TABLET FORMULATION: THEORY

INTRODUCTION

Despite the advances of other pharmaceutical forms such as capsules, tablets have
gained importance in recent decades. The development of tablets must be related to the
advantage of making powdered and shaped pharmaceutical preparations available to the
patient. From an industrial point of view, they have the advantage of being produced
quickly and economically, resisting handling and storage for more or less long periods
of time due to their good stability. Until a few years ago, the preparation of tablets was
based on empirical considerations rather than scientific knowledge; In recent years this
ideology has changed since the art of making tablets has moved on to the science of
tableting.

Currently they constitute one of the most used pharmaceutical forms, since it has been
calculated that they constitute approximately 40% of all medications found in the
pharmaceutical market.

DEFINITION

They are solid pharmaceutical forms of unit dosage that contain one or more active
ingredients with or without additives, varying in shape, size and weight.

SPECIFICATIONS

 Exterior finish. - For psychological and aesthetic reasons, the tablets must have
an impeccable appearance, their surface must be smooth and intact, uniform in
color, they cannot have exfoliated layers and, when possible, a good shine.
 Dose accuracy. - The technology used in its manufacture must assume that the
active ingredients are uniformly distributed in the mass of the tablets, so they
must be exactly dosed.
 Hardness. - Standard testing in all laboratories where tablets are manufactured,
both in terminal control and in-process control; because it is a test that ensures
the availability of the medication to the patient at the time it is needed.
 Friability or mechanical resistance.- A property related to hardness is
friability, the tablets must be able to be manipulated without suffering damage in
their integrity, withstanding the mechanical stresses to which they are subjected
in the packaging, handling and transportation processes.
 Disintegration time.- This test allows us to know the capacity of a tablet, when
placed in an immersion fluid, to disintegrate into more or less fine particles, in
such a way that when the active ingredient is released, it can be dissolved to be
ready for absorption processes
CLASSIFICATION OF TABLETS

Tablets are classified under different points of view.

According to your field According to your According to its shape

of action technology

Oral use normal Round

Buccal or sublingual Effervescent Oblong

Vaginal Submitted action Triangular

Prepare solutions multilayer Square

Rectangular

hexagonal

TABLET FORMULATION

In the tablet formulation the following components can be noted:

Active principle

It is the main drug whose action defines the medication and the physical-chemical
properties determine the nature of the excipients.

Excipients or adjuvants

The excipients or adjuvants are the substances that will allow the pharmaceutical form
to be given its own characteristics.

With these adjuvants, also known as inactive ingredients, we have to be very careful
since modern Bioavailability studies prove that these substances, apparently inactive,
influence the entire formulation by modifying its biopharmaceutical characteristics,
therefore an appropriate selection must be made. of the excipients during the
preformulation processes, in order to optimize the biopharmaceutical characteristics of
the medicine. These adjuvants take different names depending on the role they play in
the formulation:

Thinners or fillers
They are the materials that allow the tablet to be given body, that is, a practical size for
the compression process and thus obtain the final weight of the tablet. Among the large
number of these materials we can mention the following:

 Lactose. - It is one of the most commonly used diluents due to its low cost and
excellent qualities: soluble in water, stable and compatible with a large number
of active ingredients.
 Starch.- It is the oldest of the materials used as diluents in tablets. For its use, it
must be taken into account that it normally has between 8 and 14% humidity, so
it must be dried to 4 to 6%. In the world market you can find certain corn
starches treated in such a way that they help excellently with direct compression.
 Sugar. - Another material used as a diluent, it is recommended to associate it
with starch and lactose, soluble in water. It has good cohesive qualities and
generates a pleasant flavor to the tablets.
 Dextrose. - It corresponds to approximately 75% of the sweetening power of
sugar and is widely used in chewable tablets.
 Mannitol and Sorbitol. - These polyalcohols are widely used as diluents in the
production of tablets by the direct compression method.
 Dicalcium phosphate. - It is the most used among inorganic diluents, due to its
good fluidity.

