Ilovepdf Merged
Ilovepdf Merged
Tablets
Learning objectives:
May be intended for local effect in the GIT or for systemic effect
after absorption of active constituent
Disc shape
3. Effervescent Tablets
Compressed tablets disintegrate in water by liberation
of CO2 from acid-base reaction (disintegrants addition?).
Inexpensive
A Consideration of the Dose of Drug is the
Starting Point…
LOW DOSE (<25mg)
(Most of the tablet will be excipients)
Content Uniformity (mixing issues)
HIGH DOSE (>250mg)
(Most of the tablet will be drug)
Fluidity (flowability)
Compactibility
Tablet is a multi-component system:
• Drug
• Diluent
• Binder/Adhesive
• Glidant/lubricants/Antiadherents = (Lubricating agents)
• Disintegrants
• Coloring agents
• Flavoring agents
• Coating agent
Diluent (Filler)
• Bulking agent
• 10 – 50% Tablets weigh normally at least 50 mg.
• Must meet criteria Therefore, a low dose of drug per tablet
• Good compressibility requires the incorporation of a substance
• Must be stable into the formulation to increase the bulk
volume of the powder and hence the size of
• Physically
• Chemically the tablet.
• Must be biocompatible
Examples of Diluents (1)
Mainly CARBOHYDRATES but also some inorganic salts.
Lactose is the most common diluent in tablets.
• Properties:
• Good solubility in water
• Pleasant taste
• Non-hygroscopic (crystalline lactose)
• Non-reactive
• Good compactibility
• Available in different grades
• Very cheap
Examples of Diluents (2)
Spray processed lactose [Fast Flo lactose]
composed of lactose crystals and a small amount of amorphous
lactose
Amorphous dissolves more rapidly and has better compactibility
V. RAPID SOLUBILITY
Other sugars:
-glucose
-sucrose
-starch
Possible Incompatibilities
Classic example: Tetracycline formulated
with calcium phosphate.
DISINTEGRANTS
- Substances routinely included in tablet formulations
to promote water penetration and dispersion of the
matrix of the dosage form in dissolution fluids to
expose drug particles.
- Typically, disintegration of tablets should occur
within 15 minutes
Disintegration Process
DRUG IN SOLUTION
• There are two major mechanisms and factors affecting tablet
disintegration as follows:
A- Swelling
• Although not all effective disintegrants swell in contact
with water, swelling is believed to be a mechanism in
which certain disintegrating agents impart the
disintegrating effect, causing increase in internal
pressure of the tablet, and overcoming the
adhesiveness of other ingredients, causing the tablets
to fall apart
B: Porosity and Capillary Action (Wicking)
• Disintegrants that do not swell are believed to impart their
disintegrating action through porosity and capillary action.
• Tablet porosity provides pathways for the penetration of fluid
into tablets.
• The disintegrant particles themselves act to enhance porosity
and provide these pathways into the tablet.
• Liquid is drawn up or “wicked” into these pathways through
capillary action and rupture the interparticulate bonds
causing the tablet to break apart.
Types and Use Levels of Disintegrants
• Starch: 5-15%. (Swelling)
• Croscarmellose sodium: Modified Cellulose
(Sodium carboxymethyl cellulose which has been
crosslinked to render it insoluble). (Swelling & Wicking)
-AcDiSol®
Direct Compression: 1-3%
Wet Granulation: 2-4%
• Sodium Starch glycolate (Sodium carboxymethyl starch;
crosslinking reduces solubility) (Swelling)
SUPER DISINTEGRANTS
-Primojel®
-Explotab®
used at a concentration 4-6%
Sodium Starch Glycolate
Flavoring agents:
- Water-soluble flavours usually have poor stability. For this reason flavour oils or dry powders are
typically used.
- Oil flavors may be added to tablet granules just before compression
(WHY?) because they are sensitive to moisture and volatilization upon heating (during drying process).
- Since oils interfere with flowability and compressibility of the granules, minimum amount of the
flavouring agent (0.5% of the granulation) is used to avoid their negative effect on the tablet
characteristics.
Sweetening agents:
- Some sweeteners may come from the diluent (e.g. lactose and mannitol).
