Pharmaceutical Lesson 3.

2: Solid Dosage Form

Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester

o Deliquescent powders will absorb moisture from the

OUTLINE
1. Powders
2. Tablets
3. Capsules
4. Emulsions
Powders
Powders
 Most active and inactive pharmaceutical ingredients occur in
the solid state as amorphous powders or as crystals of
various morphologic structures.
 A dry substance composed of finely divided particles
 A type of pharmaceutical preparation, that is, a medicated
powder intended for internal (i.e., oral powder) or external
(i.e., topical powder) use
 Powders represent one of the oldest dosage forms
Advantages and Disadvantages
 Advantages:
o Powders being the solid preparation are more stable
than liquid and semi-solid preparations.
o Convenient forms, to dispense large doses of drugs.
o They can be best administered in powder form by
mixing them with food or drinks.
o Since powders are in the form of small particles they
offer a large surface area and are rapidly dissolved in
the gastrointestinal tract minimizing the problems of
local irritation.
o More convenient to swallow, faster dissolution and
absorption than tablets or capsules.
o Powders offer a lot of flexibility in compounding or
incompatible solids and possess good chemical stability
o They are easy to apply.
 Disadvantages:
o Time-consuming to prepare
o Less convenient to carry especially for bulk powders are
not suitable for administering potent drugs with a low
dose.
o Difficult to mask the unpleasant taste of the drugs.
o Light fluffy powders may be inhaled by infants leading to
breathing difficulties.
o Variable dose accuracy
o They can cause damage to the stomach, these should
be presented as enteric-coated tablets.
o Can be bitter, nauseating and corrosive drugs, if they
are meant for oral administration.
o Difficulty of protecting hygroscopic , deliquescent or
aromatic materials and not suitable for drugs which are
unstable in normal atmospheric conditions
Special Considerations
 Eutectics
o Powders may become sticky or pasty, or they may
liquefy when mixed together
o One can mix them with a bulky powder adsorbent
such as light magnesium oxide or magnesium
carbonate.
o Ex: Aspirin, Salicylic acid and Lidocaine
 Hygroscopic Or Deliquescent
o Hygroscopic powders will absorb moisture from the
air.
air to the extent that they will partially or wholly liquefy
o Ex: Sodium nitrate, Zinc chloride and Pepsin
 Efflorescent
o a crystalline powder that contains water of hydration
or crystallization
o powder will become sticky and pasty, or it may even
liquefy
o Caffeine, Cocaine and Codeine
Classification of Powders
BULK POWDERS
o Bulk powders may be classified as oral powders,
dentifrices, douche powders, dusting powders,
insufflations, and trituration.
 Bulk powders available in prepackaged amounts are:
o (a) antacids (e.g., sodium bicarbonate)
o (b)douche powders (e.g., Massengill powder)
o (c) topical anti-infectives (e.g., bacitracin zinc
o (d) brewer's yeast powder containing B-complex
vitamins and other nutritional supplements.
 ORAL POWDERS
o are supplied as finely divided powders or effervescent
granules. The finely divided powders are intended to be
suspended or dissolved in water or mixed with soft foods
such as applesauce prior to administration.
o Ex: Antacids & Laxatives
 EFFERVESCENT
o Effervescent granules contain sodium bicarbonate and
either citric acid, tartaric acid, or sodium biphosphate in
addition to the active ingredients. These powders may
be prepared also by adding small amounts of water to
the dry salts to obtain a workable mass.
 DENTIFRICES
o Dentifrices may be prepared in the form of a bulk
powder, generally containing a soap or detergent, mild
abrasive, and an anticariogenic agent.
 DOUCHES
o are completely soluble and are intended to be dissolved
in water prior to use as antiseptics or cleansing agents
for a body cavity. They most commonly are intended for
vaginal use, although they may be formulated for nasal,
otic, or ophthalmic use
 DUSTING POWDER
o are locally applied nontoxic preparations that are
intended to have no systemic action. They are applied to
various parts of the body as lubricants, protectives,
absorbents, antiseptics, antipruritics, anti-bromhidrosis
agents, astrin- gents, and antiperspirants.
 INSUFFLATIONS
o are finely divided powders that are intended to be
applied in the body cavities such as the ears, nose,
vagina, tooth socket, or throat. An insufflator (powder
blower) usually is employed to administer these
products.
 TRITURATIONS
o are dilutions of potent powdered drugs, prepared by
intimately mixing them with a suitable diluent in a
definite proportion by weight. The pharmacist sometimes
prepares triturations of poisonous substances in a
convenient concentration using lactose as the diluent,
for use at the prescription counter
DIVIDING POWDERS

PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES 1 of 16

 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
o Divided powders (chartula or chartulae) are dispensed
in the form of individual doses and generally are
dispensed in papers, properly folded. They also may be
dispensed in metal foil, small heat-sealed plastic bags,
or other containers.
o After a powder has been properly blended (using the
geometric dilution method for potent substances), it may
be divided into individual dosing units based on the
amount to be taken or used at a single time.
 Dividing powders, Folding Powders, Packaging Divided
powders
 DIVIDING POWDERS
o The ingredients must be precisely split into the required
number of doses after being weighed, minced, and
combined. Each dose should be precisely weighed and
put to a powder paper in order to maintain precision
throughout the preparation. The powder papers are
folded after this phase is finished.
 FOLDING POWDERS
o To ensure uniformity when the powders are eventually
put in the box for dispensing, care in forming the several
folds and practice are required. Powders of varied
height will arise from deviation from any of the three
main folds, and variations in the folded ends will also be
apparent when the powders are placed side by side.
Packaging and Divided Powders
1. Vegetable parchment, a thin, semi opaque, moisture-
resistant paper.
 WHEN A LIMITED BARRIER AGAINST MOISTURE IS
NECESSARY
2. White bond, an opaque paper with no moisture-resistant
properties.
 WHEN NEITHER VOLATILE NOR INGREDIENTS ARE
ADVERSELY AFFECTED BY AIR/MOISTURE
3. Glassine, a glazed, transparent, moisture-resistant
 WHEN LIMITED BARRIER AGAINST MOISTURE IS
NECESSARY
 VOLATILE MATERIALS
4. Waxed, a transparent waterproof paper.
 HYGROSCOPIC OR DELIQUESCENT PAPER
 VOLATILE MATERIALS
Size Classifications
1. SIEVING
 one of the simplest and probably most frequently used
methods
 particles of a powder mass are placed on a screen
made of uniform apertures
2. WET SCREENING
 The addition of water employed to dissolve any
unwanted binders and to reduce surface forces-
particularly in micromesh sieves- that oppose the flow
of particles through the sieve
3. SEDIMENTATION
 settling of particles in a liquid of a relatively low density,
under the influence of a gravitational or centrifugal field.
4. ELUTRIATION
 The particles are suspended in a moving fluid.
generally water or air.
5. FELVATION
 is a sieving along with a process that combines
elutriation and iodized bed to achieve parting fluid flow
rate and a turbulent fluid iodized within the felvation
separation.
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
Technologies, Machines & Methods Used in the
Production of Powders
Technologies
1. Intermediate and Fine Grinding Mills
Combination of three actions: Attrition, Rolling and Impact
 Attrition. This involves breaking down of the material
by a rubbing action between two surfaces.
 Rolling. This uses a heavy rolling member to crush
and pulverize the material.
 Impact. This involves the operation of hammers or
bars) at high speeds.
2. Roller Mills
 Roller mills in their basic form consist of two rollers revolving
in the same direction at different rates of speed.
 provides particle-size reduction mainly through compression
(crushing) and shear
 is quite versatile and can be used to crush a variety of
materials
3. Hammer Mills
 Consist of a rotating shaft on which are mounted either rigid or
swing hammers (beaters).
 These mills operate at high speed and generally with
controlled feed rate.
 Both impact and attrition provide the grinding action.
