Khan Ramiz V

M. Pharm
Ali Allana Colg of Pharmacy Akkalkuwa
 What is Industrial Pharmacy
 Industrial pharmacy is a discipline which includes
manufacturing, development, marketing and
distribution of drug products including quality
assurance of these activities.
Preformulation :
 Preformulation may be defined as a stage of the
research and development process where the
preformulation characterizes the physical, chemical,
biopharmaceutical properties of a new drug
substance, in order to develop stable, safe and
effective dosage form.
Objectives (Why its important)
 Investigation of physicochemical properties of the new
drug compound is essential because that could affect drug
performance and development of an effective dosage form.
 To generate useful information to the formulator to design
an optimum drug delivery system.
 The preformulation investigations confirm that there are
no significant barriers to the compound’s development as a
marketed drug.
 The formulation scientist uses this information to develop
dosage forms.
 Preformulation starts when a newly synthesized drug
shows a sufficient pharmacologic promise in animal model
to warrant evaluation in man.
Goals of Preformulation
• To find the necessary physicochemical properties like
solubility, crystal form of new drug substances.
• To determine kinetic release of drug from dosage
form.
• To establish physical characteristics.
• To establish compatibility (no interaction) with
common excipients.
PHYSICAL PROPERTIES
 It is vital to understand the physical description of a
drug substance (whether it is solid, semisolid or
liquid) prior to dosage form development.
 Most drugs in use now a days are solid materials and
less number are liquid in nature. Flow ability of
powder and chemical stability depends on the habit
and internal structure of a drug.
 The physical properties include Organoleptic
properties of the candidate drug molecule and the
excipients such as color, odor and taste.
 Colour : It should be unappealing to the eye and should
determined by either instrumental methods or visible
method that varies from batch to batch.
 A record of early batches and establishing “specs” is very
useful for later production. Coating of body in variable
colors can be done if found undesirable.
 Odour & Taste : odour greatly affects the flavor of a
preparation. If taste is unpalatable, consideration is given
to the use of a less soluble chemical form of the drug.
 The odour & taste may be suppressed by using appropriate
flavors and excipients or by coating the final products.
Drugs irritating to skin should be handled with
precautions.
 The flavors, dyes and excipients used affects stability and
bioavailability of drug.
(I) Nature of Solid Drug:
Organoleptic Properties