- Artificial sweeteners such as Saccharine and Aspartame may be also included.
- Saccharin is 400 times sweeter than sucrose but has an unpleasant after taste.
- Aspartame is 180 times sweeter than sucrose but is unstable in presence of moisture and
heat.
Colorants
• Used for Identification and to enhance patient compliance
• Coloring is often accomplished during coating, but a colorant can be included
in the formulation prior compaction (WG). The colorant can be added as a soluble
dye (wet granulation process) or insoluble powder (lakes) (direct compression).
• The coloring agent must be:
1- Safe (FDA approved)
2- It’s percentage must not exceed 0.05%
• FDA classifies the colorants into:
1- Food, drug and cosmetic type (FD&C Type)
2- Drug and Cosmetics type (D & C Type)
3- External Drug and cosmetic type (external D&C type)
These colors may be: Dyes, Natural Colors, Lakes, nondegradable, non-
absorbable polymers
Surface-active agents
• Surface active agents may be incorporated into tablets to
improve the wetting properties of hydrophobic tablets and
hence increase the rate of tablet disintegration.
• Besides that, surface active agents can lead to increase the
aqueous solubility of poorly water-soluble drugs in the GIT.
• Sodium lauryl sulfate is the classical example of surface
active agents.
INFLUENCE OF FORMULATION PARAMETERS ON TABLET
QUALITY ATTRIBUTES
•Or
1. Dry method (direct compression or dry granulation)
2. Wet method (wet granulation)
Granulation
Granulation is the process in which powder particles
are made to adhere to form larger particles called
granules. Pharmaceutical granules typically have a size
range between 0.2 and 4.0 mm
Reasons for granulations:
1. To prevent segregation of the constituents in the
powder mix
2. To improve the flow properties of the mix
3. To improve the compression characteristics of the
mix (charge vs size reduction)
Granulations
4. The granulation of toxic materials will reduce the
hazard of the generation of toxic dust which may
arise when handling powders
Wet
granulation
Dry
granulation
Granulation
Dry granulation
• The primary powder particles are aggregated under high
pressure. There are two main processes.
Either a large flat tablet (1 inch = 2.5 cm) (known as a 'slug')
is produced in a heavy-duty tableting press (a process known
as 'slugging') or
the powder is squeezed between two rollers to produce a
sheet of material ('roller compaction').
• In both cases these intermediate products are broken using a
suitable milling technique to produce granular material,
which is usually sieved to separate the desired size fraction.
The unused fine material may be reworked to avoid waste.
This dry method may be used for drugs that do not compress
well after wet granulation, or those which are sensitive to
moisture and heat.
Dry Granulators
• Dry granulation converts primary powder particles
into granules using the application of pressure
without the intermediate use of a liquid.
• It therefore avoids heat-temperature combinations
that might cause degradation of the product. What
about disintegration ability of the produced tablets
compared to those prepared with wet granulation?
• Two pieces of equipment are necessary for dry
granulation:
1. a machine for compressing the dry powders into
compacts or flakes, and
2. a mill for breaking up these intermediate products
into granules (hammer mill)
Dry Granulators
• Equipment:
A. Slugger (or heavy duty rotary press)
B. Roller compaction
Wet granulation
• It involves the massing of a mix of dry primary powder
particles using a granulating fluid followed by drying
• The fluid contains a solvent which must be volatile so
that it can be removed by drying, and be non-toxic.
• Typical liquids include water, ethanol either alone or in
combination. Therefore, wet granulation method is not
suitable for drugs which are unstable with heat or
moisture
• The granulation liquid may be used alone or, more
usually, as a solvent containing a dissolved adhesive
(also referred to as a binder or binding agent} which is
used to ensure particle adhesion once the granule is
dry.
Wet granulation
• Water:
Adv:
1. Commonly used for economical end ecological
reasons.
2. Inflammable
Disadv:
1. adversely affect drug stability, causing hydrolysis of
susceptible products, and
2. it needs a longer drying time than do organic
solvents.
Organic Solvent:
water-sensitive drugs are processed, or when a
rapid drying time is required.
