preformulation studies on bulk characterization.

1. PRESENTED BY,
MANGIRISH.R.TENDULKAR
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2.  Preformulation study is the foundation of developing
robust formulation.
 It can be defined as a phase of research & development
process for an investigation of physical and chemical
properties of new drug substance alone or in combination
with other excepients in order to development of safe
and effective dosage
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3.  The overall objective of preformulation testing is to
generate information useful to the formulator:
 To formulate stable and effective dosage form
 To increased drug stability
 To improve drug bioavailability
 Reduce drug excipient incompatibility
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4. Preformulation studies begins or shall be updated:
 immediately after the synthesis and initial toxicity
screening of a new drug.
 when a newly synthesized drug shows pharmacological
evidence that requires further evaluation in man
 when formulation and dosage form changes are required
 when solid form changes of DS are required
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5. 1. NATURE
2. COLOUR
3. ODOUR
4. TASTE
5. MELTING POINT
6. FLOW PROPERTIES
7. PURITY
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Organoleptic
properties
Particle size
and shape
Purity
Surface
area
Hygroscopicity
Bulk density

8. 1. Nature of the drugs can either be :
 Crystalline
 Amorphous.
CRYSTALLINE: Solids that have a definite geometrical shape
are known as crystalline Solids.
Amorphous: Solids that don’t have a definite geometrical shape
are known as Amorphous Solids
2. Nature of the drugs plays an important role in the
formulation.
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9. 
Crystalline solids have the following fundamentals properties.
1. They have characteristic geometrical shape.
2. They have highly ordered three-dimensional arrangements of
particles.
3. They are bounded by PLANES or FACES
4. Planes of a crystal intersect at particular angles.
5. They have sharp melting and boiling points.
Eg:
 Amorphous solids have the following properties:
1. In these solids particles are randomly arranged in three
dimension.
2. They don’t have sharp melting points.
3. Amorphous solids are formed due to sudden cooling of liquid.
4. Amorphous solids melt over a wide range of temperature
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10.  It is the inherent chemical structure relating to the certain level
of unsaturation.
 Intensity relates to the extent of unsaturation as well as the
presence of the chromophores.
 Some compounds may appear to have colour although it is
structurally saturated
 Eg: 1) off white:
2) cream yellow:
3) shiny: boric acid
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11.  One should also take into account of the compatibility of the
drugs with the excipients.
EG: amino acids containing drugs cant be used when lactose is
used as the diluent.
 Also take into consideration the colour of the drug with colouring
agents to be added to avoid mottling at the final stages of the
formlation
Eg: chinese paracetamol is yellowish in colour . It should be properly
mixed with the excipients so that there is no mottling problem.
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12.  The drug may exhibit an inherit odour charactertics of the major
functional group present
 It greatly affects the flavor of the preparation or the foodstuff.
Types of odour:
1. Pungent
2. Sulfurous
3. fruity
4. Aromatic
5. odourless
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13.  It is the most important parameter of the drug .
 Consider with respect to the patient compliance.
 If the taste is considered as unpalatable or bitter in taste it
should be suppressed by the addition of the appropriate flavors
and excipients & by sugar coating.
 EG: SWEET
SOUR
BITTER
SALTY
TASTELESS.
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14.  Purity studies are essential for further studies to be
carried out safely.
 Impurities may make a compound toxic or render it
unstable.
 TLC,HPLC,GC and Paper chromatography used.
 HPLC-Impurity Index(II), Homogeneity index(HI).
 DTA, gravimetric analysis and melting point by hot
stage microscopy are other techniques.
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15.  Impurity index(II):defined as the ratio of all
responses (peak areas) due to components other than
the main one to the total area response.
 Homogeneity index(HI): defined as the ratio of
response(peak area) due to main component to the
total response.
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16.  Differential thermal analysis(DTA)
 Thermogravimetric analysis(TGA)
 Differential scanning calorimetry(DSC)
 Powder X-Ray Differaction(PXRD)
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17.  Differential Scanning Colorimetry (DSC) and
Differential Thermal Analysis (DTH) measures the
heat loss or heat gain - resulting from physical or
chemical changes.
 Two types of processes
1) Endothermic : like fusion, boiling, sublimation,
vaporization, desolvation
2)Exothermic : like crystallization ,degradation
 Quantitative measurement of these process have
many application in preformulation study including
Purity, Polymorphism, solvation, degradation
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18.  Crystalline materials gives characteristics pattern –
by peaks in certain position & varying intensities
 different Polymorphs – different x-ray diffraction
pattern due to crystal lattice.
 Single crystal x-ray analysis provides precise
identification & description of a crystalline
substances.
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19.  All substances are transparent examined under
microscope – are either isotropic or anisotropic
 Isotropic substances do not transmit the light –
appears black – and have single refractive index. E.g.
Sodium Chloride
 Anisotropic substances – more than one refractive
index – appear bright and brilliant color – uniaxial and
biaxial
 Color depends upon – thickness of crystal and diff. in
refractive indices.
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20.  The pharmaceutical powders are classified as ---
 FREE FLOWING
 COHESIVE OR NON FREE FLOWING
 The powder flow are affected by the changes in –
 Density
 Particle Size
 Shape
 Electrostatic Charge
 Adsorbed Moisture
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Free flowing drug may become
cohesive and
necessitates an entirely new
formulation strategy