Colour Odour Taste

Off-white Pungent Acidic
Cream yellow Sulphour Bitter
Tan Fruity Bland
Shiny Aromatic Intense
Odourless Sweet
Tasteless
 Physical form
 Drugs can be used therapeutically as solids, liquid and
gases.
 Liquid drugs are used to a much lesser extent than solid
drugs and even less frequently than gases.
 Solid materials are preferred in formulation work because
of their ease of preparation into tablets and capsules.
 The majority of drug substances in use occur as solid
material. Most of them are pure chemical compounds of
either amorphous or crystalline in nature.
 Crystal Habit and Internal structure of drug can affect
physicochemical properties which range from flow ability
to chemical stability.
 Habit means outer appearance of crystals.
 While internal structure describes the molecular
arrangement withing the solids, whereas changes in
internal structure usually alter crystal habit.
 For Example :
 Conversion of sodium salt to its free acid form
produces both a change in internal structure and
crystal habit and conversion of sodium benzoate
to benzoic acid.
 Solids compounds can also be classified based
upon their internal structure as crystalline and
amorphous.
1) Crystalline :
 Crystals are characterized by repetitious spacing of
constituent atoms or molecule in a dimensional array.
 In this state of matter atoms or molecules are arranged in
highly ordered form and is associated with three-
dimensional periodicity.
 Evaluation of crystal structure, polymorphism and
solvate form is an important preformulation activity.
 Changes in crystal characteristics can influence
bioavailability, chemical & physical stability as well as
dosage form process.
 Crystalline forms of drugs may be used because of greater
stability than the corresponding amorphous form.
 Ex : Penicillin G crystalline form as potassium or sodium
salt is considerably more stable and showing excellent
therapeutic response than amorphous form
Fig : SEM Micrographs of Some Crystal Morphologies
2) Amorphous :
 Amorphous form of the solids does not have any fixed
internal structure. They have atoms or molecules
randomly placed as in a liquid.
 Ex : Amorphous Novobiocin (Antibiotics)
 Amorphous forms are typically prepared by precipitation,
lyophilization, or rapid cooling of molten liquid (glass).
 Amorphous forms have higher solubility as well as
dissolution rates as compared to crystalline forms.
 Ex : Novobiocin is inactive when administered in
crystalline form, but when they are administered in the
amorphous form, absorption from the gastrointestinal
tract proceeds rapidly with good therapeutic response.
 Particle Size
 The particle size & size distribution of active ingredients &
excipients is an important physical characteristic of the
materials used to formulate pharmaceutical products.
 The size and particle distribution can affect bulk properties
of substance such as taste and color its performance in
terms of its suspendability, absorption rate, bioavailability,
therapeutic efficacy, processability, stability, content
uniformity and appearance of the products.
 Fine materials tend to require more amount of granulating
liquid as compared to those with large particle size when
they are processed for tablet formulation.
 Particle size significantly influences the oral absorption
profile of certain drugs such as griseofulvin, nitrofurantoin,
spironolactone etc.
 Particle size is characterized using the terms very coarse
(#8), coarse (#20), moderately coarse (#40), fine (#60) &
very fine (#80).
 Various techniques such as optical microscopy, sieving,
sedimentation (Andresen pipette), blockage of electrical
conductivity path (Coulter counter), Light blockage and
light diffraction or scattering techniques are used for
particle size estimation.
 Modification of particle size and morphology could
overcome the formulation problems such as improved drug
release.
 Surface Area :
 The surface area of powders is also an important feature of
solids in development of dosage forms.
 Surface area reflects the particle size; the lower the particle
size, the higher the total surface area of powder sample.
 According to this method the powdered particle would
absorb nitrogen gas in combination with inert gas (helium)
and form a monolayer at a specific temp and press.
 Particle Shape
 Its not only the particle size, but the particle shape and its surface
morphology also affects their surface area, flow properties, packaging
and compaction, dissolution behavior.
 Knowledge of the particle shape is essential for the understanding of
the behavior of the powder.
 It help to know the properties such as flow and deformation that
influences the processability.
 The regular and nearly spherical granules, irregular shape primary
particle or granules do not flow properly and may lead to weight
variation during capsule filling and tablet compression operation.
 When a powder is poured into a container, the volume that it
occupies depends on shape or particles.
 Irregular shape powder or granules enhance particle to particle
contact and lead strong bond formation during tablet compression
Fig : Particle shape
 Flow properties
 The flow properties of powders are critical for an efficient
tablet operation.
 During the preformulation evaluation of the drug
substance and therefore, its flow ability characteristics
should be studied, especially when the anticipated dose of
the drug is large.
 Powders may be free flowing or cohesive (non-free
flowing).
 Flow properties of powders are affected by changes in
particle size, density, shape and adsorbed moisture.
 It is characterized by Carr’s index and Hausner ratio, angle
of repose, rheology.
 The flow properties of powders are also depend upon force
of friction and cohesion between particles.
Solubility Profile (pKa, pH, Partition Coefficient)

 The majority of existing drugs and new chemical entities are

lipophilic (poor water solubility).
 The low solubility is due to high Crystallinity, high melting
point and high molecular weight of the drug or may be due to
lack of ionizable groups present in the molecules.
 However, in order to get absorbed through biological
membrane, especially at the gastro-intestinal tract, the drug
has to be in solution.
 Drug with low solubility profile are very difficult to design into
solid oral dosage form due to their poor dissolution rate.
 Even as parental preparation, to deliver in high doses.
 Most of the drugs available today are either weakly acidic or
weekly basic, their solubility increases in basic and acidic
pH, respectively, depending on their ionization state.
 Depending upon kind of dosage form to be developed
solubility studies in solvent such as propylene glycol,
glycerin, ethyl alcohol, sorbitol, methanol, isopropyl
alcohol etc at various pH are required to be performed.
 If intrinsic solubility and pKa of any drug is known its
solubility at any pH can be predicted.
 Dissociation Constant