BINDERS

Its function in the tablet is to give cohesion and adhesiveness to the powders that make
up the granules, which ensures that the tablet remains intact after compression. There is
a wide variety of binders among which we can classify the following:

Product name % of preparation % formulation

Acacia Gum 10 - 20 p/v 2-5

Jelly 10 - 20 p/p 1-4

Sugar 64 p/p - 85 p/v 2 - 20

Starch 10 p/p 1-4

Methyl cellulose 1-5 1-4

LUBRICANTS

Its function is to ensure the fall of the granules from the hopper towards the die of the
machine, reduce the friction between the particles of the granules and prevent adhesion
to punches and dies. The different materials used as lubricants are the following:
 Product name % in the formulation

Ca,Mg stearate 1-2

talcum powder 1-5

stearic acid 1–5

Starch 5 – 10

Hydrogenated vegetable oils 3-5

liquid petroleum 1–2

Silicon dioxide 1–2

The most efficient lubricants are water-insoluble materials, since they have lipophilic
properties.

Another aspect that must be taken into account when using lubricants is the way of
incorporating it into the granules. It is recommended to use it finely divided, passing it
through an 80 or 100 mesh and incorporating it just before the final mixture, in order to
obtain greater contact surface and that the particles are present throughout the granules
and between the parts of the tabletting machine, that is, punches and matrices.

DISINTEGRATORS

It is any substance or mixture of substances that is added to a tablet to facilitate its

disintegration or disintegration after administering it. There are many materials that can
be used as disintegrators; The most used are the following:

 Starches.- They are the oldest disintegrants, which are still the most popular,
they are very dry and pulverized corn and potato starch. Starch has a great
affinity for water and swells when moistened, making it easier to break the
tablet. It is used at 5% and can be increased up to 15% if a faster disintegration
is desired.
 Cellulosic derivatives.- Such as Carboxy Methyl Cellulose (CMC), which
exists in several types from which it must be selected after the respective galenic
tests. Example: Avicel or microscribal cellulose that is used especially in direct
compression processes with excellent results.
 Clays.- Among those we have the Veegun, Bentonite (Aluminum and
magnesium silicate).
 The disintegrating agent is usually mixed with the active components and
diluents before granulation. In some cases it is advantageous to divide it into two
portions, one part is added in the granulation and the rest is mixed with the
lubricant and added before compression.
 Carbon dioxide.- The release of CO2 is also an effective way to decontaminate
tablets. Tablets containing a mixture of sodium bicarbonate with an organic acid
are effervescent when brought into contact with water. A drawback of this type
of disintegrator is that the tablets must be in a dry environment at all times
during manufacturing, packaging and storage.

Dissolvable effervescent tablets are a popular way to dispense aspirin and non-caloric
sweeteners.

Moisture maintainers

The addition of wetting agents is done to avoid complete drying of the tablets. They
improve disintegrability and can prevent exfoliation.

The different types of starches, in addition to their function as excipients and

disintegrants, also function as moisture-maintaining agents. They are capable of
absorbing moisture from the air and preventing total drying. Multiple alcohols are also
used by adding them to the granulation liquid up to 2%.

Coloring agents

In addition to improving the appearance of the pharmaceutical form, it helps the

manufacturer maintain control of the product during its preparation and also serves as
identification for the user. All colorants used in pharmaceutical products must be
approved and certified by the FDA. The most common method of adding color to a
tablet bottle is to dissolve the colorant in the binder solution before the granulation
process.

An issue that must be taken into account is the tendency of dye migration in the wet
granules during the drying process, which generates an uneven distribution of the dye,
which will produce mottled tablets. This can be avoided by drying the granules at low
temperatures and stirring them during drying.

Flavorings

In the case of flavoring agents, we can mention that some diluents such as mannitol,
lactose or sugar already generate, per se, the sweetening action; However, artificial
flavorings may be included.
MANUFACTURING METHODS

In general, it can be said that tablets can be made by 2 methods:

1. Compression
2. Molding

While the first method is the most used currently, because it is used on a large scale, the
molding method is used on a small scale and is not of major importance today.

For the preparation of tablets by the Compression method, two general routes can be
used: Dry Route and Flumeda Route.

dry route

 Direct Compression
 Dry Granulation
 Granulation by Fusion or Dispersion Exit

Direct Compression

As its name indicates, it consists of making the tablets directly without prior treatment.