21.  A melting point can be used to identify a substance and to get
an indication of its purity.
 The melting point (or freezing point) of a solid is the
temperature at which the solid exists in equilibrium with its
liquid state under an external pressure of one atmosphere. Both
the melting point range (the interval between the beginning of
liquefaction and complete liquefaction) and the temperature of
complete liquefaction are valuable indicators of the purity of
the solid compound.
 A pure crystalline organic compound usually possesses
a sharp melting point and it melts completely over a narrow
temperature range of not more than 0.5-1.0o
C, provided good
technique is followed. The presence of even small amounts of
impurities usually produces a depression of the temperature at
which melting is complete and usually produces a
marked increase in the width of the melting point range.
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22.  Fill a melting point capillary tube with the sample of interest by
thrusting the open end into the powder several times
 In order to work the plug of solid material down to the sealed end of
the capillary, tap the sealed end on the table, or lightly draw a file (or
the jagged end of a tweezers) across the tube held loosely in the hand.
 Repeat the procedure until the tube contains a 3 mm column of densely
packed powder in the bottom.
 Place the thermometer in the apparatus so that the mercury container
is in level with the mouth of the circulator tube.
 Place the capillary in the melting point apparatus through one of the
side tubes so that the sealed end of the capillary is touching the front
of the mercury reservoir and begin to heat the apparatus with a micro
burner.
 Place the burner under the back end of the oil bath of the apparatus to
ensure the circulation of the silicone oil. Great care should be taken
about the rate of heating because the small amount of crystals in the
capillary can follow the temperature of the oil bath much faster than
the thermometer, so the temperature read a the time of melting is
several degrees below the true melting point.
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23.  Place the burner under the back end of the oil bath of the apparatus
to ensure the circulation of the silicone oil. Great care should be
taken about the rate of heating because the small amount of crystals
in the capillary can follow the temperature of the oil bath much
faster than the thermometer, so the temperature read a the time of
melting is several degrees below the true melting point.
 Place the burner under the back end of the oil bath of the apparatus
to ensure the circulation of the silicone oil. Great care should be
taken about the rate of heating because the small amount of crystals
in the capillary can follow the temperature of the oil bath much
faster than the thermometer, so the temperature read a the time of
melting is several degrees below the true melting point.
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Maker :Labindia model no.:MR-VIS
It is used to measure the melting point of the final
formulation or the API.

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26.  Preformulation studies have a significant part to play in
anticipating formulation problems and identifying logical path in
both liquid and solid dosage form technology.
 By comparing the physicochemical properties of each drug
candidate with in a therapeutic group, the preformulation
scientist can assist:
◦ the synthetic chemist to identify the optimum molecule,
◦ provide the biologist with suitable vehicles to elicit pharmacological
response and
◦ advise the bulk chemist about the selection and production of the
best salt with appropriate particle size and morphology for
subsequent processing.
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27.  LACHMAN L.,LIBERMAN H.,KAING J.;”The theory and practice
of industrial pharmacy”; 3 edition,p.n.-171-196,
 Introduction to pharmaceutics by atmaram pawar carrier
publications 2008
 www.authorstream.com
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