 pKa allow us to estimate the effective charge present on a

molecule at by particular pH.
 The interrelationship between dissociation constant, lipid
solubility and pH at the absorption site and absorption
characteristics of various drugs is described in pH-partition
theory.
 The degree of drug ionization depends on pH of the
solution in which it is presented to the biological
membrane and on the dissociation constant.
 The concept of pKa is derived from the Henderson-
Hesselbalch equation...
 Determination of ionized to the unionized form,
ratio of a drug is useful to predict which form will
predominate at different physiological pH.
 Mostly, unionized form of the drug is rapidly
absorbed and consequently, acidic drugs will be
absorbed in the acidic media of the stomach and
vice versa.
 pH :
 In the development of poorly soluble drug as liquid
product solubility can be enhanced through adjusting the
pH of the solvent in which the drug is to be dissolved.
 However, there are many drugs substances for which pH
adjustment Is not an effective means of improving
solubility.
 Adjustment of pH may have little effect on the solubility of
non electrolytes, such as dextrose and prednisone.
 Partition coefficients :
 Partition coefficient is defined as the ratio of unionized
drug distributed between the organic and Aq. Phase at
equilibrium.
 PC can provide an indication of the drugs absorption
potential.
 If a solute is added to a mixture of two immiscible liquids,
it will distribute between the two phases and reach
equilibrium at a constant temp.
 The distribution of the intact solute between two
immiscible liquids can be described as ratio of the
unionized drug in organic phase (upper) & Aq phase
(lower) at equilibrium at constant temp.
 Dissolution :

 The amount of the drug substance that goes into the

solvent at particular temp that is called as dissolution
 The speed or rate at which drug substance dissolves in a
medium is called dissolution rate.
 The dissolution rate of the drug in which the surface area is
constant during dissolution is described by Noyes Whitney
equation.
 This equation reveals that dissolution rate of a drug may be
increased by increasing the surface area ( by reducing the
particle size) of the drug and by increasing the solubility of
the drug in the diffusion layer.
 Common ion effects :
 CIE refers to the decrease in solubility of an ionic
precipitate by the addition to the solution of a
soluble compound with an ion in common with
the precipitate that is called as common ion
effects.
OR
 An effects that suppress the ionization of an
electrolyte when another electrolyte (which
contains an ion which is also present in the first
electrolyte i.e common ion effects)
 (Le Chatlier’s principle)
 Nature of Solid Drug
 When a drug molecule is invented, all the solid-forms are
hardly identified. So, during bulk characterization the
following characteristics are studied.
1. Crystallinity and Polymorphism:
 Crystal habit (external shape of crystal) is the outer
appearance of a crystal. A single internal-structure for a
compound can have many different habits, depending on
the environment for growing crystals. Internal Structure of
drug may be crystalline and amorphous forms.
(i) Crystalline state:
 In this state of matter atoms or molecules are arranged in
highly well-ordered form and is associated with three-
dimensional to organize themselves into their most
favourable thermodynamic state, which under certain
conditions results in their appearance as crystals.
 The repeating three-dimensional patterns are called crystal
lattices. The crystal lattice can be analyzed from its X-ray
diffraction pattern.
 Crystal Habit: Platy, Needle, or Acicular, Tabular, Equant or
Massive, Bladed etc
 Amorphous forms:
 In this form the solids do not have any definite internal
structure.
 They have atoms or molecules disorderly placed as in a
liquid.
 e.g. Amorphous Itraconazole, Amorphous Novobiocin
 Difference between Crystalline and Amorphous Form

Crystalline form Amorphous forms

(i) Structure: Amorphous forms do not

(i) Structure: Crystalline forms have
have any fixed or no shape internal
definite ordered internal structure.
(crystal) structure.

(ii) Stability: Amorphous form has higher

(ii) Stability: Stability of crystalline forms
thermodynamic energy than its crystalline
is more stable than its amorphous forms as
form hence lesser stable than crystalline
it is having less internal energy.
forms.

(iii) Solubility: Crystalline form has lesser iii) Solubility: Amorphous forms have
solubility than its amorphous form. greater solubility than its crystalline forms.

