Pharmaceutical Technology 1

Mohammad Mafruhi Sattar
Professor
Department of Pharmact
Jahgangirnagar University
PHARMACEUTICAL
TECHNOLOGY-I
PHR 315 3.0 Credit

Course Content
 Introduction: Definition, subject area, scope.
 Pre-formulation: Preliminary evaluation and molecular
optimization, bulk characterization of the material crystalinity
and polymorphism, thermal properties, hygroscopicity,
particle characterization, bulk density, powder flow
properties, solubility analysis, pKa determination, pH
solubility profile, effect of temperature, solubilization,
partition coefficient, dissolution, stability analysis, solution
stability, solid state stability.
 Dosage forms: Introduction, Definition, advantages,
disadvantages and classification of different pharmaceutical
dosage forms.
 Liquid dosage forms: Solution and elixirs, theory of
solution, different factors affecting solution process,
advantages and disadvantages, formulation considerations,

Course Content(cont’)
 Suspensions: Define, Advantages and disadvantages,
theoretical considerations, aggregated and dispersed
systems, formulation, manufacturing, stability,
evaluation and quality analysis, rheological
considerations, illustrative examples.
 Emulsions: Definitions, applications, advantages,
disadvantages, theory, formation, classification of
emulsifying agents, formulation, manufacturing, stability,
evaluation and quality analysis, rheological
considerations, illustrative examples.
 Semisolid (ointments, creams, pastes, gels):
Structure of skin, percutaneous absorption of drugs,
definition, classification of semisolid, classification of
ointment bases, formulation, manufacturing of

Course Content(cont’)
 Suppositories: Drug absorption from colon,
classification, formulation, manufacturing, packing and
testing of suppositories, suppository bases.
 Transdermal drug delivery system: Introduction,
advantages and disadvantages of transdermal drug
delivery, drug candidates for transdermal drug delivery,
transdermal therapeutic system, In vitro testing of
transdermal devices and drug candidates, transdermal
patch design, chemical and physical approaches to
transdermal delivery.
 Case Study: Diagnosis of dosage form related
problems and their management.
 Miscellaneous: Topic(s) covering the latest
advancement in the related fields may be introduced by
the respective course teacher.

“PREFORMULATION IS A BRANCH OF PHARMACY
WHICH DEALS WITH THE INVESTIGATION OF
PHYSICAL AND CHEMICAL PROPERTIES OF A
DRUG SUBSTANCE ALONE OR WHEN COMBINED
WITH EXCIPIENTS”
It is the characterization of the physical and
chemical properties of a drug, especially a newly
discovered drug.
– A case of learning before doing

Investigation of physico-chemical properties of the new
drug compound that could affect drug performance and
development of an efficacious dosage form”.
Preformulation commences when a newly synthesized
drug shows a sufficient pharmacologic promise in animal
model to warrant evaluation in man.
 The preformulation is the first step in the rational development
of a dosage form of a drug substance alone and when combined
with excipients.
 Objective :
To generate useful information to the formulator to design an
optimum drug delivery system.
The objective of this phase is the quantification of those
physical chemical properties that will assist in developing
a stable, safe and effective formulation with maximum
bioavailability.

 Preformulation is branch of Pharmaceutical science that
utilizes biopharmaceutical principles in the determination
of physicochemical properties of the drug substance.
 Prior to the development of any dosage form new drug , it
is essential that certain fundamental physical & chemical
properties of drug powder are determined .
 This information may dictate many of subsequent event &
approaches in formulation development.
 This first learning phase is called as preformulation.

Protocol for preformulation studies

Outline of principal areas of
preformulation research
Principal areas
Physico-
chemical
properties Bulk
characterisation
Stability analysis
Solubility
analysisOrganoleptic
properties
Particle size
and shape
Purity
Surface
area
Crystallinity and
polimorphism
Hygroscopicity
Particle size
characterization
Bulk density
Powder flow
properties
Ionization constant pka
PH solubility profile
Common ion
effect ksp
Thermal
effects
solubilization
Partition co-efficient
Dissolution
Solution stability
Solid state
stability
Bulk
stability
Compatibilty

IMPORTANCE OF
PREFORMULATION IN
PHARMACY
 It was introduced at 1960
 Preformulation testing is the first step in the rational
development of dosage form of a drug substance.
 Preformulation forms an indespensible part of the
inovator companey as well as generic companies.
 Preformulation testing generate information useful
to the formulator in developing stable and bioavilable
dosage forms.
 The necessity of preformulation is not only
acknowledged by most companies it is to a certain
extent prerequisite and forms back bone for R&D.