Previously, direct compression was reserved for a small group of chemicals that had all
the physical characteristics necessary for the formation of a good tablet. This group
includes substances such as: potassium salts, chlorides, chlorates, bromides, iodides,
nitrates, permanganates, ammonium chloride and methenamine. These materials have
coherent and fluid properties that enable direct compression.

Currently, the pharmaceutical industry, with the desire to improve the efficiency of
operations and reduce costs, is paying a lot of attention to this method of producing
tablets. Among the approaches adopted to make this method more widely applicable is
the use of additives capable of imparting to the formulation the characteristics necessary
for compression. Commercially available direct compression vehicles contain small
amounts of other constituents such as starch to aid processing.

The excipient that has been extensively studied as a vehicle for direct compression is
Microcrystalline Cellulose (Avicel). This non-fibrous form of cellulose is obtained from
acid-treated, washed and dried cellulose that is sold in various degrees of particle size
ranging from 20 to 10011. It is insoluble in water but the material attracts liquid to the
tablet by capillarity; It swells when wet and therefore acts as a disintegrating agent.
Both pharmaceutical equipment manufacturers and the gradual improvement of
formulation additives indicate that Direct Compression will be the Preferred Method of
the Future.

Process steps

 Sieve
 Mingle
 Lubricate
 Compress

Dry granulation method

This method is used when the tablet components are sensitive to temperature and
humidity; and when the constituents possess sufficient cohesive properties. This method
is also known as Pre-compression or Double compression.

The process consists of compressing the powders into a fairly dense mass, forming the
so-called Ingots, this being the fundamental part of the process. The powdered material
contains a large amount of air and when compressed, this air is expelled and ingots are
formed in which flat-faced punches with diameters of 20 to 24 mm are used. These
ingots are crushed through a desirable mesh or with a mill appropriate for the purpose.

In recent years the ingot formation process has been replaced by the use of compactors
forming hard sheets of fine powder. The sheets thus obtained are subjected to the
granulation-sieving process to equalize the size of the granules; Then the lubricant is
added, mixed and compressed.

This method is used to tablet aspirin, vitamin C, thiamine, magnesium hydroxide and
other antacids. The tablets obtained have excellent characteristics and there is a
considerable reduction in working time.

Process steps

 Sieve
 Mingle
 Pre-compress (ingot)
 Sift granules
 Lubricate
 Compress
Granulation by fusion or solid dispersion

This is a modern method and consists of the distribution homogeneous of one or more
active ingredients in an inert carrier or matrix, which is initially a solid and which is
subsequently melted in order to carry out the process.

Process qualities due to rapid dissolution mechanism:

1. Reduce particle size

2. Solubilizing effect of the carrier
3. Absence of drug aggregates and agglomerates
4. Wetting of the tarmac() by the carrier

Advantages

1. Increases dissolution, absorption and therapeutic efficacy

2. Prevents degradation of the signature
3. Allows dosing of liquid drugs
4. Allows formulating products with sustained action
5. Fast and economical process

Limitations

1. Decomposition of drugs and/or excipients during the fusion process

2. Loss of drug and/or carrier due to evaporation
3. Generally, the carrier should be at least 50% of the mixture with the drug.

Process steps

 Sieve
 Melt the carrier
 Mix with drugs and excipients Cool
 Break up the granules
 Sieve
 Mix – lubricate
 Compress

Substances used as carriers

 Ethylene glycol condensation products: PEG 4000, PEG 6000

 Sugars: mannitol, sucrose, sorbitol
  Fatty acid esters: glyceryl monostearate Fatty acids: stearic, palmitic
 Fatty alcohols: stearylic, cetyl Waxes: bee, carnauba

Via Humeda

wet granulation

This is the most used and general method for preparing tablets. Its popularity is due to
the fact that it is safer because the granulation satisfies all the physical requirements for
the compression of good tablets. Its disadvantages are the number of individual steps
and the time required to perform the procedure.