4. Centrifugal-Impact Mills
 are useful in reducing the particle size of fibrous material and
act by a combined cutting and shearing action.
 They consist of a horizontal rotor into which is set a series of
knives or blades.
5. Attrition Mills
 Attrition mills make use of two stone or steel grinding plates,
one or both of which revolve to provide grinding mainly
through attrition.
 These mills are most suit- able for friable or medium-hard,
free-flowing material.
6. Chaser Mills
 Chaser mills are so called because two heavy granite stones,
or chasers, mounted vertically like wheels and connected by a
short horizontal shaft, are made to revolve or chase each
other upon a granite base surrounded by a curb.
7. Pebble or Ball Mills
 Also called pot mills or jar mills, are operated on the principle
of attrition and impact.
 The grinding is affected by placing the substance in jars or
cylindrical vessels that are lined with porcelain or a similar
hard substance and containing pebbles or balls of flint,
porcelain, steel, or stainless steel.
8. Fluid-Energy Mills
 are used for pulverizing and classifying extremely small
particles of many materials.
 The mills have no moving parts, grinding being achieved by
subjecting the solid material to streams of high-velocity elastic
fluids, usually air, steam, or an inert gas.
9. Centrifugal-Impact Pulverizers
 This also has been found to be effective for the reduction of
the particle size of a wide variety of materials ranging from
very soft, organic chemicals to hard, abrasive minerals.
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 In addition, this type of mill is suited well for the size reduction
of heat-sensitive substances.
Machines and Methods
Manually
 When two or more powdered substances are to be combined
to form a uniform mixture, it is best to reduce the particle size
of each powder individually before weighing and blending.
 Depending on the nature of the ingredients, the amount of
powder, and the equipment, powders may be blended by:
I. Spatulation - blending small amounts of powders by
movement of spatula through them on a sheet of paper
or ointment tile. It is not suitable for large quantities of
powders or for powders containing potent substances,
because homogeneous blending is not as certain as
other methods.
II. Trituration - may be employed both to comminute and to mix
powders. If simple admixture is desired without the special
need for comminution, the glass mortar is usually preferred.
 Geometric Dilution - when a small amount of a potent
substance is to be mixed with a large amount of diluent this
method is used to ensure the uniform distribution of the potent
drug. This method is especially indicated when the potent
substance and other ingredients are the same color and a
visible sign of mixing is lacking.
 tumbling the powder in a rotating chamber. Special small-
scale and large-scale motorized powder blenders mix
powders by tumbling them.
o Mixing by this process is thorough but time
consuming. Such blenders are widely employed in
industry, as are mixers that use motorized blades to
blend powders in a large vessel.
Mechanical
a. V-Blender - This method involves tumbling the powders in a
rotating chamber designed to enhance the mixing process.
Mixing by this process is thorough but can be time
consuming; however, it can be done while performing other
duties. The speed of the rotating chamber is such that the
powders "tumble" over and over and do not simply slide down
the side of the chamber. This type of blender is very widely
used in industry on a large scale.
b. Triple V-Type Blender - This V-blender consists of three
individual chambers attached to the blender power unit and
allows up to three different blending processes to be
conducted simultaneously.
c. Turbula Mixer - This blender is used to obtain a
homogeneous mixing of powders with different specific
weights and particle sizes. The powders can be mixed in their
own closed container.
The Three Primary Mechanisms of Segregation of Powders:
Percolation
 can result from gravity causing small particles to move into
voids between larger particles, because of large particle size
differences.
Vibration
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
 causes small particles to move under the larger particles that
are pushed to the surface and result in separation of
differently sized particles.
Transportation
 particle beds with the constant acceleration and deceleration
results in separation. Similar changes occur when powders
are poured in a pile. The heavier particles will roll to the
outside, whereas the smaller particles located in the center of
the powder pile.
Small-Scale Mixing Equipment
 The pharmacist most generally employs the mortar and pestle
for the small-scale mixing usually required for prescription
compounding.
 However, spatulas and sieves also may be used on occasion.
The mortar and pestle method combines comminution and
mixing in a single operation. T
 hus, it is particularly useful where some degree of particle-size
reduction as well as mixing is required, as in the case of
mixtures of crystalline material.
 The blending of powders with a spatula on a tile or paper, or
spatulation, is used sometimes for small quantities of
powders, often as an auxiliary blending technique or when the
compaction produced by the mortar and pestle technique is
undesirable
Spatulation
 is a relatively inefficient method of mixing, thus principles of
geometric dilution must be employed.
 rarely used to prepare a finished dosage form.
 Sieving, usually is employed as a pre- or post-mixing
method to reduce loosely held agglomerates and to
increase the overall effectiveness of a blending process.
Large-Scale Mixing Equipment
The ideal mixer should produce a complete blend rapidly with as
gentle as possible a mixing action to avoid product damage. It
should be cleaned and discharged easily, be dust-tight, and
require low maintenance and low power consumption. All of these
assets are generally not found in any single piece of equipment,
thus requiring some compromise in the selection of a mixer.
I. Rotating-Shell Mixers
 The drum-type, cubical-shaped, double-cone, and twin-shell
blenders are all examples of this class of mixers. Drum-type
blenders, with their axis of rotation horizontal to the center of
the drum, are used quite commonly. These, however, suffer
from poor cross flow along the axis. The addition of baffles or
inclining the drum on its axis increases crossflow and
improves the mixing action.
II. Cubical and Polyhedron-Shaped Blenders
 With the rotating axis set at various angles also are
available
 However, in the latter, because of their flat surfaces, the
powder is subjected more to a sliding than a rolling
action, a motion that is not conductive to the most
efficient mixing.
III. The Cross-Flow blender
 Is an example of a twin-shell blender. The uneven length
of each shell in this blender provides additional mixing
action when the powder bed recombines during each
revolution of the blender.
IV. Fixed-Shell Mixers
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 The ribbon mixer, one of the oldest mechanical solid-
solid blending devices, exemplifies this type of mixer. It
consists of a relatively long troughlike shell with a
semicircular bottom.
V. Sigma-Blade and Planetary Paddle Mixers
 Are also used for solid-solid blending, although most
generally as a step prior to the introduction of liquids,
Mixers with high-speed impeller blades set into the
bottom of a vertical or cylindrical shell have been shown
to be very efficient blenders.
VI. Vertical Impeller Mixers
 Have the advantage of requiring little floor space, employ
a screw-type impeller that constantly overturns the batch.
The fluidized mixer is a modification of a vertical impeller
type.
VII. Motionless Mixers
 These are in-line continuous processing devices with no
moving parts. They consist of a series of fixed flow-
twisting or flow-splitting elements.
New Designs of Powder Formulation
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
Tablets
Tablets
 Tablets are solid dosage forms usually prepared with the aid
of suitable pharmaceutical excipients.
 Prepared primarily by compression, with a limited number
prepared by molding.
 Some tablets are scored, or grooved, which allows them to be
easily broken into two or more parts.
Advantages
 Unit dose form and offer greatest capabilities of all oral
dosage forms for greatest dose precision and the least
content variability.
 Cost is lowest of all dosage forms
 Lightest and most compact
 Easiest and cheapest to package and ship
 Product identification is the simplest and cheapest,
requires no additional processing steps when employing
an embossed or monogrammed punch face.
 Provide greatest ease of swallowing and least tendency of
“hang-up” above the stomach.
 They lend themselves to certain special-release profile
products (enteric or delayed-release tablets)
 Better suited to large-scale production
 Have the Best combined properties of chemical,
mechanical and microbiological stability.
Disadvantages
 Some drugs resist compression into dense compacts, owing
to their amorphous nature or flocculent, low-density
character.
 Drugs with poor wetting, slow dissolution properties,
intermediate to large dosages, opti- mum absorption high in
the gastrointestinal tract, or any combination of these
features may be difficult or impossible to formulate and
manufacture as a tablet that will still provide ade- quate or
full drug bioavailability.