NEED FOR
PREFORMULATION
Preliminary evaluation
Molecular optimization
Suitability of excipients
Suitability of dosage form

INFORMATION THAT A PREFORMULATOR
OF PHARMACEUTICAL COMPANEY MUST
SUPPLY
 Solubility, dissolution, partition coefficient,
ionization constant, pka and kp values of the
drug.
 Crystall properties and polymorphism.
 Density, hygroscopicity, flowability, wetability and
stability studies.
 Micromeritics considerations such as – shape,
size, surface area, crystal habits etc..
 Compatibility with other compounds .
 Purity conformation by methods like-
HPLC, TLC, HPTLC ..

GOALS OF PREFORMULATION
 To establish the necessary physicochemical parameters of
new drug substances.
 To determine kinetic rate profile.
 To establish physical characteristics.
 To establish compatibility with common excipients.

Pre-formulation
 Preliminary evaluation
and molecular
optimization
 Bulk characterization of
the material crystalinity
and polymorphism
 Thermal properties
 Hygroscopicity
 Particle characterization
 Bulk density
 Powder flow properties
 Solubility analysis
 pKa determination
 pH solubility profile
 Effect of temperature
 Solubilization
 Partition coefficient
 Dissolution
 Stability analysis
 Solution stability
 Solid state stability.

Preliminary Evaluation
i. Compound identity.
ii. Formula and molecular weight.
iii. Structure.
iv. Therapeutic indications:
- Probable human dose.
- Desired dosage form(s)
- Bioavailability model
- Competitive products

Preliminary Evaluation (cont’d)
v. Potential hazards
vi.Initial bulk lots:
- Lot number
- Crystallization
solvent(s)
- Particle size range
- Melting point
- % volatiles
- observations
vii. Analytical methods:
- HPLC assay
- TLC assay
- UV/ Visible
spectroscopy
- Synthetic route
- Probable decay
products

Preliminary Evaluation (cont’d)
viii.Key dates
- Bulk scale-up
- Toxicology start date
- Clinical supply preparation
- IND filing
- Phase-1 testing

Preformulation Drug
Characterization in a Structured
Program

Program of Analytical
Preformulation

ORGANOLEPTIC PROPERTIES
COLOR ODOUR TASTE
OFF-WHITE PUNGENT ACIDIC
CREAM-YELLOW SULFUROUS BITTER
SHINY FRUITY SWEET
AROMATIC TASTELESS
ODOURLESS TASTELESS

COLOR
 Color is generally a function of a drug’s inherent
chemical structure relating to a certain level of
unsaturation.
 Color intensity relates to the extent of conjugated
unsaturation as well as the presence of chromophores.
 Some compound may appear to have color although
structurally saturated.

ODOUR
 The substance may exhibit an inherent odor
characteristic of major functional groups present.
 Odor greatly affects the flavor of a preparation or food
stuff.
 Taste:-
 If taste is considered as unpalatable, consideration is
to be given to the use of a less soluble chemical form
of the drug.
 The odour and taste may be suppressed by using
appropriate flavors and excipients or by coating the
final product.

PURITY
26
 Designed to estimate the levels of all known &
significant impurities & contaminates in the drug
substance under evaluation.
 Study performed in an analytical research &
development group.
 It is another parameter which allows for comparison
with subsequent batches.
 Occasionally, an impurity can affect stability.
e.g.
- Metal contamination
- Appearance

PURITY
27
 The techniques used for characterizing the purity of a
drug are the same as those used for other purpose in a
preformulation study.
 Thin layer chromatography is a wide ranging
applicability & is an excellent tool for characterizing
the purity.
 HPLC, paper chromatography & gas chromatography
are also useful.
 More quantitative information can be obtained by
using quantitative differential scanning colorimetry.

PARTICLE SIZE
26/02/201728
 Particle size is characterized using these terms :
i. Very coarse (#8)
ii. Coarse (#20)
iii. Moderately coarse (#40)
iv. Fine (#60)
v. Very fine (#80)

PARTICLE SIZE
29
 Particle size can influence variety of
important factors :
- Dissolution rate
- Suspendability
- Uniform distribution
- Penetrability
- Lack of grittiness

Methods to Determine Particle Size
30
Sieving
Microscopy
Sedimentation rate method
Light energy diffraction
Laser holography
Cascade impaction

04/05/2012KLE College of Pharmacy, Nipani.31
1. Sieving method :
 Range : 50 – 150 µm
 Simple, inexpensive
 If powder is not dry, the apertures get clogged.
2. Microscopy :
 Range : 0.2 – 100 µm
 Particle size can be determined by the use of
calibrated grid background.
 Most direct method.
 Slow & tedious method.