TO. Preliminary mix

The devices required depend on the quantity or batch size. For small batches the
constituents can be mixed in stainless steel or porcelain mortars. For larger quantities,
larger capacity mixers such as the Patterson - Kelly or Planetarios are used.

The mixing time is very important to determine exactly, since an excess of this can
cause loss of homogeneity of the system due to the different densities of the powders.
The optimal mixing time can be recommended between 20 and 30 minutes, unless there
is some production need to increase or decrease this time.

b. Preparation of the binder solution

While the powder mixing process occurs, the binding agent is prepared using the
respective vehicles according to the formulation; In this phase, the dissolved dye can be
incorporated into the vehicle.

c. Granulation - Sifting

The cohesive agent solutions are added to the mixed powders under stirring until the
granules are perfectly moistened: as the granules become moistened, they acquire
greater resistance to stirring, so the stirring speed can be increased.

The wet granulation process must be conducted until the so-called "Frost Point" is
obtained, that is, the formation of small, completely coated and moistened granules.
If the granules are too moistened the granules will be hard and great pressure will be
needed to melt the tablets, if the powder mixture is not moistened enough the granules
will be too soft and will cause difficulties during compression.

Once the dry granules are ready, we proceed to the Granulation-Sifting process in order
to regulate the size of the granules; Passing the wet granules forcefully through a 6 or 8
mesh if it is small quantities, for larger quantities industrial granulators are used.

d. Drying

The material that comes out of the wet grinding is placed on shallow trays and dried in
drying cabinets with air flow and thermostatic control.

While until recently tray drying was the most widely used method, currently Fluid Bed
drying is equally popular.

In the fluid bed dryer the material is suspended and agitated in a stream of hot air while
the granulation is kept in motion. This method is 15 times faster than the conventional
tray dryer since the time required for drying is only 40 to 60 minutes, while the previous
one is 12 to 16 hours.

AND. Granulation — Retaming

Once the granules are dry, Granulation - Re-taming is carried out in order to uniform the
size of the granules; Here the residual humidity must also be determined, within the In-
Process Control, to know the optimal percentage of humidity.

F. Final mix and lubrication

The granules obtained are loaded into the powder mixer, adding the lubricant previously
sieved through 80-100 mesh to eliminate small lumps and increase the covering power.
Times of 10 to 15 minutes are recommended and the product is ready for compression.

Process steps

 Sieve
 Mingle
 Prepare the binder
 Granular to the point of frost
 Granulation — sieving
 Dry off
 Re-stamping of the granules
  Mix — lubricate
 Compress

EQUIPMENT USED

For the compression process, there are 2 types of tablet presses: Eccentric and Rotary,
each with its own characteristics.

eccentric tablet press

They are the simplest machines for obtaining tablets, they are widely used in
experimental work, to prepare test batches, but they are also used for industrial
processes although their capacity is not very high. The characteristic of this equipment
is that the die remains stationary while the feeding hopper moves.

Rotary tablet press

These machines are very advantageous for large-scale production. The characteristic of
this equipment is that the hopper remains stationary while dies and punches rotate. The
technological advance achieved in the production of rotary tableting machines currently
allows machines with 1, 2 and 3 feeding hoppers, the sets of punches and dies can vary
between 3 and 55 and their production can be between 20,000 and 120,000 tablets per
hour. .

Fundamental parts of a Tablet Press

Every Tablet Press has its fundamental parts that do not change no matter how old or
modern they are:

 Plate where the matrix goes

 Feeding hopper where the granules are deposited Matrix where the tablet is
formed
 Lower punch regulates the size and weight of the tablet
 Upper punch exerts pressure on the granules to form the tablet
 Gear system with mechanical devices that allow synchronized movements to
the whole.

Compression stages:
  Loading: The lower punch descends as much as possible, the upper punch rises,
the hopper advances until it is positioned above the matrix and fills it with the
granules.
 Compression: The lower punch retains its position, the hopper is removed and
the upper punch penetrates strongly into the matrix and forms the tablet.
 Unloading: The upper punch rises, the lower punch rises to the edge of the
platen and the hopper advances so that its free edge collides with the tablet and
removes it from the machine.