Initial mixing
Screening of wet
mass
Dry screening
Primary particles
Direct Compression
Disadvantages
• due to difference in particle size and bulk density
between the drug and diluent may lead to stratification
within the powder which may then result in poor
content uniformity of the drug in the compressed
tablets (granulation?).
• Most materials cause relatively weak intermolecular
action that tend to hinder compaction (powder
relaxation).
• Because of the dry nature of direct compression, static
charge build up during mixing may prevent good
compaction (granulation?)
Steps in the different methods of Tablet Manufacture
1. Milling of drugs and excipients 1. Milling of drugs and 1. Milling of drugs and
2. Mixing of milled powders excipients excipients
3. Preparation of binder solution 2. Mixing of milled 2. Mixing of
powders ingredients
4. Mixing of binder solution with 3. Compression into 3. Tablet compression
powder mixture to form wet mass slugs
5. Coarse screening of wet mass 4. Screening of slugs,
using mesh screen then milling to get
6. drying of moist granules granules
7. Screening of dry granules 5. Mixing with half
through mesh screen disintegrant
8. Mixing of screened granules Mixing with lubricant
with half disintegrant then
Mixing with lubricant 6. Tablet compression
9. Tablet compression
Single punch tablet press
1. Die Filling
• This is normally accomplished by gravitational flow of the powder
from a hopper into the die
• After maximum applied force is reached, the upper punch leaves the
powder, i.e. the decompression phase.
3. Tablet Ejection
• During this phase the lower punch rises and the tablet is
subsequently removed from the die and die table by a punching
device.
Single-Station Press
Can produce up to 200 tablets per minute
Small scale production/formulation development
The powder is fed by gravity from the hopper shoe.
https://www.youtube.com/watch?v=owN3kEhw-nk
Upper punch
Hopper shoe
Die
Lower punch
Why coating?
Therapeutic
Technology Marketing
Aspects of tablet coating????
I- Therapy
1- Avoid irritation of esophagus and stomach
2- Avoid inactivation of drug in GIT
3- Improve drug effectiveness
4- Prolong dosing interval e.g., SR preparations
5- Improve patient compliance with easy of swallowing due to the
lubricant action
II- Technology
1- Reduce influence of moisture
2- Avoid dust formation from tablet core
3- Improve drug stability and separate incompatible materials
III- Marketing
1- Avoid bad taste
2- Distinguished product identity
3- Improve product appearance and acceptability
Types of tablet coating:-
1- Sugar coating
2- Film coating
3- Functionalized coating
3.1- Enteric coating
3.2- Controlled release coating
3.3- Specialized coating e.g., press
coating (time programmed release)
Sugar Coating
• Traditionally the sugar coating form the bulk of tablet
coating therefore, the film coating are the most modern
technology in tablet coating
• Description of tablets:
• Smooth, rounded and polished to a high gloss
• Process: Multistage process involving 6 separate operations:
• First of all we have to do de-dusting to avoid rough tablets
• 1- waterproofing or Seal tablet core
• 2- Sub-coating (largest layer)
• 3- Smoothing
• 4- Coloring
• 5- Polishing
• 6- Printing
https://www.youtube.com/watch?v=PVg8z4TnwxU
1- Sealing tablet core:
Application of a water impermeable polymer such as shellac, cellulose
acetate phthalate and polyvinyl acetate phthalate <Dissolved in
waterproofing solvent (alcohol)> which protect the core from
moisture and increase the shelf life.
2- Sub-coating: Main step
3-5 sub-coats of a sugar based syrup are applied. (rounding the tablet
and provide bonding between sugar coating)
The sugar and water syrup also contain agents such as acacia, PVP or
gelatin to enhance coating.
When the tablets are partially dried, they are sprinkled with a
dusting powder, usually a mixture of powdered sugar and starch,
but some times talc, acacia or chalk (Ca-carbonate).
3- Smoothing process: (Inside a clean pan)
Remove rough layers formed in step 2 with the application of thick sucrose
syrup (5-10 additional coatings) to get a smooth and rounded surfaces.
Between each addition we may prevent the sticking by adding dusting
powder
4- Finishing and <Coloring (optional)>: (Inside a clean pan)
Titanium based pigments are included in thin (low viscosity syrup) syrup
Between each addition we may prevent the sticking by complete drying
5- Polishing: to give a characteristic shine commonly using bees wax,
carnauba wax.