32
3. Sedimentation method :
 Range : 1 - 200 µm
 Andreasen pipette is used.
 Particle size is calculated by stoke’s law :
dst =
Where,
h = distance of fall in time, t
no = viscosity of the medium
ρs = density of the particles
ρ0 = density of the dispersion medium
g = acceleration due to gravity
18 η0 h
(ρs -ρ0) gt

04/05/2012KLE College of Pharmacy, Nipani.33
4. Light energy diffraction :
 Range : 0.5 – 500 µm
 Particle size is determined by the reduction in light
reaching the sensor as the particle, dispersed in a liquid
or gas, passes through the sensing zone.
 Quick & fast.
5. Laser holography :
 Range : 1.4 – 100 µm
 A pulsed laser is fired through an aerosolized particle
spray & photographed in three dimensional with
holographic camera, allowing the particles to be
individually imaged & sized.

34
6. Cascade impaction :
 The principle that a particle driven by an airstream will
hit a surface in its path, provide that its inertia is
sufficient to overcome the drug force that tends to keep
in it in airstream.

POWDER FLOW PROPERTIES
35
 Powder flow properties can be affected by change in particle
size, shape & density.
 The flow properties depends upon following-
1. Force of friction.
2. Cohesion between one particle to another.
 Fine particle posses poor flow by filling void spaces between
larger particles causing packing & densification of particles..
 By using glident we can alter the flow properties.
e.g. Starch, Talc.

Determination Of Powder Flow Properties
 By determining Angle Of
Repose.
 A greater angle of repose
indicate poor flow.
 It should be less than 30°.
& can be determined by
following equation.
tan θ = h/r.
where, θ = angle of repose.
h=height of pile.
r= radius.
Angle Of
Repose
( In degree)
Type Of Flow
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor
36

37
Measurement of free flowing powder by compressibility.
Also known as Carr's index.
CARR’S INDEX(%) =(TAPPED DENSITY – POURED DENSITY) X 100
TAPPED DENSITY
It is simple, fast & popular method of predicting powder
flow characteristics.

Carr’s Index Type of flow
5-15 Excellent
12-16 Good
18-21 Fair To Passable
23-35 Poor
33-38 Very Poor
>40 Extremely Poor
38

PARTICLE SHAPE
40
 Particle shape will influence the surface area, flow of
particles, packing & compaction properties of the
particles.
 A sphere has minimum surface area per unit volume.
 Therefore, these properties can be compared for
spheres & asymmetric particles, in order to decide the
shape.
 The following expression can be obtained:
Property Sphere particle
surface area πds
2 αs x dp
2
volume (1/6)πds
3 αv x dp
3
Cont…

PARTICLE SHAPE
41
 Therefore,
surface area = πds
2 = αs x dp
2
Volume = (1/6)πds
3 = αv x dp
3
 Solving for αs & αv by equating the appropriate properties
provides:
αs =
πds
2 & αv =
πds
3
 When particle shape is spherical, the ds = dp
 Thus, αs = π = 3.124 & αv = π/6 = 0.524
 Therefore, Shape factor = αs = 3.124 = 6
αv 0.524
dp2 6 dp3

SURFACE AREA
42
 Particle size & surface area are inversely related to each
other.
 Smaller the drug particle, greater the surface area.
 Specific surface is defined as the surface area per unit
weight (Sw) or unit volume (Sv) of the material.

SURFACE AREA
43
 Estimation of Sv :
Surface area of the particles
Sv =
Volume of particles
= n αs d2
n αv d3
= αs
αv d
 According to shape factor,
αs =
αv
 So, Sv = 6 / d.
6

SURFACE AREA
44
Estimation of Sw:
Sw = Surface area = Surface area
Weight density x volume
= Sv
ρ
= 6
ρ . d

Methods for determining
surface area
45
Adsorption method :
 Particles with a large specific surface are good
adsorbents for the adsorption of gases & of solutes
from solution.
 The volume of nitrogen gas, Vm, in cm3 that 1 g of
the powder can adsorb when the monolayer is
complete is more accurately given by using the
BET equation, however, which can be written as:
P = 1 + (b-1) . P
V(P0 – P) Vmb Vmb P0
Cont….