TECHNOLOGY

The technology to make tablets is carried out according to the nature of its components,
which implies applying the correct method. Naturally, each tablet requires certain
particularities in its production, even more so at an industrial level, which is made
possible by using the appropriate equipment and instruments.

PACKAGING AND CLOSING SYSTEM

The tablets are generally packaged in a blister system, aluminum strips and in a plastic
or glass bottle. In addition to the packaging, it must be verified that the closure system
protects the product from the environment. Subsequently, stability tests will be carried
out on the final container to determine if there are no interactions with it.

LABELED

As it is a product in the development phase, the labeling must contain data relating to
the product such as: Pharmaceutical form, trial #, active ingredient(s), concentration,
date of manufacture, time, name of person responsible, signature, group/day and
subgroup. These data are contained in the Drug Formulation label.

STORAGE

The tablets should be stored in cool places and protected from light, which are measures
to maintain the stability of the product.

QUALITY CONTROLS

The tablets must be controlled to demonstrate their quality through tests that verify that
the product meets the specifications. These are the following:
TO. - In the granules

Humidity:

It is important to perform this test before the compression process, in order to ensure
compliance with the specifications. Any equipment can be used for this purpose. The
limit values, depending on the type of granules, can vary between 0 - 4%.

Uniformity of content:

This test can be carried out on the granules as a validation method of the mixing
process. A sample must be taken from the lower, upper and middle parts of the mixing
tank and in these samples the active ingredient content must be assessed, which must be
within the product specifications.

b. - On the finished tablet

Organoleptic Characteristics

 Appearance: The presentation of the tablet must be described. Specification:

Impeccable, without peelings
 Color: At the same time as observing the appearance, the color is appreciated.
Specification: It must be the one that has been determined for the tablet
 Shape: Round, oblong. Triangular, square, rectangular, hexagonal, etc.
Specification: The one that has been determined for the tablet.

physical characters

Diameter, thickness, grooves and/or logo

 Ditimeter: It is the width of the tablet if it is round . The test is carried out using
a vernier caliper that allows us to have an exact value.
 Specification : The one that has been determined for the tablet

Procedure

 Place the tablet diametrically in the widest part of the vernier and secure it by
tightening the screw at the top of the vernier.
 Note that the zero at the bottom determines the whole millimeters
 Then, using the magnifying glass, observe which of the lines on the lower scale
coincide exactly with the upper scale and thus determine the decimals.
  Use a sample of 5 tablets and calculate average

Thickness:

 It is the height of the tablet

 The test is carried out using a vernier caliper that allows us to have an exact
value. Specification: The one determined for the tablet

Procedure

 Place the tablet on the vernier so that its height is determined and secure it
 tightening the screw on the top of it
 Note that the zero at the bottom determines the whole millimeters
 Then, using the magnifying glass, observe which of the lines on the lower scale
coincide.
 exactly with the upper scale and thus determine the decimals. Use a sample of 5
tablets and calculate average

They have grooves and/or logo:

They are the grooves and/or logo of the brand

Specification: According to the slots and the logo of the specific brand for the tablet

Determination of average weight:

While the compression process lasts, weight variation control should be carried out
every 30 minutes. For this purpose, the specifications set forth in the United States
Pharmacopeia are taken as the standard, whose tolerances are the following:

Average tablet weight % variation

Up to 130 mg 10%

From 131 to 324 mg 7.5 %

From 325 mg onwards 5%

Procedure

A sample of 20 tablets is taken and weighed individually, the weights are noted, and the
average weight is calculated; The individual weights of 18 tablets must be within the
average weight ± the percentage of variation and the weight of 2 tablets can be outside
this percentage but within twice the percentage of variation.