 Bitter-tasting drugs, drugs with an objec- tionable odor, or
drugs that are sensitive to oxy- gen or atmospheric moisture
may require encapsulation or entrapment prior to
compression (if feasible or practical), or the tablets may
require coating. In such cases, the capsule may offer the
best and lowest cost approach.
Properties
A tablet
(1) should be an elegant product having its own identity while
being free of defects such as chips, cracks, discoloration,
contamination, and the like;
(2) should have the strength, to withstand the rigors of mechanical
shocks encountered in its production, packaging, ship- ping, and
dispensing; and
(3) should have the chemical and physical stability to maintain its
physical attributes overtime. Pharmaceutical scientists now
understand that various physical properties of tablets can undergo
change under environmental or stress conditions, and that physical
stability, through its effect on bioavailability in particular, can be of
more significance and concern in some tablet systems than
chemical stability.
Classification of Tablets
Compressed Tablets or Standard Compressed Tablets
 This category refers to stan- dard uncoated tablets made by
compression and employing any of the three basic methods of
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
manufacture: wet granulation, double compac- tion, or direct
compression.
 Compressed tablets usually contain a number of
pharmaceutical excipients:
1. Diluents and fillers - add necessary bulk
2. Binders and adhesives - promote adhesion and
maintain integrity of final tablet
3. Disintegrants or disintegrating agents - promote
breakup of the tablets after administration
4. Antiadherents, glidants, lubricants,
lubricating agents - enhance flow
5. Miscellaneous adjuncts - colorants and flavorants.
Multiple Compressed Tablets
 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.
 Layered Tablets - 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.
 Tablets within tablets - special machines are
required to place the preformed core tablet precisely
within the die for application of surrounding fill
material.
Sugar Coated Tablets
 Compressed tablets may be coated with a colored or an
uncolored sugar layer. The coating is water soluble and
quickly dissolves after swallowing.
 Sugarcoat protects the enclosed drug from the
environment and provides a barrier to objectionable taste
or odor.
 The sugarcoat also enhances the appearance of the
compressed tablet and permits imprinting of identifying
manufacturer's information.
Film Coated Tablets
 Film-coated tablets are compressed tablets coated with a
thin layer of a polymer capable of forming a skin-like
film.
Gelatin Coated Tablets
 The gelatin coating facilitates swallowing, and gelatin-
coated tablets are more tamper evident than unsealed
capsules.
Delayed Action Tablets
 This tablet is intended to release a drug after some time
delay, or after the tablet has passed through one part of
the GI tract into another.
Chewable Tablets
 These tablets are intended to be chewed in the mouth
prior to swallowing and are not intended to be swallowed
intact.
 The purpose is to provide a unit dosage form of
medication which can be easily administered to infants
and children or elderly.
 The most common chewable tablet is an aspirin tablet
intended for use in children.
 Many antacid tablet products are of the chewable type.
 Examples include Pepcid AC chewable tablets (J&J
Merck) and
 Rolaids chewable tablets (Pfizer Consumer Healthcare).
Buccal and Sublingual Tablets
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
 Intended to be held in the mouth and release drug
contents for absorption through the oral mucosa.
 Small and flat
 Held between the cheek and teeth or cheek pouch, or
beneath the tongue.
 Should be formulated with bland excipients, which do not
stimulate salivation.
Troches and Lozenges
or  Intended to exert a local effect in the mouth or throat.
 Commonly used in sore throat or to control coughing in
the common cold.
 May contain local anesthetics, various antiseptic and
antibacterial agents, demulcents, astringents and
antitussives.
 Designed not to disintegrate in the mouth but to dissolve
or slowly erode over a period of 30 min or less.
Dental Cones
 Minor tablet form that are designed to be placed in the
empty socket remaining following a tooth extraction
 Prevent multiplication of bacteria
Implantation Tablets
 Designed for subcutaneous implantation in animals or
man.
 Provide prolonged drug effects (1 month to a year)
 Provide as constant a drug delivery release rate as
possible.
 Small, cylindric, or rosette-shaped forms and not more
than 8 mm in length.
Vaginal Tablets
 Undergo slow dissolution and drug release
 Ovoid or pear-shaped for retention in the vagina
 Often buffered to promote pH favorable to the action of a
given antiseptic agent
 Should be designed to be compatible with some type of
plastic tube inserter, which is employed to place the
tablet in the upper region of vagina
Effervescent Tablets
 Designed to produce a solution rapidly with the
simultaneous release of carbon dioxide.
 Typically prepared by compressing the active ingredients
with mixtures of organic acids (citric acid or tartaric acid)
Dispensing Tablets
 Intended to be added to a given volume of water by the
pharmacist or consumer, to produce a solution of a given
drug concentration.
 Must typically comprise totally soluble components.
Hypodermic Tablets
 Composed of one or more drugs with other readily water-
soluble ingredients and are intended to be added to
sterile water or water for injection
Tablet Triturates
 They are small, usually cylindric, molded, or compressed
tablets.
 Rarely used today
 The drugs employed in such products were usually quite
potent and were mixed with lactose and possibly a
binder, such as powdered acacia, after which the mixture
was moistened to produce a moldable, compactable
mass.
Tablet ingredients
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 Tablet contain a number of inert materials
 They may be classified according to the part they play in the
finished table
 Diluents
 Increase bulk to make tablet a practical size for
compression - diluents used for this purpose include
dicalcium phosphate, calcium sulfate, lactose, cellulose,
kaolin, mannitol, sodium chloride, dry starch, and
powdered sugar.
 Used as excipients for direct compression formulas have
been subjected to prior processing to give them flowability
and compressibility.
 Binders
 Agents used to impart cohesive qualities to the powdered
material are referred to as binders or granulators.
 impart cohesiveness and ensure the tablet remains intact
after compression and improve free-flowing qualities by
the formulation of granules of desired hardness and size.
 Materials commonly used as binders include starch,
gelatin and sugars such as sucrose, glucose, dextrose,
molasses and lactose
 Binders are used both as a solution and in dry form,
depending on the other ingredients in the formulation and
the method of preparation.
 STARCH PASTE - used widely as a binder
 GELATIN SOLUTION - used as a 10-20%
solution; gelatin solutions should be prepared
freshly as needed and used while warm or they
will solidify.
 CELLULOSIC SOLUTION - hydroxypropyl
methylcellulose (HPMC) has been widely used.
 POLYVINYLPYRROLIDONE - PVP can be used
as an aqueous or alcoholic solution, and this
versatility has increased its popularity.
Concentrations range from 2% and vary
considerably.
 Most binders used in solutions are polymeric.
 Lubricants
 Prevent adhesion of the tablet material to the surface of
the dies and punches, reduce interparticle friction,
facilitate the ejection of th tablets from the die cavity, and
may improve rate of flow of the tablet granulation
 The addition of proper lubricant is highly desirable if the
material to be tableted tends to stick to the punches and
dies.
 In selecting a lubricant, proper attention must be given to
its compatibility with the drug agent
 Glidants
 Improves the flow characteristics of a powder mixture.
 always added in the dry state just prior to compression
 Colloidal silicon dioxide Cab-o-sil (Cabot) is the most
commonly used glidant and generally used in low
concentrations of 1% or less.
 Disintegrants
 Facilitate its breakup or disintegration after administration
 The oldest and still the most popular disintegrants are
corn and potato starch that have been well dried and
powdered.
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
 Coloring Agents
 Color helps the manufacturer to control the product during
its preparation, as well as serving as a means of
identification to the user.
 Most common method of adding color to a tablet
formulation is to dissolve the dye in the binding solution
prior to the granulation process.
 Flavoring Agents
 Aspartame (Pfizer) is one of the new natural sweeteners
being sought.
 Sweeteners other than the sugars have the advantage of
reducing the bulk volume, considering the quantity of
sucrose required to produce the same degree of
sweetness.
 Do not affect the physical characteristics of the tablet
granulation.