(iv) Change to other form: Crystalline (iv) Change to other form: Amorphous
form has lesser inclination to change its be likely to revert to more stable forms
form during storage. during storage.
 (ii) Polymorphs: When a substance is in more than one
crystalline form, the various forms are called polymorphs
and the phenomenon as polymorphism.
 e.g. Chloramphenicol palmitate has three polymorphs: A, B
and C. Spironolactone exhibits 6 polymorphs.
 Polymorphs are of 2 types

Enantiotropic polymorph Monotropic polymorph

The polymorph which can be changed
from one form into another by varying
temp or press is called as
Enantiotropic polymorph.
Ex : Sulphur
One polymorphs which is unstable at
all temp & press is called as
Monotropic polymorph.
Ex : Glyceryl stearate
 Analytical Methods for Characterization of Solid
Forms:
 Methods of studying solid forms are listed as below
(amount of drug required for study):
(a) Microscopy (1 mg)
(b) Hot stage microscopy (1 mg)
(c) Differential Scanning Calorimetry (DSC) (2 - 5 mg)
(d) Differential Thermal Analysis (DTA) (2 - 5 mg)
(e) Thermo gravimetric Analysis (10 mg)
(f) Infrared Spectroscopy (2 - 20 mg)
(g) X-ray Powder Diffraction (500 mg)
(h) Scanning Electron Microscopy (2 mg)
(i) Dissolution / Solubility Analysis (mg - g)
 Liquids:
 Liquid drugs have two problems in the design of a
dosage form which are:
(i) The volatility: They must be physically sealed from the
atmosphere to avoid evaporation.
(ii) They cannot generally be formulated into tablet (the
most popular form of oral medication).
To solve these problems, two easy methods are used to
formulate liquid drugs into solid dosage forms.
(i) By soft gelatin capsule, e.g. Vitamin A.
(ii) By converting of the liquid drug into solid derivatives
such as salt or ester. For instance, scopolamine is liquid but
its hydrobromide salt is solid.
 Hygroscopicity:
 Many pharmaceutical materials have a tendency to adsorb
atmospheric moisture (especially water-soluble salt forms). They
are called hygroscopic materials and this phenomenon is known
as Hygroscopicity.
Equilibrium moisture content depends upon:
(i) The atmospheric humidity
(ii) Temperature
 Procedure: Bulk drug samples are placed in open containers
with thin powder bed to assure maximum atmospheric exposure.
 These samples are then exposed to a range of controlled relative
humidity (Relative Humidity) environments.
 The amount of moisture adsorbed can be determined by the
following methods:
(i) Gravimetry
(ii) Thermo gravimetric analysis (TGA)
 Chemical properties
 Pharmaceutical excipients may be used to achieve the
desired dosage form of a drug substance.
 Other substances, such as buffers and antioxidants, may be
used to increase the stability of the drug substance,
particularly against the hydrolytic and oxidative processes.
 In all cases, the added pharmaceutical ingredients must be
compatible with and must not detract from the stability of
the drug substance in the particular dosage form prepared.
 Drug degradation occurs by four main processes namely
hydrolysis, oxidation, and photolysis and trace metal
catalysis.
 Hydrolysis and oxidation are the most common pathways,
and in general light and metal ions catalyze a subsequent
oxidative process.
 1. Hydrolysis
 Drug molecules interact with water (drug) molecules to
yield breakdown product.
 The most likely cause of drug instability is hydrolysis.
 Water plays a dominant role and in many cases it is a
solvent vector between two reacting species in solution.
 Hydrolytic reactions involve nucleophilic attack of labile
bonds ( lactam > ester > amide > imide) by water on the
drug in solution,
 Heat, light, solution polarity, high drug concentration are
some of the conditions that catalyze the hydrolytic
breakdown.
 The simplest is the reduction, or the elimination of water
from the pharmaceutical system.
 In liquid reparations, water can frequently be replaced or
reduced in the formulation through the use of substitute
liquids such as glycerin, propylene glycol and alcohol.
 In certain parental products, anhydrous vegetable oils may
be used as solvent to reduce the possible hydrolytic
decomposition.
 In case of certain unstable antibiotic drugs, when an
aqueous preparation is desired, the drug may be
commercially supplied in a dry form for reconstitution at
the time of administration by adding a specified volume of
purified water just before dispensing.
 Along with temp, pH is a major determinant in the stability
of a drug prone to hydrolytic decomposition.
2. Oxidation