Hardness:

The resistance of the tablet to chipping, abrasion or breaking under conditions of

storage, transportation and handling before use depends on its hardness. For this test,
samples must be taken every 30 minutes during the compression process. Hardness is
measured in Kilograms - force (kiloponds), Strong - Cobb Units or Newtons. To carry
out the test there are some pieces of equipment:

 Monsanto meter.- Which measures the force required to break a tablet when the
force generated by a coil spring is applied diametrically to the tablet.
 Strong-Cobb meter.- It also measures the force applied diametrically on the
tablet; This force is operated manually by an air pump; The end point is
expressed on a dial calibrated generally with 30 USC (Strong - Cobb Units).
 Heberlein meter.- It is the equipment that is most used in the pharmaceutical
industries; It has a pair of jaws that move horizontally and when they come into
contact with the tablet, they activate a pressure distributor and the needle, which
marks the pressure value, which is read on a dial calibrated in Newtons or Kg -
force.

Friability

A property related to hardness is the friability of the tablet, which is measured with a
Roche apparatus. This instrument is designed to evaluate the ability of the tablet to
withstand abrasion during packaging, handling and transportation. 20 tablets are
weighed and placed in the apparatus, where they are exposed to repeated rolls and
impacts due to free falls within the apparatus. After a given number of rotations, the
tablets are weighed and the weight loss indicates their ability to withstand this type of
wear.

Procedure

 Sample: 20 tablets, weigh exactly: Initial weighing

 Place in a 100 mL container and cover with aluminum foil.
  Shake gently for 3 minutes.
 Carefully remove the dust and weigh again: Final weighing.
 Calculate friability % = Initial weight - Final weight x 100
Maximum limit 1%

Physical - chemical characteristics

Disintegration:

This test allows us to know the capacity of a tablet, when placed in an immersion fluid,
to disintegrate into more or less fine particles in such a way that when the active
ingredient is released, it can dissolve to be ready for the processes. of absorption.

Each type of tablet according to its formulation has established its disintegration time
and its Tangos; For example, aspirin tablets should disintegrate in 2 to 5 minutes. The
USP describes a technique that is mandatory for all tablets, except for those to be used
as troches or to be chewed and those for sustained action.

The disintegration time depends on the active ingredients, adjuvants and the pressure
applied during compression. To carry out the test, a device is used that consists of:

A 1 liter capacity glass in which the immersion fluid is placed, this glass must be
connected to a bar of water with a thermostat in which the temperature of the immersion
fluid can be controlled at 37 °C ± 2 °C . A basket containing 6 test tubes, made of
transparent material, with an approximate length of 7.75 cm and an inner diameter of
2.5 cm, the inner hole is closed by a metal mesh and the upper one is completely open;
The opening holes of the meshes are approximately 2 mm. This basket is connected to
an ascent and descent mechanism that allows 30 ± 2 ascensions per minute. In each of
the test tubes there is a plastic disc, which serves to prevent the samples from floating
during the process.

Procedure

Place one tablet in each of the 6 tubes and add the disk. Fill the container with the
immersion fluid and adjust the temperature to 37 °C ± 2 °C, introduce the samples
and activate the device and start the stopwatch.

Observe the tablets carefully and note the exact time each one takes to disintegrate. The
test is satisfactory when at the end of the specified time all the tablets have
disintegrated.

Dissolution:
For certain tablets, the monographs provide for compliance with dissolution limits,
meaning that this test tells us the time it takes for the drug to enter solution, it is an in
vitro test. It is done with a view to evaluating the physiological availability of the
substance. There are 2 methods for dissolution rate testing:

Basket method and paddle method

Various immersion fluids can be used to carry out the tests.

Procedure

The dissolving liquid is placed in the glass, brought to temperature at 37°C, the
pharmaceutical form is placed in the apparatus and the operation begins at the
established speed.

Samples are extracted at the established times, introducing a pipette in the middle area
between the basket or paddle and the surface of the liquid and at a distance of no less
than 1 cm. from the wall of the glass, dissolving medium is added to replenish the
volume of the liquid removed. Filter the samples and evaluate, the test is repeated as
many times as necessary.

chemical characters

Identification of active ingredient:

1. This test must be carried out according to the specifications set out in the
Monograph.
2. Product description.

Assessment of the active ingredient:

Likewise, it must be carried out using methods indicated in the Descriptive Monograph
of the product; In general terms, the most used methods are: Thin layer
chromatography, Spectrophotometry, Liquid chromatography (HPLC).

