
• Sugar coat is the traditional method for coating. Use sucrose-based solutions. It is a multi-
stage process that takes up to 8 h to produce (long time). Nice and shiny looking.
• They are also polished with beeswax. Use edible inks to write manufactures name on tablet.
• Enteric coating is a functional coat. Protects the tablet core from disintegration in the acid
environment of the stomach
Why?
1. Prevent acid attack on active ingredients in tablet.
2. Protect stomach from irritant effects of drugs.
3. Facilitate absorption of drugs distal to the stomach.
The polymers used to make the enteric coat are soluble at specific pHs higher than those in the
stomach.
 increasing surface area for dissolution

Disintegration Deaggregation

Intact tablet Granules Primary drug

particles

Low rate of Moderate rate of Relatively

dissolution dissolution rapid rate of
dissolution

•When a drug is formulated as

a compressed tablet, a huge
reduction in the surface area
occures.
•Many bioavailability problems
are associated with this
reduction in surface area and
the need to generate a fine
well dispersed suspension in
the GIT
Drug in solution in •Steps in the disintegration and
gastrointestinal fluids dissolution prior to absorption of a
poorly water soluble drug from a
Absorption tablet
•In order to enhance the
bioavailability, it should be possible
to increase the rate of
Drug in blood
disintegration and deaggregation
of water-soluble diluents
 Compressed Tablet Manufacture
• Compressed tablets may be made by 3 basic methods: wet granulation, dry granulation &
direct compression.

1) Wet Granulation
Widely employed method. The steps required are (a) weighing and blending the ingredients, (b)
preparing a dampened powder or a damp mass, (c) screening the dampened powder or
damp mass into pellets or granules, (d) drying the granulation, (e) sizing the granulation by
dry screening, (f) adding lubricant and blending, & (g) forming tablets by compression.

• a) Weighing and Blending

• Fillers include lactose, microcrystalline cellulose, starch, powdered sucrose, and
calcium phosphate (what are the factors affecting the choice of the filler).
• Disintegrating agents include croscarmellose, corn and potato starches, sodium starch
glycolate, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), crospovidone
and alginic acid. Often a portion (sometimes half) is reserved and added to the finished
granulation prior to tablet formation (double disintegration of tablets).

• b) Preparing the Damp Mass

• Among binding agents are solutions of povidone, an aqueous preparation of cornstarch
(10% to 20%), glucose solution (25% to 50%), methylcellulose (3%),
carboxymethylcellulose, and microcrystalline cellulose.
• Nonaqueous solution may be used.
• Overwetting and underwetting
c) Screening the Damp Mass into Pellets or Granules
• This may be done by hand or with special equipment that
prepares the granules by extrusion through perforations in the
apparatus.
• The resultant granules are spread evenly on large lined trays
d) Drying the Granulation
e) Sizing the Granulation by Dry Screening
• In general, the smaller the tablet to be produced, the smaller
the granules. Screens of 12- to 20-mesh size (0.85 – 2 mm) are
generally used for this purpose.
f) Adding Lubrication and Blending
• They improve the flow of the granulation in the hopper to the
die cavity. They prevent adhesion of the tablet formulation
to the punches and dies during compression.
• They reduce friction between the tablet and the die wall during
the ejection of the tablet from the machine.
• They give sheen to the finished tablet.
• Lubricant is dusted over the spread-out granulation through a
fine mesh screen.
• Among the more commonly used lubricants are magnesium
stearate (most common), calcium stearate, stearic acid,
talc, and sodium stearyl fumarate.
All-In-One Granulation Methods : Continuous fluid bed process, using a single piece of
equipment, the fluid bed granulator.
2) Dry Granulation
• The powder mixture is compacted in large pieces and subsequently broken down or sized into
granules. The active ingredient or the diluents must have cohesive properties.

a) Slugging : slugged, or compressed, into large flat tablets or pellets about 1 inch in diameter.
• The slugs are broken up by a mill and passed through a screen of desired mesh for sizing.
Lubricant is added in the usual manner, and tablets are prepared by compression.

b) Roller Compaction
• The compacted material is broken up, sized, and lubricated, and tablets are prepared by
compression in the usual manner.
• Binding agents (dry binders) used in roller compaction formulations include methylcellulose or
hydroxymethylcellulose.
3-Direct Compression Tableting
• Free flowing cohesive granular drugs (e.g. potassium chloride).
• Directly compressible vehicle excipients include fillers, such as spray-dried lactose,
microcrystals of alpha-monohydrate lactose, sucrose-invert sugar-corn starch mixtures,
microcrystalline cellulose, crystalline maltose, and dicalcium phosphate.
• Disintegrating agents, such as direct compression starch, sodium carboxymethyl starch,
cross-linked carboxymethylcellulose fibers, and cross-linked polyvinylpyrrolidone.
• Lubricants, such as magnesium stearate and talc.
• Glidants, such as fumed silicon dioxide.

Tableting (Compression Step)

• Compress a tablet formulation within a steel die cavity by the pressure exerted
by the movement of two steel punches, a lower punch and an upper punch.
• Rotary tablet machines (continuous rotating movement of the punches).
• Double rotary tablet presses- two tablets for each die (produce 10,000 or more per min).
• A consequence of high-speed production is the increased occurrence of lamination (horizontal
striations) and tablet capping (top part separation), in which the top of the tablet separates
from the whole because the fill material does not have enough time to bond after compression.
• Sometimes it is related to air entrapment during direct compression, caused by punches that
are not immaculately clean and perfectly smooth or by a granulation with too much fines.
• Tablets that have aged or been stored improperly also may exhibit splitting or other physical
deformations.
Punch & die set:
A.Upper punch.
B. Die cavity.
C. Die.
D. Lower punch.