 Oxidation is a loss of electrons and oxidizing agent must be

able to take electrons.
 Oxidation is controlled by the environmental conditions
such as light, trace metals, oxygen and oxidizing agents.
 Most antioxidants function by providing electrons or labile
H+, which will be accepted by any free radical to terminate
the chain reaction of oxidation.
 The reaction between compound and molecular oxygen is
called autoxidation.
 The oxidation may result in precipitation or alter the color
or usual odor of the products.
 The oxidative degradation can be prevented by use of
antioxidants, which reacts with more than one compound
in the drug product to prevent progression of the oxidative
chain reaction. The antioxidants used in aqueous
preparations include sodium sulfite (at high pH), sodium
bisulfate (at intermediate pH), sodium metabisulfite (at
low pH).
 Light act as a catalyst by transferring their energy
(Photons) to drug molecules.
 Thus light sensitive preparations are packaged in light
resistant or opaque containers. (umber color bottle)
 3. Reduction
 Reduction is chemical reaction that involves the gaining of
electrons by one of the atoms involved in the reaction.
 Water catalyzes the chemical reduction reaction.
 Chemical reduction plays vital role in stability of a
pharmaceutical product.
 The chemical reduction in the pharmaceutical products
may lead to the formation of degradation product, loss of
potency of API, loss of excipients activity like antimicrobial
preservative action and antioxidants etc.
 Ex is ethanal reduced to ethanol by adding hydrogen.
 A reducing agent used is sodium tetrahydridoborate
(NaBH4)
 4. Recemization
 Although hydrolysis and oxidation constitute the main
mechanisms by which drugs can decompose; Recemization is
another way by which the drug can change in solution.
 In this optically active compound loses its optical activity
without change in its chemical composition.
 When the drug is converted into its inactive form due to loss of
optical activity it is called as recemic mixture.
 The interconversion from one isomer to another can lead to
different pharmacokinetic properties as well as different
pharmacological and toxicological effect.
 Levo-adrenalin is 15-20 times more active than dextro-
adrenaline.
 Recemization depends on temp, solvent, catalyst and presence or
absence of light.
 5. Polymerization
 Polymerization is a continuous reaction between
molecules. More than one monomer reacts to form a
polymer.
 For ex, Darkening of glucose solution is attributed to
polymerization of breakdown product [5-(hydroxy methyl)
furfural].
 It can also be defined as a process involved in the
combination of simple monomer molecules in order to
form large complex polymer or simply as the process of
monomer bonding that is called as polymerization.
 BCS CLASSIFICATION
 Bioavailability has an important role in new drug discovery
and product development in pharmaceutical field.
 The solubility and permeability are important parameters
of biopharmaceutics and have central role in lead
optimization by controlling the pharmacokinetic
parameters to give better therapeutic activity.
 Biopharmaceutics Classification system (BCS) is a scientific
framework for classifying drug substances based on their
aqueous solubility and intestinal permeability.
 This classification system was devised by Amidon and
coworkers in 1995.
 The BCS has found international recognition in industry,
academic institutional and research organizations.
 The objective of the BCS is to predict in vivo performance
of drug products from in vitro measurements of
permeability and solubility.
 The drugs are divided into high/low-solubility and
permeability classes.

The principle of the BCS is that if two drug

products yield the same concentration profile
along the gastrointestinal (GI) tract, they will
result in the same plasma profile after oral
administration.
 This concept can be summerized by the following equation.
J = Pw Cw
 Where, J is the flux across the gut wall
 Pw is the permeability of the gut wall to the drug
 Cw is the concentration profile at the gut wall.