VALIDITY OF FORM U LATION V STABILITY SHEET

The results obtained from the controls carried out serve for the design of the product
stability study. Here the variables to be considered are established: Temperature, light,
type of container, closure system and the duration of the test, which for us is 4 weeks,
for reasons of time, but these results do not reflect the real useful life of the product.
product but an attempt.
The study is carried out on the packaging and final closure system of the product to
determine the expiration date. simultaneously carrying out natural stability tests.

CONCLUSION

Analyzing the results obtained, we can conclude that if the product maintains its
characteristics during the 4 weeks, it provides us with an attempt at the useful life of the
medication; In this way, it is established, in a simulated way, that the product meets the
characteristics of the Prototype.

RESPONSIBILITY

The names and signatures of the people involved in the Development and Formulation
of the Medication must be recorded.
TABLET FORMULATION: PRACTICE GUIDE

Formulate the pharmaceutical formula: Tablet

Pharmaceutical formula:

Calic carbonate…………………..315 mg

Excipients csp………………………1 tablet

GOALS

 Carry out the physical-chemical study of the active ingredient to determine the
most appropriate excipients in the recommended quantities.
 Select equipment and materials, container system and closure.
 Establish basic production procedure and quality controls.
 Determine validity of the formulation through the stability study.

Methodology:

Wet compression

Phase A. Verify physical-chemical aspects of the Active Ingredient

 Name: Calcium Carbonate

 Synonymy: Calcium salt of carbonic acid, Precipitated chalk, Precipitated
calcium carbonate
 Description: It appears as a fine, white, microcrystalline powder with no odor or
flavor and is stable in air. The aqueous solution is practically neutral against
sunflower seeds.
 Solubility: Practically insoluble in water, insoluble in alcohol, it dissolves with
effervescence in dilute acetic acid, hydrochloric acid and nitric acid.
 Uses: Fast-acting antacid, used as a toothpaste and to make antacid suspensions.

Phase B. Study of excipients and recommended quantities

- Active ingredient: Calic carbonate…………………………….315.00 mg

- Excipients: Diluent or filler: Lactose…………………………..104.35 mg
- Disintegrant: Starch……………………………………………...41.35 mg
 - Lubricant 1: Talc……………………………………………….17.65 mg
- Lubricant 2: Stearic Acid powder………………………………7.30 mg
- Colorant: 10%
solution................................................ ...............................Calculate
- Binder: Starch paste 10% ………………………………Calculate

To calculate the theoretical weight of the tablet, it is based on the amount of binder and
colorant used compared to the number of tablets to be obtained.

Example of calculating the theoretical weight of the tablet:

Split granule quantity__________________ amount of binder: 21.11

Remaining ___________# tablets obtained: 150 # of tablets obtained_____

Calculations:

10 g . almidon 21.11g .aglutinante

100 g . aglutinante
x x g , almidon
= 2. 111 g starch

2 ,111 g de almidon 1 Tb
150Tb
x x g de almidon
= 0.01407 = 14.07 g of starch used

Amount of dye used: 2 mL

10 g colorante 2ml solucion

x
100 ml solucion x g de colorante
= 0.2g = 200mg

200 mg . colorante 21.11g .aglutinante

x
100 g . aglutinante x mg de colorante
= 42.22 mg
42.22 mg .colorante 1 Tb
150 Tb
x x mg de colorante
= 0.28 mg of dye

Theoretical weight of the tablet and percentage of ingredients in the formulation:

- Calcium Carbonate ……………………315.00 mg 63.00 %

- Lactose …………………………………104.35 mg 20.87 %
- Starch ………………………………… 41.35 mg 8.27 %
- Talcum powder……………………………………. .17.65mg 3.53 %
- Stearic Acid Powder……………………. 7.30 mg 1.46 %
- Colorant: 10% solution …………………. 0.28mg 0.06 %
- Binder: Starch paste 10% ………...14.07 mg 2.81 %