6- Printing: edible ink for characterization
Disadvantage of Sugar Coating?
• Tedious, time consuming (1 to3 days)
• Mottling and spotting of finished tablets
• Increase in tablet weight by 30 to 50%
• Batch to batch variation
• May affect tablet disintegration time
• Scored or grooved tablet
Film Coating??
• Modern approach to coating tablets, capsules or pellets by surrounding them with
a thin skin tight coating of polymeric material (increase the wt by only 3%). Good
for grooved tablets
(enteric coating is part of this type)
• Process:
• Single step process, which involving spraying a coating solution containing the
following;
- Polymer: 7-18%
- Solvent (aq. Or non aq)
- Plasticizer: dense, impermeable film, high gloss and mechanical strength
- Colorant
The solution is sprayed onto tablets followed by drying which facilitate the removal of
the solvent leaving behind the deposition of thin film of coating material around
each tablet.
Advantage of Film Coating?
1- One stage procedure, less time consuming (1-
3 hours)
2- Tablet weight increased by only 2 – 4%
3-More economic
4- It does not affect disintegration time of
tablets
5- Can be adapted for CR, SR or enteric coat.
Disadvantage:-
• There are environmental and safety implications of
using organic solvent
• financial expenses
1- Polymer
Film coating
Immediate Release Modified Release
2
UNOFFICIAL TESTS :
Appearance
Size and shape
Hardness (resistance to fracture)
OFFICIAL TESTS
Friability (resistance to attrition)
Dissolution test
Disintegration test
3
These factors must be
controlled during production
(in-process controls) and
verified after the production
of each batch to ensure that
established product quality
standards are met.
6
Dimensions :
The thickness or diameter of a tablet is determined by the diameter of the die, the amount
of fill permitted to enter the die, the compaction characteristics of the fill material, and
the force or pressure applied during compression.
The dimensions of the tablets, thickness & diameter are measured by using digital vernier
calipers, screw guage or automated equipment (resistance to crushing machine)
7
HARDNESS : (mechanical strength test= resistance to fracture)
8
It is a valuable test ,which influence the tablet dissolution & disintegration
Depending upon the type & concentration of the binding agent the hardness varies
Binding agents (eg) ; acacia mucilage ,starch paste , sugar syrup , methyl cellulose
dispersion etc.
9
• The greater the pressure applied during compression, the harder the
tablets.
• Certain tablets, such as lozenges and buccal tablets, that are intended
to dissolve slowly are intentionally made hard; other tablets, such as
those for immediate drug release, are made soft.
> 324 mg ±5 %
BP - OFFICIAL LIMITS
Tablet weight limit
80mg or less ±10 %
80mg – 250 mg ±7.5 %
> 250mg ±5%
13
Test procedure :
20 tablets were randomly selected for the test, every tablet in each batch should have uniform weight .
20 tablets are weighed individually. Average weight is calculated from individual weight of all tablets
The percentage difference in the weight variation should be with in the permissible limits.
14
Result :
Not more than two of the individual weights deviates from the average
weight by more than the percentage given in the pharmacopea and none
deviates by more than twice that percentage
15
FIGURE: Automatic weight, hardness,
thickness, and tablet diameter test
instrument for quality control. Using a
microprocessor and monitor for
visualization, the instrument
can test up to 20 samples at a time.
https://www.youtube.com/watch?time_continue=267&v=aGw4SMK9wO4
Content uniformity test :
This test is applied to assure uniform potency for tablets of low dose drugs
The test is applicable to tablets that contain 10mg / < 10mg (or) < 10%w/w of active
ingredients
procedure :
Select 30 tablets randomly from the batch
Out of 10 tablets 9 tablets must contain not less than 85% not more than 115% of
labelled drug content
10 th tablet may not contain < 75% or > 125 % of labelled drug content.
17
Result :
If there is any deviation then perform the assays individually for 20 tablets
Out of 30 tablets none may fall outside of the 85% to 115% range for the batch
to be accepted.
Various factors are responsible for the variable content uniformity in tablets.