 In terms of bioequivalence (BE). It is assumed that highly

permeable, highly soluble drugs housed in rapidly dissolving
drugs products will be bioequivalent .
 Dissolution data can be used as a surrogate for
pharmacokinetic data to demonstrate BE of two drug
products.
 Significance of BCS Classification
 The principles of BCS are widely applicable in development of new
drug products as the scientific approach for testing of waiver on
clinical study and bioavailability of drug and in regulatory approvals
of drug.
 BCS is used to establish equivalence in applications for brand and
generic medicinal products, variation, fixed combination, extensions.
 The BCS classifies immediate release (IR) solid oral dosage forms on
the basis of solubility and permeability parameters (when combined
with dissolution testing.
 The evolution of these properties can be performed in vitro-,
thereby avoiding expensive and time-consuming testing in humans.
 BCS is implemented by regulatory agencies to predict the in vivo
pharmacokinetic performance of drugs based on above mention
properties.
 The system is used to justify biowaiver or formal exemptions from
clinical BE and BA studies for given drug products.
Application of Preformulation
 Development of Solid Dosage forms :
 Now a days solid dosage forms are the most widely
marketed and administered drugs. Almost 70% of the
administered drugs are in solid states.
 Preformulation studies provide the drug safety, stability,
efficacy before converting into dosage form.
 Preformulation studies are important for selection of the
drug candidate itself, selection of formulation components.
 Preformulation studies essential for API and drug product
mfg process, deciding most appropriate container closure
system.
 It is also important for development of analytical method
of new drugs candidate and toxicological strategy.
 It influences on the route of administration, delivery
system and the drug activity.
 In addition solubility, salt form, melting point,
dissolution of the API is also studied.
 They influence on the dissolution rate of the API,
stability, bioavailability, degradation rate and purity.
 The solid state properties studied include particle size,
its distribution, its surface area and porosity.
 It also includes true density, flowability, API color,
polymorphism, electrostatic interaction
 Development of Liquid dosage form :
 Liquid dosage forms such as solution, suspension, emulsion,
syrups, elixirs etc essential pharmaceutical products which
involves a mixture of active drug components and excipients.
 As compared with the solid dosage forms, the drug
degradation is much rapid in solution forms.
 It is important to ascertain that the drug doesn’t degrade
when exposed to gastro-intestinal fluid. (gastric juice).
 In provide pH based stability study, using different
stimulating GI condition can be designed.
 Preformulation provide thorough understanding of the
physicochemical properties of drug substances and their
susceptibility to hydrolysis, solvolysis, oxidation,
recemization, polymerization and photodecomposition to
development of stable and efficacious liquid dosage form.
 Development of Parenteral dosage form :
 Preformulation studies for the development of parenteral
dosage form are proposed drug dose and drug
concentration, type of administration (injection or
infusion), Aq and Non Aq solubility’s, pH effects, oxidation
and light stability, buffer effects, container compatibility,
absorption, leachable and drug safety.
Impact of preformulation studies on Stability of Dosage
forms :
 Stability analysis is an area of great interest in
preformulation studies.
 It is a complex set of procedure performed on candidate
drug molecule before going to market.
 It provide intrinsic stability of new drug molecule to
improve the integrity of dosage form.
 And also prevent its physical chemical stability and
pharmacological effects.
 Physical stability of API’s includes changes in physical
appearance, color, odor, identity, optical rotation.
 Physical properties depends upon the temp and humidity.
 Stability studies help to establish how physical, chemical
and microbiological changes influence the effectiveness,
safety and stability of the final product.
 It also aid to recommend storage condition, shelf life of
drug, solid state stability, solution state stability analysis
and drug-excipients compatibility studies.
 According to the International Council on Harmonisation
(ICH) guidelines, stability testing carried out in different
conditions of temp and humidity for different periods.
Drug-excipients Compatibility Studies
 Excipients are substances which are included along with
the API in dosage forms.
 Most excipients have no direct pharmacological action but
are important for facilitating the administration, release of
active components and stabilizing API against degradation.
 However, inappropriate excipients can also give rise to
unintended effect which can affects the chemical nature
and stability and bioavailability of API and their
therapeutic efficacy and safety.
 Thus, this information generated is very useful to the
formulator in selecting appropriate excipients for a drug
product.
 In pharmaceutical products, drugs are indirect contact with
one or more of the excipients and therefore can interact to
undergo chemical reactions and physical interactions
under favorable conditions producing less active, inactive
or toxic product by adverse reactions.
 Preformulation concept includes drug-excipients
compatibility studies which focus on physical chemical and
therapeutically incompatibilities of the products.

Physical incompatibilities Chemical incompatibilities

Include change in physical form, like

Includes hydrolysis, oxidation,
color, odor, test, dissolution,
reduction, precipitation,
solubility, sedimentation rate,
recemization, undesirable reactions
liquefaction, phase separation or
between API and excipients etc
immiscibility
Thank You
 Bulk Density:
Apparent bulk density (g/cm3): Bulk drug powder is
sieved through 40 mesh screen.
 Weight is taken and poured into a graduated cylinder
via a large funnel. The volume is called bulk volume.
 Bulk density = Weight of the powder/Bulk volume
 Tapped density (g/cm3): Bulk powder is sieved
through 40 mesh screen. Weight is taken and poured
into a graduated cylinder. The cylinder is tapped 1000
times on a mechanical tapper apparatus. The volume
reaches a minimum – called tapped volume.
 Tapped density = Weight of the powder/Tapped
volume