Methods for determining
surface area
46
 Where,
V = Volume of gas in cm3 adsorbed per gram of powder
at pressure P.
P = Pressure of the adsorbate, in mmHg.
Po= Saturation vapor pressure (monolayer)
Vm= Amount of vapor adsorbed per unit mass adsorbent,
when the surface is covered with monomolecular
layer
b = Constant that express the difference between the
heat of adsorption & heat of liquefaction of the
adsorbate (nitrogen).
Cont….

Molecular optimization
 Optimizing target interactions
 Optimizing access to the target
 Improvement of absorption
 Variation of alkyl or acyl substituents to vary polarity
 Varying polar functional groups to vary polarity
 Variation of N-alkyl substituents to vary pka
 Variation of aromatic substituents to vary pka
 Bioisosteres for polar groups
 Improving metabolism
 Steric shields
 Electronic effects of bioisosteres
 Stereoelectronic modification
 Metabolic Blockers
 Removal of susceptible metabolic groups
 Group Shifts
 Ring Variation

preformulation
research
I. Bulk
characterization
II.Solubility analysis
III.Stability analysis

BULK CHARACTERIZATION
It is needed to identify all the solid forms that may exist as a
consequence of the synthetic stage such as the presence of
polymorphs. Bulks properties such as particle size, bulk
density, surface morphology may be changed during the
development process and to avoid mislead predictions of
solubility and stability which depends on a particular crystalline
form.
 Changes in bulk properties of solid form such as particle
size, bulk density and surface morphology.
 Comprehensive characterization of all preformulation bulk
lots is necessary to avoid misleading predictions of stability
or solubility, which depend on a particular crystalline form.

BULK
CHARACTERIZATION
 Crystallinaty and polymorphism
 Hygroscopicity
 Fine partical characterization
 Bulk density
 Powder flow properties
 Compression properties
 Physical description

Characterization of solid forms
 Repeated spacing of atoms Randomly
placed atoms
in three dimentional structure or
molecules
 Have less energy Have high
energy
 Need less energy to break Need less
energy to break
crystalline form
 So solubility is less solubility is
high
Solid forms
Crystalline Amorphous

CRYSTALLINITY
 Crystal habit  Description of outer appearance of
crystal - platy, needle, tabular, prismatic, bladed, etc.
 Crystal lattice or internal structure  Molecular
arrangement with in the solid - cubic, tetragonal,
hexagonal, rhombic, etc.
CHARACTERIZATION OF A SOLID FORM:
 Verifying that the solid is the expected chemical
compound.
 Characterizing the internal structure and then
 Describing the habit of the crystal.

Outline of differentiating habits &
crystal chemistry of a compound

POLYMORPHISM
 Polymorphism is the ability of a compound to
crystallize as more than one distinct crystalline
species with different internal lattices.
Types of polymorphism:
 Enantiotropic e g : Sulfur
 Monotropic eg : Glyceryl stearates

Analytical methods for
characterization of solid forms
Method
Material
required/Sampl
e
Miroscopy 1 mg
Fusion methods (Hot stage microscopy) 1 mg
Differential scanning calorimetry
(DSC/DTA)
2 - 5 mg
Infra red 2 - 50 mg
X-ray powder diffraction 500 mg
Scanning electron microscopy (SEM ) 2 mg
Thermal gravimetric analysis (TGA) 10 mg

Pre-formulation
and molecular
optimization
and polymorphism
Hygroscopicity
 Particle characterization
 Bulk density
 Solubilization
 Dissolution

Hygroscopity
Many drug substances, particularly water soluble salt forms
have a tendency to absorb atmospheric moisture.
Adsorption and equilibrium moisture content can be
depend upon the atmospheric humidity, temperature,
surface area, exposure and the mechanism for moisture
uptake. e g :- Nacl
Tests for Hygroscopicity :
 Gravimetry
 Thermogravimetric analysis(TGA)
 Karl fischer titration or gas chromatography.