This may include: Tablet weight variation, Uneven distribution of the drug in
the powder or granules, Segregation of the powder mixture during formulation
processes and poor flow, improper analysis.
18
Friability test: (mechanical strength test = resistance to attrition)
Friability problem is encountered with thin tablets ,large diameter tablets ,granules
(excessively dried or excessive fine granules )
19
The extent of friability is measured by using Roche Friabilator
It rotates at a rate of 25 rpm .10 tablets are weighed collectively & placed in
the chamber of friabilator.in the friabilator the tablets are exposed to rolling
resulting from free fall of the tablets within the chamber of friabilator
20
After 100 revolutions (4 min ) the tablets were taken out from the friabilator and intake
tablets were again weighed collectively.
W1 – W2
friability = --------------- × 100
W1
For the medicinal agent in a tablet to become fully available for absorption, the tablet
must first disintegrate and discharge the drug to the body fluids for dissolution.
Tablet disintegration also is important for tablets containing medicinal agents (such as
antacids and anti-diarrheals) that are not intended to be absorbed but rather to act
locally within the gastrointestinal tract. In these instances, tablet disintegration
provides drug particles with an increased surface area for activity within the
gastrointestinal tract.
22
• 6 tablets are taken, If 1 or 2 tablets fail to disintegrate completely,
repeat the test on 12 additional tablets.
• The requirement is met if not less than 16 of the total 18 units are
disintegrated.
• The apparatus consists of a basket and rack assembly containing six open-
ended transparent tubes of USP-specified dimensions, held vertically
upon a 10-mesh stainless steel wire screen.
• During testing, a tablet is placed in each of the six tubes of the basket, and
through the use of a mechanical device, the basket is raised and lowered
in the immersion fluid at 29 to 32 cycles per minute, the wire screen
always below the level of the fluid.
• For uncoated tablets, buccal tablets, and sublingual tablets, water at
about 37°C ± 2 serves as the immersion fluid unless another fluid is
specified in the individual monograph (such as simulated gastric or
intestinal fluid).
• For most normal release tablets, the max time permitted is 15 minutes.
(different limits exist for different types of tablets ex: fast disintegrating
tablets)
• Tablets are said to have disintegrated if no fragments (other than
fragments of coating) remains on the screen. Chewable tablets are not
required to comply with the test.
TABLET TYPE DISINTEGRATION TIME
Uncoated 15 minutes
Plain coated tablet 60 minutes
Enteric coated tablet 3 hours
Dispersible tablet 3minutes
Effervescent tablet ˂ 3 minutes
Sublingual tablet 4 hours
Buccal tablet 4 hours
Vaginal tablet 60minutes
chewable tablet not required
26
DISSOLUTION TEST :
This test measures the amount of time required for a given percentage of the drug
substance in a tablet to go into solution under a specified set of conditions.
Rate of drug absorption for drugs is often determined by rate of drug dissolution from
the tablet. It is intended to evaluate the physiological availability of the drug substances,
and ensures bioequivalence from batch to batch. (ININC)
27
• The dissolution medium for each drug is different, could be water or acidic medium
(0.1 M hydrochloric acid) or alkaline medium (alkaline buffers 6.8 ±0.05).
• Dissolution rate test is performed at 37 oC ± 0.5. Samples are removed from the
dissolution chamber at periodic intervals and analyzed for drug content using a UV
spectrophotometer or HPLC. Dissolution samples removed for assay should be
filtered.
• Most commonly, the results of dissolution tests are expressed in terms of the time
versus percent released of drug
• For tablet dosage form design purposes, and for critical product comparison,
however, the time required for substantially complete 80 to 90% release or amount
released versus time profiles are the most desired approach.
• 6 vessels are used according to the USP while 3 vessels are used according to the BP
• https://www.youtube.com/watch?v=FpkU123LVTc
Basket method Paddle method
Limits :
In stage 1 : 6 tablets were tested & are acceptable if all of the tablets are not less than
Q + 5%
In stage 2 : additional 6 tablets were tested .if all average of 12 tablets is greater than
or equal to Q & no unit is less than Q – 15%
In stage 3 : all the average of 24 tablets is greater than or equal to Q & if not more
than 2 tablets are less than Q - 15 % and no tablet is less than Q - 25 %
31
Factors affecting dissolution of drug
1. Physiochemical properties of the drug
• Polymorphic form: A metastable form of a solid has higher solubility
and dissolution compared to its stable counterpart.