Processing Problems
Due to Tableting Process
Capping and Lamination
 Capping is a term used to describe the partial or complete
separation of the top or bottom crowns of a tablet from the
main body of the tablet.
 Lamination is the separation of a tablet into two or more
distinct layers.
Due to excipients
Picking
 "Picking" is a term used to describe the surface material
from a tab- let that is sticking to and being removed from
the tablet's surface by a punch.
 Picking is of particular concern when punch tips have
engraving or embossing.
o Small enclosed areas such as those found in the
letters "B," "A," and "O" are difficult to
manufacture cleanly. Tablet materials that stick
to the punches can accumulate to the point of
obliterating the tip design.
Chipping
 removal of a small portion of tablet edges
Sticking
 "Sticking" refers to tablet material adhering to the die
wall.
 When sticking occurs, additional force is required to
overcome the friction between the tablet and the die wall
during ejection.
 Serious sticking at ejection can cause chipping of a
tablet's edges and can produce a rough edge.
Due to Machines
Double Impression
 This involves only punches that have a monogram or
other engraving on them. At the moment of compression,
the tablet receives the imprint of the punch.
Due to One Factor
Mottling
 Mottling is an unequal distribution of color on a tablet,
with light or dark areas standing out in an otherwise
uniform surface.
 One cause of mottling is a drug whose color differs from
the tablet excipients or a drug whose degradation
products are colored.
Technologies, Machines, & Method Used in the
Production of Powders
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
1. Granulation Methods
a. Wet Granulation
 Wet granulation is a widely employed method for the
production of compressed-tablets. 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, and
(g) forming tablets by compression.
b. Fluid Bed Granulation
 The concept was to spray a granulating solution onto the
suspended particles, which then would be dried rapidly in the
suspending air.
 The main benefit from this system is the rapid granulation and
drying of a batch.
 The two main firms that developed this technology are Glatt
and Aeromatic (now NIRO). The design of these systems is
basically the same with both companies. In this method,
particles of an inert material or the active drug are suspended
in a vertical column with a rising air stream; while the particles
are suspended, the common granulating materials in solution
are sprayed into the column.
 There is a gradual particle buildup under a controlled set of
conditions resulting in a tablet granulation that is ready for
compression after the addition of the lubricant.
 An obvious advantage exists, since granulating and drying
can take place in a single piece of equipment. It should be
noted, however, that many of the mixers discussed previously
can be supplied with a steam jacket and vacuum and can
provide the same advantage.
c. Dry Granulation
 By the dry granulation method, the powder mixture is
compacted in large pieces and subsequently broken
down or sized into granule. For this method, either the
active ingredient or the diluent must have cohesive
properties. Dry granulation is especially applicable to
materials that cannot be prepared by wet granulation
because they degrade in moisture or the elevated
temperatures required for drying the granules.
 Slugging
 After weighing and mixing the ingredients,
the powder mixture is slugged, or
compressed, into large flat tablets or pellets
about 1 inch in diameter. The slugs are
broken up by hand or 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.
 Roller Compaction
 Instead of slugging, powder compactors may
be used to increase the density of a powder
by pressing it between rollers at 1 to 6 tons
of pressure. The compacted material is
broken up, sized, and lubricated, and tablets
are prepared by compression in the usual
manner. The roller compac- tion method is
often preferred to slugging. Binding agents
used in roller compaction formulations
include methylcellulose or hydroxy
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
methylcellulose (6% to 12%), which can
produce good tablet hardness and friability.
d. Direct Compression
 Some granular chemicals, like potassium chloride,
possess free-flowing and cohesive properties that enable
them to be compressed directly in a tablet machine
without any need of granulation.
 For chemicals lacking this quality, special
pharmaceutical excipients may be used to impart the
necessary qualities for the production of tablets by direct
compression.
 These 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 carboxymethyl cellulose fibers, and cross-
linked PVP; lubricants, such as magnesium stearate and
talc; and glidants, such as fumed silicon dioxide.
 Tablet Dedusting
o To remove traces of loose powder adhering to
tablets following compression, the tablets are
conveyed directly from the tableting machine to a
deduster. The compressed tablets may then be
coated.
Methods: Related Granulation Process
Spheronization
 A form of pelletization, refers to the formation of spherical
particles from wet granulation. Particles are round, they
have good flow properties when dried.
 They can be formulated to contain sufficient binder to
imparts cohesiveness for tablet
 Advantage :production of granules ,regular in shape ,size
and surface characteristics ,ability to regulate the size of
the sphere within a narrow particles size distribution
Spray-drying
 A number of tableting additives suitable for direct
compression have been prepared by the drying process
known as spray-drying.
 The method consists of bringing together a highly
dispersed liquid and a sufficient volume of hot air to
produce evaporation and drying of liquid droplets
Spray-congealing
 Also called Spray-chilling. A technique similar to spray-
drying.Consists of melting solids and reducing them to
beads or powder by spraying the molten feed into a
stream air or other gas. Ambient or cooled air is used as
basic equipment ,no source of heat is required.
Tablet Coating
Tablet Coating Principles
1. to mask the taste ,odor,or color of the drug
2. provide physical and chemical protection for the drug
3. control the release of the drug from the tablet
4. protect the drug from the gastric environment of the
stomach with an acid-resistant enteric coating
5. incorporate another drug or formula adjuvant in the
coating to avoid chemical incompatibilities or to provide
sequential drug release
6. improve the pharmaceutical elegance by use of special
colors and contrasting printing
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
Sugar Coating
1. Sealing
 prevent moisture penetration into the tablet core especially
needed in pad-ladling processes , in which localized
overwetting of a portion of the tablet bed occurs.
2. Subcoating
 Is applied to round the edges and build up the tablet
size.
3. Syruping
 Purpose: to cover and fill in the imperfections in the tablet
surface caused by the subcoating steps , and to impart the
desired color to the tablet.
4. Finishing
 To attain final smoothness and the appropriate color to the
tablets, several coats of a thin syrup containing the desired
colorant are applied in the usual manner.
5. Polishing
 The tablets can be polished in clean standard coating pans, or
canvas-lined polishing pans , by carefully applying powdered
wax or warm solutions of these waxes in naphtha or other
suitable volatile solvents
Film Coating
1. A film former -capable of producing smooth, thin films
reproducible under conventional coating conditions and
applicable to a variety of tablet shapes.
o Example: cellulose acetate phthalate
2. Alloying substance- providing water solubility or permeability
to the film to ensure penetration by body fluids.
o Example: polyethylene glycol
3. Plasticizer - to produce flexibility and elasticity of the coating
and thus provide durability
o Example: castor oil
4. Surfactant- to enhance spreadability of the film during
application.
o Examples: polyoxyethylene sorbitan derivatives
5. Opaquants and colorants - to make the appearance of the
coated tablets handsome and distinctive.
o Examples: titanium dioxide, FD&C or D&C dyes
6. Sweeteners, flavors, and aromas- enhance the acceptability
of the tablet by the patient.
o Example: sweeteners, saccharin
7. Glossant - provide luster to the tablets without a separate
polishing operation.
o Example: beeswax
8. Volatile solvent- to allow the spread of the other components
over the tablets while allowing rapid evaporation to permit an
effective yet speedy operation.
o Example: alcohol mixed with acetone
Film Coating Problems
Picking and Sticking
 overwetting or excessive film tackiness causes tablets to
stick to each other
Roughness
 gritty surface is a defect often observed
Orange -Peel Effect
 Inadequate spreading of the coating solution before
drying causes a bumpy or orange peel effect
Bridging and Filling
 Film may shrink and pull away from the sharp corner
Blistering
 Too rapid evaporation of the solvent from the core and
effect of high temp may result in blistering
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
Hazing/Dull film
 aka bloom. Occur when too high processing temp. is
used for a particular formulation
Color variation
 Cause: Improper mixing, uneven spray pattern and
insufficient coating
Cracking
 Occurs if internal stresses in the film exceed the tensile
strength of the fil
Modified Release Film Coating
 These tablets are designed in such a way that the active
ingredients' rate of release is modified or altered.