Pre-formulation
and molecular
optimization
and polymorphism
 Hygroscopicity
Particle characterization
 Bulk density
 Solubilization
 Dissolution

Fine particle characterization
Bulk flow, formulation homogeneity, and surface area controlled
processes such as dissolution and chemical reactivity are directly
affected by size , shape and surface morphology of the drug
particles.
Tests
 By light microscopy
 Stream counting devices(Coulter counter and HIAC counter).
 Brunauer , Emmett and Teller(BET) nitrogen adsorption for
surface area measurement.
 Each nitrogen molecule occupies an area of 16A2
 Surface morphology may be observed by SEM which serves to
confirm qualitatively a physical observation related to surface
area.

Bulk density
 Bulk density is the ratio between a given mass of a powder
and it’s bulk volume.
Bulk density= True volume+ Void volume
 Bulk density of a compound varies substantially with the
method of crystallization , milling or formulation. Once a
density problem is identified it is often easily corrected by
milling, slugging or formulation. Bulk density is of great
important in the size of a high dose capsule product or the
homogeneity of a low dose formulation in which there are
large differences in drug and excipient densities.

Powder flow properties
a. Free flowing
b. Cohesive
Measurement of free flowing powder is
Compressibility
% Compressibtility = ( ∫ t - ∫ 0 / ∫ t )* 100
∫ t - Tapped density
∫ 0 - Initial bulk density
Angle of repose are usually useless because of their lack
of precision.

Compressibility and Flow ability of
pharmaceutical excipients
%
Compressibility
Flow ability
5 - 15 Excellent
12 - 16 Good
18 - 21 Fair - passable
23 - 35 Poor
33 - 38 Very Poor
<40 Very, very poor

Solubility analysis
 Ionization constant – pKa
 Common ion effect- Ksp
 Thermal effects
 Solubilization
 Partition of co-efficient
 Dissolution

SOLUBILITY ANALYSIS
Preformulation solubility studies focus on drug-solvent systems that
could occur during the delivery of a drug to candidate.
eg:- A drug for oral administration should be examined for
solubility in media having isotonic chloride ion concentration
and acidic pH.
Analytical methods : Useful for solubility measurements
 HPLC
 UV spectroscopy
 Fluorescence spectroscopy
 Gas chromatography
For most drugs , RP-HPLC offers an efficient and accurate means of
collecting solubility data.

Determination of Solubility
Semiquantitative determination:
Solvent
(fixed volume)
Adding solute in small
incremental amounts
Vigorously
shaking
Undissolved
solute particles ?
Examine
visually
YesNo
Total amount
added up
Estimated solubility
“LAW OF MASS ACTION”

Accurately Quantitative determination:
Excess drug powder
150 mg/ml (15 %)
+ solvent
Ampul/vial
(2-5 ml)
Shaking at constant
temperature
(25 or 37 oC)
2 - 8 oC ?
Membrane filter
0.45 mm
Determine the drug
concentration in the
filtrate
Determine the drug
filtrate
Determine the drug
filtrate
Membrane filter
0.45 mm
Membrane filter
0.45 mm
Same
concentration ?
The first few ml’s of the filtrates should be
discarded due to possible filter adsorption
Solubility
48 hr
72 hr
? hr

pka Determination
Determination of dissociation constant of a drug.
Tested with in a pH range of 1-10.
Henderson- Hasselbalch equation provides an
estimate of the ionized and un-ionized drug
concentration at a particular pH .
For acidic compounds;
pH = pka + log [ionized drug/un-ionized drug]
For basic compounds;
 pH = p ka + log[un-ionized drug/ionized drug]
Analytical methods:
 The preferred method is the detection of spectral shifts by Ultraviolet or
visible spectroscopy.
 Potentiometric titrations.

Excess drug
powder
Stir in beaker
with distilled
water
Continuous
stirring of
suspension
Add
acid/base
Measure
pH of
suspension
Determine the
concentration
of drug in
the filtrate
SOLUBILITY pH
Filter Stirring
pH-Solubility Profile

 Poorly-soluble weakly-acidic drugs:
pH = pKa + log [(St - So)/So] (2)
 Poorly-soluble weakly-basic drugs:
pH = pKa + log [So/(St - So)] (3)
where
So = solubility of unionized free acid or base
St = total solubility (unionized + ionized)

Effect of Temperature
 The heat of solution, ∆ Hs represents the heat release
or absorbed when a mole of solute is dissolved in large
quantity of solvent.
 Endothermic
 Exothermic process
Tested for temperature range 5⁰C, 25⁰C,37⁰C and
50⁰C.
 In S= -∆ Hs /R (1/T)+C
S= molar solubility at temp. T(Kelvin)
R= gas constant

Solubilization
 Limited experiment to identify possible mechanism
for solubilization.
 Addition of co-solvent to aqueous system.
eg:- Ethanol , Propylene glycol, Glycerin.