• Particle size: The smaller the particle size of a solid, the larger the
particle surface area and the higher the dissolution.
• Salt form: A salt form of a drug has a higher aqueous solubility
compared to its conjugate acid or base, as well as higher dissolution.
• Hydrates versus anhydrates: The anhydrous form shows higher
dissolution than hydrates due to their solubility differences.
2. Factors related to tablet manufacturing
• The amount and type of binder can affect the hardness, disintegration, and dissolution of
tablets.
• The method of granulation, granule size, and size distribution can affect tablet dissolution.
• The concentration and type of disintegrants used, as well as the method of their addition, can
affect disintegration and dissolution.
• Compression force applied to tablet
3. Factors related to method of dissolution study
• Composition of the dissolution medium, pH, ionic strength, viscosity.
• Type of dissolution equipment.
• Temperature of the medium
• Volume of dissolution medium
• Intensity of agitation
• Sink or non-sink conditions (under a sink condition, the concentration of the drug should not
exceed 10 % of its maximum solubility in the dissolution medium in use)
Conclusion :
quality control tests are used for evaluating the quality of tablets
35
Capsules
19:11 1
What are capsules?
• Capsules are solid dosage forms in which drugs & inert
substances are enclosed in a soft or hard shell of
gelatin
3
Why use capsules?
• Capsules are conveniently carried
• Easily identified (Shape, colour, and manufacturer’s name)
• Easily taken
• There is no need for spoons or other measuring devices
• Are tasteless when swallowed
• Are more stable and have a longer shelf-life than their liquid
counterparts
• Pharmacists can use empty hard gelatin capsules for extemporaneous
compounding
4
Hard gelatin capsules
• Empty capsule shells are made of gelatin, sugar, and water
(for flexibility)
• They are clear, colourless, and essentially tasteless
• They may be coloured with various FD&C and D&C dyes
• Made opaque by adding agents such as titanium dioxide
• Many with caps and bodies of different colours
• Hard gelatin capsule shells are used in most commercial
medicated capsules
5
Hard gelatin capsules
Why was gelatin chosen to prepare capsules?
• Gelatin is non-toxic
• Soluble in biological fluids
• Excellent mechanical properties
6
The gelatin
8
The gelatin
• Hard gelatin capsules contain 13% to 16% of moisture
(low level which doesn’t support bacterial growth)
• If stored in high humidity moisture is absorbed
distorted and lose their rigid shape
• If stored in extreme dryness moisture is lost
brittle and crumble when handled
• Thus: maintain hard gelatin capsules in an
environment free from excessive humidity or dryness
9
The gelatin
Thus: maintain hard gelatin capsules in an
environment free from excessive humidity or dryness
HOW?
10
The gelatin
• Gelatin is insoluble but softens in cold water
• Gelatin can absorb water up to 10 times its weight
• Gelatin is soluble in hot water and in warm gastric
fluid (where gelatin capsules rapidly dissolve and
release its contents)
• Gelatin (being a protein) is digested by proteolytic
enzymes and absorbed in the GIT
11
Manufacturing hard gelatin
capsules
• Hard gelatin capsule shells = the capsule body + a
shorter cap
• The two parts overlap when joined
19:11 12
What Shape?
19:11 13
Sealing and self-locking
closures:
Hard gelatin capsules are made self-locking by
forming indentations or grooves on the inside of the
cap and body portions. When fully engaged, a positive
interlock is created between the cap and body
portions. This keeps the empty capsules joined during
shipping and handling.