 2 types of Modified release dosage form:
o Extended-release, two fold reduction in dosing
frequency, often called sustained-release or
controlled-release dosage forms and
o Delayed-release: one that releases active
ingredients at some time other than promptly after
administration
Enteric Coating
 are intended to pass through the stomach intact to
disintegrate and release their drug content from
absorption along the intestine
Fluid Bed or Air Suspension Coating
 also termed fluidised bed processing or spray coating, is
accomplished by suspending solid particles of core
material in an upward-moving stream of air, which may
be heated or cooled
Compression Coating
 Is a system in which the entire surface of an inner core is
surrounded by the coat.This coat prevents the drug
release from the core until the drug coat is entirely
dissolved or removed.
Technologies and Machines
Basic Component of Tablet Compression Machine
1. Hopper(s) for holding & feeding granulation to be
compressed
2. Dies that define the size & shape of the tablets
3. Punches for compressing the granulation within the dies
4. Cam track for guiding the movement of the punches
5. A feeding mechanism for moving granulation from the
hopper into the dies
The compression cycle of a single punch
FILLING: upper punch is withdrawn from the die by the upper cam.
Lower punch is lowered in the die so powder falls in through the
hole and fills the die
METERING: lower punch moves up to adjust the powder weight. It
raises and expel some powder
COMPRESSING: Upper punch is driven into the die by upper cam
as both punches compress the powder
EJECTION: Upper punch is withdrawn by the upper cam.Lower
punch is pushed up to expel tablet
Tablet Machines
1. Single Punch Machine - simplest tableting machine
2. Rotary Tablet Machine - offer advantage because of
increasing production carry out number of sets of of
punches this method promotes a uniform fill of a die , an
accurate weight for the tablet
3. High Speed Rotary Tablet Machine - has evolved
gradually into models capable of compressing tablets at
high production
4. Multilayer Rotary Tablet Machine - -capable of
producing multiple layer tablets
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
C. Tablet Coating Machines -Mothes and Dublanc, two Frenchmen, are generally credited
1. Standard coating pans with the invention of the gelatin capsules.
 consists of a circular metal pan mounted somewhat -used in clinical trials.
angular on a stand
 Pan is 8-60 inch in diameter and is rotated on its Advantages Disadvantages
horizontal axis by motor
 Heated air is supplied by inlet air supply Ease of use not used for extremely soluble
 Exhaust by the means of of duct materials
 Coating solutions are applied to the tablets by ladling or
spraying. portability not used for highly efflorescent or
2. Perforated coating pans deliquescent materials
 In general, all equipment of this type consists of a
Mask unpleasant taste HGC can be tampered
perforated or partially perforated drum that is rotated in
and odor of drug
an enclosed housing.
 In the Accela-Cota and Hi-coater system, drying air is i. Types of Capsules
directed into the drum , is passed through the tablet bed 1. Hard Gelatin Capsule
 Driacoater introduces drying air through hollow -also referred to as the dry-filled capsule (DFC)
perforated ribs located on the inside periphery of the -consist of two sections, the longer body which contains the drug,
drum and the cap which slips on with the body
 As the coating pans rotates into the tablet bed, drying air Sizes of Capsule
passes up through and fluidized the tablet bed.
 Exhaust is from the back of the pan
3. Glat Coater pans
 Drying air can be directed from inside the drum through
the tablet bed and out an exhaust duct
 With an optional split-chamber plenum , drying air can be
directed in the reverse manner up through the drum
perforations for partial fluidization of the tablet bed
4.Fluidized Bed Coater
 are also highly efficient drying systems, the tablet mass -For human use, empty capsules ranging in size from 000 (the
is achieved in a columnar chamber by the upward flow of largest) to 5 (the smallest) are commercially available.
drying air, airflow is controlled so that more airs enters -For veterinary use: No.s 10, 11and 12 having capacities of 30, 15
the center column and 7.5 g, respectively
D. .New Design of Tablet Formulation
Tablets made by electrostatic deposition
 In this technology, coating powders, containing coating Materials
polymers, pigments, and other excipients, are directly HGC are made largely from
sprayed onto the surface of the solid dosage forms
 Gelatin
through an electrostatic gun without using any organic
solvent or water. The deposited coating powders are
o Heterogeneous product derived by irreversible
further cured to form a coating film. hydrolytic extraction of treated animal collages
Three-dimensional printing of tablets such, it never occurs naturally
o Common sources:
 Quite similar to ink-jet printer technology. To this date
there are no commercial tablets made from this  Animal bones
technology  Hide portions
Web-coated system  Frozen pork skin
 Sheets of a substrate were coated with drug and binder  sugar
solution. A number of sheets then laminated or glued  Water
together. Due to impracticality it was abandoned in the  FD&C colorant
mids-1980
Hot melt extrusion  opacifying agent (titanium oxide)
 Has been used as a processing technique in the plastic  Preservatives
industry. Process involves the active, suitable polymer o The USP 0.15% sulfur dioxide to prevent
carrier, and other excipients being mixed in the molten decomposition during manufacture
state and then extruded through a die TWO TYPES OF GELATIN
Type A
CAPSULES - mainly derived from pork skins by acid processing
-exhibits an isoelectirc point in the region of pH 9
Capsule Type B
-solid dosage forms in which medicinal agents and inert - obtained from bones and animal skins by alkaline process (base)
substances are enclosed in a small gelatin shell. -has its isoelectric zone in the region of pH 4.7
METHODS OF PREPARATION OF CAPSULE

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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
Pin Method
-formed by dipping cool stainless steel mold pins into a gelatin
solution
-one used in large-scale commercial production.
Centrifugal Casting
2. Soft Gelatin Capsule
-made of gelatin to which glycerin or polyhydric alcohol such as
sorbitol has been added.
-contains more moisture than hard capsules
-used to encapsulate and hermetically seal liquids, suspensions,
pasty materials, dry powders, and even performed tablets
3. Microencapsulation
-process or technique by which thin coatings can be applied
reproducibly to small particles of solid, droplets of liquid, or
dispersions, thus forming microcapsules
-provides the means of converting liquid to solids, of altering
colloidal and surface properties, of providing environmental
protection, and of controlling the release characteristics or
availability of coated materials.
MATERIALS:
 Core Material
o the specific material to be coated, can be liquid
or solid in nature.
 Coating Material
o selection of a specific coating materials from a
lengthy list of candidate materials presents the
following question to be considered:
 What are the specific dosage or
product requirements?
 What coating materials will satisfy the
product objectives and requirements?
 What microencapsulation method is
best suited to accomplish the coated
product objective?
Technologies, Machines & Methods
i. Hard Gelatin Capsule
Method of Production
1. Pin Method
a. Dipping-pins are dipped into a gelatin sol of carefully
controlled viscosity to form caps and bodies
b. Spinning-the pins are usually rotated to distribute the
gelatin uniformly
c. Drying-the pins are moved through a series of controlled
air drying kilns for the gradual and precisely controlled
removal of water
d. Stripping-capsules are stripped from the pins by bronze
jaws
e. Trimming-trimmed to length by stationary knives while
the capsule are being spun in chucks or collets
f. Joining- the cap and the body are joined and ejected
from the machine
2. Centrifugal Casting
Three Major Supplier of Empty Capsule
a. Eli Lily and Company, Indianapolis, IN
b. Capsugel, Greenwood, Sc;
c. the R.P. Scherer Corporation, Troy, M
Conditions:
 Empty capsules as usually received range in moisture content
between 12% and 15%
 Below 10% moisture content, they become brittle and shrink
to the point of not fitting into the filling equipment
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
 Above 16% moisture content, they may cause size problems
in the filling equipment, plus a loss of mechanical strength
 Exposure to either heat or moisture extremes can distort
empty capsules to the extent that cannot be handled by
automatic filling equipment
Extemporaneous Filing Methods
The process of working:
a. Rectification
 The empty capsules are oriented so that all point the
same direction i.e. body end downwards
 In general, capsule pass one at a time through a channel
just wide enough to provide grip at cap end
 The capsules will always be aligned body end
downwards, regardless of which end entered the channel
first with the help of specially designed blades
b. Separating the caps from empty capsules
 The rectified capsules are delivered body end first into
the upper portion of split bushings or split filling rings
 A vacuum applied from below pulls the body down into
the lower portion of the split bushing
 The diameter of the bush is too large to allow them to
follow body
 The split bushings are separated to expose the bodies for
filling
c. Filling the bodies
 Direct Method
o The Punch Method
 Powder is placed on a sheet of a clean paper
or porcelain plate.