500.00 mg

Phase C. Establish Unitary Formula pre - prototype

code Raw material Unitary Unit C/ industrial Unit

Street

SC33 Calcium carbonate 315.00 mg 47.25 g

SL1 Lactose 104.35 mg 15.65 g

SA13 Starch 41.35 mg 6.20 g

ST1 talcum powder 17.65 mg 2.64 g

SA5 Stearic Acid Powder 7.30 mg 1.10 g

SC17 10% yellow dye 0.28 mg 0.042 g

SPA 10% starch paste 14.07 mg 2.11 g

Total granules 500.00 mg 75.00 g

ELABORATION PROCESS

Select equipment and materials to use

Equipment Glass material Additional material

Single plate electric scale 250 mL Beaker (1) steel spatulas

Precision balance 100 mL test tube (1) porcelain mortar

Sieves #6 - 10 60-80 Test tube 50mL (1) Kraf Paper

electric reverberatory pipettes 5mL (1) grease paper

Drying stove stirring rod (1) News paper

manual tablet press Formulation label

Disintegrator plastic case

Vernier caliper Fine brush or brush

Time clock or stopwatch Magnifying glass

Weighing of raw materials

code Raw material Quantity Tare Gross Net signature

to weigh weigh weigh weight
t t

SC33 Calcium carbonate 47.25

SL1 Lactose 15.65

SA13 Starch 6.20

ST1 talcum powder 2.64

SA5 Stearic acid powder 1.10

SC17 10% yellow dye 0.042

SPA 10% starch paste 2.11

 Flowchart

Sieve

Mingle Moisten

Granular Dry off

Re-sieve Lubricate

Compress Mingle

Package

Label

Preparation of the Binder Solution

 10% starch paste

- Weigh 10 g of starch
- Mix with 28 mL of cold water
- Add 2 mL of the 10% dye solution.
- Add 60 mL of boiling water while stirring.
- Stir on the heat source until a solid paste is formed.
- Cool slightly and weigh with the rod and record weight

13ASIC PREPARATION PROCEDURE

Instructions/Operations Signature

1. Sieve the Calcium Carbonate, lactose and half of the starch through 60 mesh.
2. Mix in a plastic bag for 2 minutes.
 3. Transfer the mixture to a mortar
4. Moisten little by little with the hot binder until frost point.
5. Weigh and record amount of binder
6. Granulate by forcing the dough through a #6 sieve onto a Kraf paper tray. Drop
the granules with a steel spatula
7. Dry the granules in an oven between 55 - 60 °C for 12 hours.
8. Label Product in the Drying Process
9. Determine % Humidity
10. Re-sieve the granules through a #10 sieve without making powder.
11. Sieve the lubricants with the other half of the starch by 80 mesh
12. Mix in the plastic bag (previously weighed) with the previous granules for 2
minutes.
13. Weigh and record amount of granules
14. On the tablet press, verify that the lower punch is facing up at the level of the
platen; and that the hopper hangs over the matrix
15. Place the granules in the feeding hopper.
16. Compress trying to maintain the same speed until the granules are exhausted.
17. Receive the tablets in a suitable container
18. Clean excess residual dust on the tablets with a brush
19. Collect all the remainder, weigh and record.

Performance

Theoretical Quantity___________________ actual number of tablets obtained

real
% performance
teorico
x 100 = _________________

Sample collection for controls

Amount of sample taken_______________________________________________

Packaging and closure system

Type of
packaging__________________________________________________________
Closing
system_________________________________________________________________
___

Labeled

Label_______________________________________________________________

Storage

Temperature_______________________________
Light____________________________

QUALITY CONTROLS

Quality characteristics Specifications

A.- In the granules

Humidity 1—4%

Uniformity of content ± 5%

B.- On the tablet

Organoleptic characteristics:

Product appearance Flawless

Color Mellow Yellow

Shape Round

Physical characteristics:

Diameter 9— 10mm

Thickness 4 — 5mm

Has grooves or logo Does not carry

Detellnination of the average weight ± 5%

Friability Up to 1%

Hardness 4 Kg — force

Physical-chemical characteristics:
Disintegration Up to 30 minutes

Dissolution 90 – 110%

Chemical characters:

Identification of Active Ingredient Calcium carbonate: +

Active Ingredient Assessment 315 mg ± 5%

TESTS TO BE CARRIED OUT

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