000 00 0 1 2 3 4 5
19:11 15
Filling hard gelatin capsules
General steps for large-scale or small-scale preparation:
19:11 17
The powder mix
• Lubricants or glidants enhances flow properties
(important for high-speed automated filling)
• Lubricants/glidants: SiO2, Mg stearate, stearic acid, or
talc (0.25% - 1%)
• Mg stearate ↑ waterproofing → retard penetration by
GIT fluids → delay drug dissolution and absorption
• Surface-active agents (e.g. sodium lauryl sulfate)
facilitate wetting by the gastrointestinal fluids
19:11 18
e.g. Tetracycline capsules
19:11 19
The fill material
19:11 20
Other capsule fillings
• Tablets, small capsules, coated pellets, granules →
separate chemically incompatible agents/premeasured
amounts of potent drugs /modified release
• No aqueous liquids → water softens gelatin → leakage
• Fixed or volatile oils (which do not affect the stability
of the gelatin shells) can be placed in hard gelatin
capsules
• The liquid may be mixed with an inert powder to make
a wet mass or paste which may then be placed in
capsules . Alternatively, put liquids in soft gelatin
19:11 21
Filling the capsules (manual)
Sealed capsules
19:11 23
Capsule sealing
Sealing can be achieved by:
• Kapseals (Parke-Davis): using a colored gelatin band
• Sealing through heat-welding of cap & body at the
double wall at their juncture
• Sealing by a liquid wetting agent (water/ethanol)
• Extemporaneously: sealing by lightly coating the cap
inner surface with a warm gelatin solution
immediately prior to placement of the capsule body
19:11 24
Cleaning and polishing capsules
• The powder mix may be bitter or unpalatable → remove
powder before packaging or dispensing
• On a small scale: capsules are cleaned individually or in
small numbers with clean gauze
• On a large scale: capsule-filling machines have a
cleaning vacuum that removes any excess material from
the capsules surface
• 19:11 25
Soft gelatine capsules
26
Soft gelatin capsules
• Capsules consist of one piece hermetically-
sealed soft shells
•Made of gelatin to which glycerin or sorbitol
(polyhydric alcohol) is added as a plasticizer
• Need a preservative to retard microbial growth
• Preservatives → methylparaben and/or
propylparaben
27
Soft gelatin capsules
•Are mostly used to encapsulate and
hermetically seal: liquids, suspensions, and pasty
materials
•Are pharmaceutically elegant and are easily
swallowed
•Are able to hold a larger amount of liquid-based
formulations compared to tablets and hard
gelatin capsules
28
Soft gelatin capsules -
components
• Gelatin
•Plasticizing agents
•Water
•Miscellaneous excipients
29
Plasticizers
• Plasticizers are additives that increase the
plasticity of a material
• The mechanical properties of soft gelatin
capsules are controlled by the inclusion and
concentration of plasticizers
• Plasticizers: polyhydric alcohols (glycerol or
sorbitol) or their mixtures
• Plasticizer concentration is generally 20–30%
w/w 30
Plasticizers
• This concentration range determines the
mechanical properties of the soft gelatin
capsule
• Plasticizer concentrations > 30% w/w →
capsule is too flexible and tacky (sticky)
• Plasticizer concentrations < 20% w/w →
capsule is too brittle
31
Water
• Water is required during the manufacturing
process and in the finished product
• During manufacture of the soft gelatin
capsules: water concentration is 30 - 40% w/w
• In the finished/dried capsule: the water
concentration is 5–8% w/w
• Water ensures capsule flexibility
• Over-drying of capsules result a brittle product32
Miscellaneous excipients
• Colorants
• Opacifiers (TiO2): protect light-sensitive API’s
• Preservatives (methylparaben and/or
propylparaben)
33
Formulation of the fill
• The fill material is primarily liquid-based
• The therapeutic agent may be dissolved or
dispersed within the fill material
• There are several categories of fill material:
(1) lipophilic liquids
(2) self-emulsifying systems
(3) water-miscible liquids
34
Lipophilic liquids
• Include vegetable oils (volatile and non-
volatile) (e.g. soyabean oil), and fatty acid esters
• A limited number of drugs are soluble in these
materials → inclusion of co-solvents in
formulation . Alternatively, the drug fill may be
formulated as a suspension (requiring the
inclusion of viscosity-modifying agents)
35
Self-emulsifying systems
• Self-emulsifying systems are lipophilic liquids
that contain a non-ionic emulsifying agent (e.g.