 It is formed into a cake having a depth of
approximately one-fourth to one-third the
length of the capsule body.
 Then the empty capsule body is held
between the thumb and forefinger and
punched vertically into the powder cake
repeatedly until filled.
o Feton Capsule Filling
 with empty capsule in the loader tray, the
tray placed on top of the filler unit
 the loader inserts the capsules into the filling
unit and is removed, and the top plate is
lifted to separate the caps from the bodies
 the powder is placed on the unit and the
capsule bodies filled
 the top plate is returned to the unit and the
caps placed on filled capsule bodies
 Indirect Filling Method
o Vibratory Fill Principle
 In the powder, a perforated resin plate is
positioned and connected to a vibrator
 The powder blend tends to be fluidized by
the vibration of plate and assists the powder
to flow into the bodies through the holes in
resin plate
o Piston Tamp Principle
 In this pistons or tamping pins lightly
compress the individual doses of the
powders into plugs( also called as slugs) and
eject the plugs into empty capsule bodies
10 of
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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 DOSING DISC PRINCIPLE: A solid ‘stop’ o the machine is specifically designed to fill
brass plate is sliding down the dosing disc to pellets.
close off the hole. Five sets of pistons o uses a rotary rectification system which orients
compress the powder into cavities to form the capsules into a turret.
plugs o the machine is rated as filling 1200 capsules per
 DOSATOR PRINCIPLE: It consists of a cylindrical minute.
dosing tube fitted with a movable piston. The position of 2. Farmatic
the piston is preset to a particular height to define a  the machine features continuous motion with dosator-
volume. Powder enters the open end of dosator and is
type powder feeding units and is totally enclosed for dust
slightly compressed against the piston into a plug
and noise control
 Filling of Pellets  Totally enclosed for dust and noise control
o Double Slide Method
 Adjustable vacuum for separating the capsules after
 Pellets flow from pellet magazine to dosing rectification
chambers
 Dosing slide is closed to separate dosing  Product hopper: powder is moved by a screw conveyor to
the operating tower.
chamber and pellet magazine
 Outlet slides open  Dosators
o Vacuum-Assisted Method o Powder slug is ejected into the capsule body, after
which the capsule is closed.
 Dosing tube enters pellet bed
 With the help of vacuum, the pellets are  Digital display
sucked into the dosing tube o indicates the status of the weight and
 Excess pellet are scraped off the end of compression.
the dosing tube  MODELS
 Dosing tube is lowered and pellets
released into capsule body Models Capacity
 Filling of Tablets
 Dosing slide which can accommodate exactly 1 2000/15 40,000 cap per hour
tablet moves underneath tablet feeder
 Slider moves over the capsule body where tablet 2000/30 80,000 cap per hour
simply drops into it
 If properly filled, the pin dropped into the capsule 2000/60 160,000 cap per hour
body will have limited movements, the horizontal bar
connected to the pin touches the sensor
 If not properly filled, the horizontal bar will switch the 3. Hofliger and Karg
sensor indicating incorrect filling. Empty capsules  the machine feature continuous motion with dosator type
can be detected and eliminated from the product. powder feeding units and are totally enclosed for dust
d. Scraping the excess powder and noise control
e. Replacing the caps  Dosators
f. Sealing the capsules o measure and deliver the powder as a slug to he
g. Cleaning the outside of the filled capsule capsules
o the powder slug is ejected into the capsule
Machine Filling Methods body, after which the capsule is closed.
Filling Equipment
1. Lilly/ Parke Davis  Empty capsule storage hopper: holds the empty
capsule shells.
 these capsule filling machines requires an individual
operator and may achieve daily output of up to 200,000  Rectifier: rectifies the capsules.
capsules  Faulty capsules are removed and checked by a vacuum
 In this equipment, the powder is filled to the supper system, which provides a signal upon feed interruption.
surface of the  Bulk powder storage hopper: holds the bulk powder
Model Filling Materials body- and delivers the following auger principle.
containing  Capsule body transport system: holds the separated
GFK- Capsules, Thixotropic ring, and the bodies and caps individually and transports to various
303 pellets, Liquid fill is therefore working stations.
and tablets primarily  Completely automatic and require only compressed air
GFK- volumetric and a power for operation.
602
 Minimum total fill weight are achieved with the highest turntable speed
 Maximum total fill weight are achieved at the lowest rotational speed
GFK-
 ROTOFIL
1500

GFK- Not included

2500 4. Macofar

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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 Macofar line of equipment consists of three models.  Screw feeder
 Low to medium capacity machines  High pressure air assisted bushing clean up.
 Similar method of rectification and filling. 8.Zanasi
 Separation accomplished by vacuum.  Nine different units in four model lines
 Follows dosator principle  LZ-64 : 4000 capsules per hour
 AZ-20 : 9000 TO 20000 capsules per hour
Model Capacity  BZ series
 BZ-40 : 30000/hr
MT-12 35,000 cap per hour  BZ-72 : 60000/hr
 BZ-110 : 110000/hr
MT13/ 5,000 cap per hour  BZ-150 : 150000/hr
1
 Z-5000 series
MT13/ 10,000 cap per hour  Z-5000-R1 : 70000/hr
2  Z-5000-R2 : 110000/hr
 Z-5000-R3 : 150000/hr
5. mG2
Filling Operations
 Five models of continuous motion filling machines are
Empty Capsule
offered by mG2.
 are sold by sizes; from size 000, the largest, to size 5 the
smallest.
Model Capacity  consideration should be given to techniques for handling and
storage of empty capsules in any production facility
G36/4 150 cap per minute Formulation
 General Problems:
G36/2 300 o Flow of the resultant mixture
o Physical incompatibilities
G36 600
 Specific Criteria for the choice of suitable diluents
G37N 1600 o The powder mix must provide the type of flow
characteristics required by the equipment:
G38 1000  Lily, Parke-Davis, Hofliger and Karg, Osaka and
Perry Machine= powder must be free flowing
o Zanasi, Macrofar, Farmatic, and mG2 equipment=
 Similar method of operation as macofar model. powder must have sufficient cohiseveness to retain
o G37 modified to G37N to its slug from during delivery to the capsule.
o continuous motion providing 2 ½ times the  Potential incompatibilities
filling rate of G36  Choice of excipients should be made with a view toward
o improved handling of empty capsules. current FDA regulations
o Lessened power dusting and noise reduction.  Current Regulatory Test:
o External adjustments of weight control and o Weight Variation
powder compression. o Content Uniformity
 G38 slightly slower than G37N o Containers for Dispensing Capsules
o Disintegration Test for Capsule
6. Osaka
o Solubility
 High capacity, continuous motion machine. o Dissociation Test for Capsule
 The only model available is o Content Labeling Requirements,
o R-180 : 70000 to 165000 capsules per hour o Stability testing
 Follows vibratory filling principle o Moisture Permeation test
 Two rows of capsule bodies Finishing
 External adjustment of fill weights  finished capsule require some sort of dusting and/ or
 Can be modified to 400,000 capsules per hour with some polishing operation before remaining operations of
auxiliary equipment. inspection, bottling, are completed
7. Perry  Pan polishing
 Model: CF ACCOFIL o the AccelaCota tablet coating pan may be used
 Capacity: 60000 capsules per hour to dust and polish capsules
 Capsules rectified into 24 vertical tubes
o Polyurethane or cheese cloth liner is placed in
the pan and liner is used to trap the removed
 Sensor system assisted rectification dust as well impart a gloss to the capsules

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 Pharmaceutical Lesson 3.2: Solid Dosage Form
Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 Cloth dusting  shellac,
o the bulk filled capsules are rubbed with a cloth  cellulose acetate phthalate
that may or may not be impregnated with an  certain resins
inert oil. Separation of Incompatible Materials
 Brushing  carried out by the use of a two-phase fill in the capsule;
o capsules are fed under rotating soft brushes  one phase consist of either a soft capsule, a smaller
which serve to remove the dust from the harder capsule, a pill, or a suitably coated tablet that is
capsules shell. filled into each capsule
o Machined Used:  Following the second phase, a powder is filed in the
 ROTOSORT usual manner.