Partition Co-efficient
 Measurement of a drug's liphophilicity .
 Contains Octanol /Water and Chloroform/Water systems.
Ratio of un-ionized drug distributed between the organic and
aqueous phases at equilibrium .
 Po/w = (Coil/ Cwater) equilibrium
 Provides liphophilic / hydrophilic nature of the drug .

Dissolution
 Dissolution experiment can help to identify potential
bioavailability problems.
 Dissolution can be controlled by several
physicochemical properties including chemical form,
crystal habit, partical size, solubility, surface area,
and wetting properties .
Noyes-Whitney equation for finding out dissolution rate
dc/ dt =DA/ hV (Cs-C)
D - Diffusion co-efficient
h- thickness of the diffusion layer at the solid-liquid
interface
A-surface area of drug exposed to dissolution media
V-volume of media
Cs-concentration of a saturated solution of the solute in
the dissolution medium at experiment temperature

Dissolution Apparatus
Type-1 Paddle
Type-2 Basket
Type-3 Reciprocating cylinder
Type-4 Flow through cell
Type-5 paddle over disc
Type-6 Cylinder
Type-7 Reciprocating through holder

Stability analysis
 Stability in toxicology formulations
 Solution state stability
 pH rate profile
 Solid state stability
 Bulk stability
 Compatibility

Stability analysis
1 st quantitative assessment of chemical stability of
a new drug
It includes
 solution
 solid state experiment under conditions
typical for the handling, formulation,
storage and administration of a drug
candidate
Method of testing: HPLC

Stability in toxicology
formulations
 Evaluate samples of the toxicology preparations for
stability and potential homogeneity problems.
 Usually a drug is administered to the animals in their feed
or by oral gavage of a solution or suspension of the drug
in an aqueous vehicle.
 Water, vitamins, minerals(metal ions ), enzymes present
in feed, which can severly reduce the shelf-life of a drug.
 Solution and suspension toxicologic preparations should
be checked for ease of manufacturing and then stored in
flame-sealed ampules at various temperature.

Solution stability
Objective: Identification of conditions necessary to
form a stable solution.
 These studies should include the effects of pH,
ionic strength, co-solvent, light, temperature and
oxygen.
 Solution stability investigations confirm decay at
the extremes of pH and temperature.
eg:- 0.1N Hcl , Water and 0.1N NaoH all at 90⁰C .

Solution stability testing
 Prepare stability solutions.
 Pour it in flint glass ampules, flame sealed to
prevent evaporation.
 Stored at constant temperature.
 Some ampules may be stored at a variety of
temperature to provide data for calculation.

Solution stability testing (cont’d)
Other Tests:
 Light stability test.
 Oxidation test.
i. With an excessive headspace of oxygen.
ii. With an excessive headspace of an inert gas Helium, nitrigen.
iii.With an inorganic anti-oxidant sodium metabisulfite.
iv. With an organic anti-oxidant Butylated hydroxy toluene (BHT).
Finally an Arrhenius plot is constructed by plotting the logarithm of the absolute
temperature.
InK = - Ea /R(1/T)+C
Ea - activation energy
- Ea /R- from slope
C- constant of integration
R- gas constant

Solid state solubility
Objective: Identification of stable storage conditions for drug
in the solid state and identification of compatible excipients
for a formulation.
Tests:
 DSC or IR analysis for the detection of polymorphic
changes.
 In case of surface discoloration due to oxidation or reaction
with excipients , surface reflectance measurements on
tristimulus or diffuse reflectance equipment may be more
sensitive than HPLC assay

DETERMINING BULK STABILITY
PROFILE FOR A NEW DRUG
CANDIDATE
Storage condition 4 Weeks 8 Weeks 12 Weeks
5⁰C-Refrigerator
22⁰C-Room temperature
37⁰C-Ambient Humidity
37⁰C/75%RH
Light box
Clear glass
Amber glass
Yellow-Green glass
No exposure(control)
-Oxygen headspace
-Nitrogen headspace
70⁰C--Ambient Humidity

Formulation Recommendation
 Upon completion of preformulation evaluation of a
new drug candidate, it recommended that a
comprehensive report be prepared highlighting
problems associated with this molecule
 These Reports re extremely important in preparing
regulatory documents

Conclusion
 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.

Pharmaceutical Technology 1

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