Tween)
• Following release into the gastrointestinal tract,
the fill material rapidly emulsifies into small
droplets (with high surface area) → enhances
drug dissolution and absorption
36
Water or water-miscible
liquids
• High-molecular-weight alcohols, e.g. PEG 400, PEG
600
• Small concentrations of ethanol and water (< 5%) can
be used
• The drug can be dissolved or dispersed within the
solvent
• Liquids that can easily migrate through the capsule
shell are not suitable for soft gelatin capsules e.g.
Water or alcohols > 5%
37
Soft gelatin Capsule filling
https://www.youtube.com/watch?v=vkwoqyh5fL8
19:11 38
I. Kapseals (Parke-Davis) is:
19:11 39
Pulmonary drug delivery
Introduction
• Inhaled drug delivery is used for the treatment or prophylaxis of
airways diseases, such as bronchial asthma, chronic obstructive
pulmonary disease (COPD) and cystic fibrosis in order to deliver the
drug directly.
• The administration of a drug at its site of action can result in a rapid
onset of activity.
• Smaller doses can be administered locally and reducing the potential
incidence of adverse systemic effects and reducing drug costs.
Introduction
• The pulmonary route is also useful where
a drug is poorly absorbed orally, e.g.
sodium cromoglicate (anti-inflammatory
used for asthma treatment), or where it is
rapidly metabolized orally, e.g.
isoprenaline (Adrenaline agonist).
• The avoidance of first-pass metabolism.
• The lungs also used as a route for
delivering drugs having systemic activity,
because of its large surface area, the
abundance of capillaries and the thinness
of the air–blood barrier
Inhalation aerosols
• An aerosol (by atomization) is defined as a two phase system of solid
particles or liquid droplets dispersed in air or other gaseous phase,
having sufficiently small size to display considerable stability as a
suspension.
• The deposition of a drug/ aerosol in the airways is dependent on four
factors:
1. The physicochemical properties of the drug
2. The formulation
3. The delivery/ liberating device.
4. The patient (breathing patterns and clinical status).
Inhalation aerosols
• The most important physical property of an aerosol for inhalation is
its size.
Formulating and delivering therapeutic
inhalation aerosols
54 22-Apr-
12
1. Pressurized metered-dose inhalers (metered-dose inhalers (MDIs)
• In pMDIs, drug is either dissolved or suspended in liquid propellant(s)
together with other excipients, including surfactants, and presented
in a pressurized canister fitted with a metering valve.
• A predetermined dose is released as a spray on actuation of the
metering valve.
• The high-speed gas flow helps to break up the liquid into a fine spray
of droplets.
Containers
• Pharmaceutical aerosols may be packaged in tinplated steel, plastic-
coated glass or aluminium containers.
Propellants
• The propellants used in pMDI formulations are liquefied gases,
traditionally chlorofluorocarbons (CFCs) which are now largely
replaced by hydrofluoroalkanes (HFAs).
• At room temperature and pressure, these are gases but they are
liquefied by decreasing temperature or increasing pressure.
• The head space of the aerosol canister is filled with propellant vapour,
producing the saturation vapour pressure at that temperature.
• On spraying, drug and propellant are expelled and the head volume
increases.
• To re-establish the equilibrium, more propellant evaporates and so a
constant pressure system with consistent spray characteristics is
Advantages of pressurized metered-dose
inhalers
• Portability
• Low cost and disposability.
• Many doses (up to 200) are stored in the small canister and dose
delivery is reproducible.
• The inert conditions created by the propellant vapour, together with
the sealed container, protect drugs from oxidative degradation and
microbiological contamination.
Disadvantages of pressurized metered-dose
inhalers
• Difficult to deliver high doses.
• There is no information about the number of doses left in the MDI.
• Accurate co-ordination between actuation of a dose and inhalation
is essential.
Spacers -actuated metered-dose inhalers
• Some of the disadvantages of pMDIs (inhalation/ actuation
coordination and the premature deposition of large droplets high in
the airways) can be overcome by using extension devices or ‘spacers’
positioned between the pMDI and the patient
• Frequently employed with a pMDI, for administering aerosol
medications to young children.
Dry powder inhalers
• In dry powder inhaler (DPI) systems, drug is inhaled as
a cloud of fine particles.