 Erweka KEA dedusting and polishing Filling of Conventional two-piece gelatin capsules with liquid
machine and semisolid
 Seidenader Equipment
Special Techniques Soft Gelatin Capsule
Imprinting Methods
1. Plate Process
 convenient method by which company and or product
identification information can be placed upon each  the oldest commercial method of manufacture
capsule  A warm sheet of prepared gelatin is laid over the lower
 Imprinting operation is best performed on empty plate and the liquid is poured on it.
capsules.  A second sheet of gelatin is carefully put in place and
 Three Major Suppliers of Equipments: this is followed by the top plate of the mold.
o Harnett  The set is placed under the press where pressure is
 outputs as high as 500,000 capsules applied to form the capsule which is washed off with a
per hour; prints around the volatile solvent to remove any trace of oil from the
circumference of the capsule. exterior.
o Markem 2. Rotary-Die Process
 approximately 60,000 to 250,000  Liquid gelatin flowing from an overhead tank is formed
capsules per hour; allow for two sided into two continuous ribbons by the rotary die machine
printing but not circumferential and brought together between twin rotating dies.
o Ackley  At the same time, metered fill material is injected
 offers a straight line imprinter with an between the ribbons precisely at the moment that the
output rate of about 500,000 capsules dies form pockets of the gelatin ribbons.
per hour.  These pockets of fill-containing gelatin are sealed by
Sealing pressure and heat and then severed from the ribbon.
 Gelatin Banding  The capsule is washed with organic solvent and pre-dried
o seals with band of gelatin 3. Reciprocating Die Process(Norton Capsule Machine)
 Heat Welding  This continuous soft gelatin capsule processing
o fuses caps to body through double wall technology was developed by Norton Company in 1949.
thickness  This process is similar to the rotary process in that
 Thermal coupling ribbons of gelatin are formed and used to encapsulate
the fill, but it differs in the actual encapsulating process.
o uses liquid wetting agent to lower melting point
between cap and body then bods  The gelatin ribbons are fed between a set of vertical dies
that continually open and close to form rows of pockets in
 Snap-Fit and Coni-Snap
the gelatin ribbons.
o a pair of matched looking rings are formed into
 These pockets are filled with the medication and are
the cap and body portions of the capsule
sealed, shaped, and cut out of the film as they progress
through the machinery.
Special Purpose Capsule
 capsule to which special treatment has been given in an  As the capsules are cut from the ribbons, they fall into a
cooled solvent bath that prevents the capsules from
attempt to retard the solubility in some manner.
adhering to one another.
 Formalin Treatment 4. Accogel Capsule Machine
o employed to modify the solubility of gelatin  uses the method of rotary dies but is unique in that it is
capsules. the only machine that successfully can fill dry powder into
o results in an unpredictable decrease in soft gelatin capsules.
solubility of the gelatin film.  Extremely versatile, not only producing capsules with dry
 Various Coatings powder but also encapsulating liquids and combination of
o used in an effort to provide similarly modified liquids and powders
solubility characteristics 5. Seamless Process (Bubble Method/ Globex Method)
o Coating includes:  produces one-piece soft gelatin capsules without the use
 salol, of dies.

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Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 The process is often referred to as a bubble method that
creates seamless, spherical soft gelatin capsules called
pearl.
 In this process, a molten gelatin stream flows though the
outer nozzle of a concentric tube at a constant rate, and
the medicated liquid formulation is dispensed through the
inner orifice by means of a precision metering pump.
 The emerging stream is broken up into an intermittent but
steady flow of uniform-sized by a pulsating mechanism,
leading to the formation of droplets enveloped in molten
gelatin.
 The formed capsules are quickly removed from the
nozzle, slowly congealed, and automatically ejected from
the system.
i. Capsule Manufacture, Processing, and Control
I. Gelatin Preparation
 The manufacturing areas of a typical plant are air-
conditioned to assure the proper conditioning of the
gelatin films, the proper drying of the capsules, and the
consistent low moisture content of raw materials and
mixtures.
 Temperature is at 20 to 22 degree celsius and humidity is
40% in operating areas and 20-30% in drying areas
 gelatin is weighed in printomatic scale and chilled liquid
constituents in suitable equipment, such as Pony Mixer
 The mixing process requires about 25 min for 270 kg of
mass, and the melting procedure requires about 3 hours.
 The mass is then maintained at a temperature of 57 to
60°C before and during the encapsulation process
II. Material Preparation
 they have a weigh-off and mixing area
 Typical equipments used:
 Printomatic scales
 Stainless-steel jacketed tanks
 Mixer (Cowles)
III. Milling or Homogenized Process
 After the initial blending is completed, the mixture is put
through a milling or homogenizing process, using
equipment such as the homoloid mill, stone mill, hopper
mill, or the Urschel Comitrol.
 The purpose of the milling is to break up agglomerates
and to make certain that all solids are “wet” with the liquid
carrier
IV. Deaceration
 necessary to achieve uniform capsule fill weights
 It also protects against loss of potency through oxidation
prior to and during capsulation.
 Most liquids and suspensions may be deaerated by
means of equipment designed to expose thin layers of
the material continuously to a vacuum (29.5" Hg) and at
the same time transfer the material from the mixing tank
to the container that will be used at the capsulation
machine.
 Suspensions or liquid mixtures containing volatile liquids
or liquid surface active agents as chief constituents of the
formula may be deaerated by subjection to temperatures
up to 60°C for the period required to achieve the results
desired.
 After deaeration, the mixture is ready to be encapsulated.
Microencapsulation
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
Air suspension
 generally ascribed to the inventions of Professor Dale E.
Wurster during his tenure at the University of Wisconsin
 consists of the dispersing of solid, particulate core materials
in a supporting air stream and the spray-coating of the air-
suspended particles.
 particles are suspended on an upward moving air stream as
indicated in the drawing
 The design of the chamber and its operating parameters
affect a recirculating flow of the particles through the coating
zone portion of the chamber, where a coating material,
usually a polymer solution, is spray-applied to the moving
particles.
 The air suspension process offers a wide variety of coating
material candidates for microencapsulation.
 The process has the capability of applying coatings in the
form of solvent solutions, aqueous solutions, emulsions,
dispersions, or hot melts in equipment ranging in capacities
from one pound to 990 pounds.
 applicable to both microencapsulation and
macroencapsulation coating process
Coacervation-Phase Separation
 the general outline of the processes consists of three
steps carried out under continuous agitation: (1) formation
of three immiscible chemical phases; (2) deposition of the
coating; and (3) rigidization of the coating
Multiorifice-centrifugal Process
 depicts a rotating cylinder. 1. a major and essential portion
of the device. Located within the cylinder are three
circumferential grooves, 2, 3, and 4
 The upper and lower grooves, also located circumter-entially
around the cylinder, carry the coating material in molten or
solution form, via tubes, 5 to the respective grooves.
 The ridges of the coating material grooves, 2 and 4, serve
as a weir over which the coating material overflows when
the volume of the upper and lower grooves is exceeded by
the volume of material dumped into the system
 The coating material, 6, under centrifugal force imparted by
the cylinder rotation, flows outward along the side of the
immediate groove into the countersunk portion and forms a
film across the orifice.
 A counter rotating disc mounted in the cylinder. atomizes or
disperses the core material fed through the centrally located
inlet, 8.
 The impact and centrifugal force, generated by the rotating
cyl-inder, hurls the core material through the enveloping
coating membrane, which is immediately regenerated by the
continually overflowing coating material.
Pan Coating
 become widespread in the pharmaceutical industry,
 with respect to microencapsulation, solid Particles
greater than 600 micrometers in size are generally
considered essential for effective coating, and the
process has been extensively employed for the
preparation of controlled-release beads.
 In practice, the coating is applied as a solution, or as an
atomized spray, to the desired solid core material in the
coating pan.
Spray Drying and Spray Congealing
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Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
 Because of certain similarities of the two processes, they
are discussed together.
 Both involve dispersing the core material in a liquefied
coating substance and spraying or introducing the core-
coating mixture into some environmental condition
 The difference between the two is the means by which
coating solidification is established
 Coating solidification in the case of spray drying is
affected by rapid evaporation of a solvent in which the
coating material is dissolved.
 Coating solidification in spray congealing methods is
accomplished by thermally congealing a molten coating
material or by solidifying a dissolved coating material by
introducing the coating-core material mixture into a
nonsolvent.
 Removal of the non solvent or solvent from the coated
product is then achieved by sorption, extraction, or
evaporation techniques.
Solvent Evaporation
 This technique has been used by companies to produce
microcapsules
 The processes are carried out in a liquid manufacturing
vehicle.
 The microcapsule coating is dissolved in a volatile
solvent.
 'The solvent evaporation technique to produce
microcapsules is applicable to a wide variety of liquid and
solid core materials.
Polymerization
 A relatively new microencapsulation method utilizes
polymerization techniques to form protective
microcapsule coatings in situ.
 The methods involve the reaction of monomeric units
located at the interface existing between a core material
substance and a continuous phase in which the core
material is dispersed.
New Designs of Capsule Formulation
PROCAPS
UniGel
 a revolutionary smart softgel from ProCaps
 allows multi-functional ingredients to exist in one dose
 softgel capsule can contain a second solid dosage form,
in softgel, tablet or granule form, enabling multi-active
formulations for unique prescription, OTC and
nutraceutical products
ChewGels
 chewable soft capsules designed to create a new
sensory experience for customers
 its shell supports solutions, suspensions, pastes and
emulsions, and the lipid coating masks unpleasant
tastes.
VersaGel
 a vegetarian softgel that is suitable for the encapsulation
of high viscous, semisolid or high pH contents
 more stable than proteins at extreme pH values and
moderate ionic strength, the ability to encapsulate high
temperature fills, and being better for the environment.
Animal Capsules
Gelatine/PEG Capsules
PH MANUF TRANSCRIBED BY: MARK HAROLD C. GONZALES
 less brittle
 good for hygroscopic and moisture-sensitive ingredients
 odorless, tasteless, three years shelf life
 PEG improves the mechanical strength of the capsule
 gelatin/PEG capsules have equivalent mechanical
strength to standard gelatin capsules
LiCaps
 two-piece gelatin as well as HPMC capsules that have
been designed to be sealed for secure containment of
liquids and semi solids.
 provides an attractive and viable dosage form,
particularly for poorly soluble compounds
POSILOK
 the registered trademark for the locking system used by
Qualicaps
 ensures that the contents reach the consumer intact, and
are protected at all times from external contamination.
Ocean Caps Fish Gelatin Capsule
 marine-based capsule, well-matched to the needs of
health conscious consumers
 ideally suited for marine supplements
 made from high quality, farmed fish gelatin
 preservative-free, starch-free, gluten-free
Non-Animal Capsules
Hydroxypropyl Methylcellulose (HPMC) Capsule
 becoming more popular in the market
 great potential alternative to gelatin-based formulations
 a safe drug for human consumption and a good
alternative for gelatin capsules because of the vegetable
source.
 widely preferred in clinical trials
 these capsules have lower moisture content
Starch Capsule
 alternative to hard gelatin capsules
 made from potato starch
 suitable for enteric coating
 consist of cap and body which are sealed together at the
time of filling to prevent separation
 sealing is achieved by applying a hydro alcoholic solution
to inner section of the cap, immediately prior to its being
placed on the body
Recent Advances in Capsule System
PORT Capsule Technology
 port stands for Programmable Oral Release
Technologies that use a unique coated in capsulated
system with opportunity to provide multiple program
release of drug
 unique and desirable release profile
 inside coated capsule is the osmotic energy source
 capsule is sealed with the water in soluble lipid
separators
Hydrophilic Sandwich Capsules
 simple and time delayed probe capsule
 capsule within a capsule
 when the outer capsule dissolved, the sandwich of
HPMC formed a gel barrier layer that provided a time
delay before fluid could enter the inner capsule and
cause drug release
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Manufacturing Dr.Kim Alexandra Pedrosa
AY 2023-2024 09/12/2203
1st Semester
Inner Cap Technology
 consists of high potency insoluble active in a lipid
emulsion, sustained-release tablet and a cocktail of two
crystalline active materials
 can deliver compatible and incompatible drugs using
different phase
 combination consists of a primary HPMC capsule
containing an emulsion, pH coated tablet etc.
Capsule Camera
 most recent innovation in GI endoscopy
 contains a video camera that captures bowel for 8 hrs
after the capsule has been digested orally and transmits
the images for interpretation to a computerized
workstation
 easy to perform and painless

REFERENCES
 Ansel ’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 9th Edition.
(2010b). The Journal of Pharmacy Technology, 26(3), 167–168.
https://doi.org/10.1177/875512251002600315
 Lachman, L., Lieberman, H. A., & Kanig, J. L. (1970). The Theory and practice of
Industrial Pharmacy. http://www.gbv.de/dms/bs/toc/016558898.pdf
 PARKE DAVIS TYPE 8 CAPSULE FILLING MACHINE, MISCELLANEOUS TOOLING -
Wohl Associates. (2021b, December 16). Wohl Associates.
http://www.wohlassociates.com/used-encapsulators-capsule-fillers/parke-davis-type-8-
capsule-filling-machine-miscellaneous-tooling.html
 Pharmapproach. (2021b). Manufacture of soft gelatin capsules. Pharmapproach.com.
https://www.pharmapproach.com/manufacture-of-soft-gelatin-capsules/
 Recent advances in capsule. (n.d.). https://www.slideshare.net/rionrasala/recent-
advances-in-capsule?
fbclid=IwAR0DcjJD9DK96HRaa8jWTsGaRLJDFxYpVo66JNsEH_s60hvqyIp81GM6LeY
 Remington: The science and practice of pharmacy. (1996). Trends in Pharmacological
Sciences, 17(4), 175. https://doi.org/10.1016/s0165-6147(96)90065-6
 Shanmugam, S. (2017). Granulation techniques and technologies: recent progresses.
Bioimpacts, 5(1), 55–63. https://doi.org/10.15171/bi.2015.04
 Recent advances in capsule. (2021). Slideshare.net.
https://www.slideshare.net/rionrasala/recent-advances-in-capsule?
fbclid=IwAR2GyKBqeCHbFdo26UVorsj1MbMul5vqtTPdjTSNTrPyyQ-8ajERXQKXIm0
 Thompson, N. (2022, August 22). Compliance to convenience: understanding the latest
innovations in capsule formulation. Pharmaceutical Technology; Pharmaceutical
Technology. https://www.pharmaceutical-technology.com/sponsored/compliance-to-
convenience-understanding-the-latest-innovations-in-capsule-formulation/

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