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Pharmaceutical preformulation studies in formulation and development of

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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20 ISSN: 2278-6074

Review Article

Pharmaceutical Preformulation Studies in Formulation and Development of New

Dosage Form: A Review
Garima Verma*, Manoj Kumar Mishra

Shambhunath Institute of Pharmacy, Jhalwa, Allahabad, Uttar Pradesh-211012, India.

_______________________________________________________________________________________________________________________
Abstract:
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic
promise in animal models to warrant evaluation in man. These studies should focus on those
physicochemical properties of the new compound that could affect drug performance and
development of an efficacious dosage form. A thorough understanding of these properties may
ultimately provide a rational for formulation design or support the need for molecular
modification. This review article focus on the various preformulation factors which effect the
development of new dosage form like drug solubility, partition coefficient, dissolution rate,
polymorphic forms and stability. Every drug has intrinsic chemical and physical properties
which has been consider before development of pharmaceutical formulation. This property
provides the framework for drug’s combination with pharmaceutical ingredients.
Preformulation studies carried out by various research scientists are reviewed. Preformulation
studies conduct for newly synthesized compounds or extracted compound and it gives the
information regarding the degradation process, any adverse conditions relevant to the drug,
bioavailability, pharmacokinetics and formulation of similar compound and toxicity.
Preformulation studies strengthen the scientific foundation of the guidance, provide regulatory
relief and conserve resources in the drug development and evaluation process, improve public
safety standards, enhance product quality in the fabrication of dosage form. Objective of
preformulation study is to develop the elegant, stable, effective and safe dosage form by
establishing kinetic rate profile, compatibility with the other ingredients and establish Physico-
chemical parameter of new drug substances. Polymorphism having crystal and amorphous
forms shows different chemical physical and therapeutic description of the drug molecule.

Keywords: Preformulation, partition coefficient, dissolution rate, polymorphic

Received 06 Sept 2016 Received in revised form 21 Sept 2016 Accepted 23 Sept 2016

Corresponding Author:
Garima Verma,
Shambhunath Institute of Pharmacy, Jhalwa, Allahabad, Uttar Pradesh-211012, India.
Email: garima.srivastava2111@gmail.com, bmanojmishra@gmail.com
_________________________________________________________________________________________________________________________
INTRODUCTION
Before starting the preformulation studies, team consisting of representatives from the
we should know the properties of the drug, disciplines has responsibility for assuring
potency relative to the competitive that the compound enters the development
products and the dosage form, literature process in its optimum molecular form.
search providing stability and decay data, When the first quality sample of new drug
the proposed route of drug administration, becomes available, probing experiments
literature search regarding the formulation should be conducted to determine the
approaches, bioavailability and magnitude of each suspected problem area.
pharmacokinetics of chemically related If a deficiency is detected the project team
drugs. should decide on the molecular
Once a pharmacologically active modifications that would most likely
compounds has been identified, a project improves the drug properties. Salts,

Garima Verma et.al, IJPRR 2016;5(10) 12

International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
prodrugs, solvates, polymorphs or even
new analogs may emerge from these
modification efforts. The major areas of
preformulation research are following-
1. Bulk Characterization
Crystallinity and polymorphism
Hygroscopicity
Particle size
Bulk density
Powder flow properties
2. Solubility Analysis
Ionization constant-pKa
pH solubility profile
Common Ion Effect-Ksp
Thermal Effects
Solubilization
Partition Coefficient
Dissolution
3. Stability Analysis
Stability in Formulations
Solution Stability
pH Rate Profile
Solid State Stability
Bulk Stability
Compatibility
Bulk characterization- A drug candidate at
this stage had not all of its solid forms
identified, and there is a great potential for
new polymorphs to emerge. Bulk properties
for the solid forms such as particle size,
bulk density and surface morphology are
also likely to change during process
development.
Crystallinity and polymorphism: Elements
can exist in two or more different forms,
known as allotropes of that element e.g.
Carbon: diamond in cubic (tetrahedral
lattice arrangement) graphite in sheets of a
hexagonal lattice. Polymorphs show the
same properties in the liquid or gaseous
state but they behave differently in the solid
state. Different polymorphs of a compound
are in general different in structure and
properties in the same manner as the
crystals of two different compounds.
Furthermore polymorphism is remarkably
common particularly within certain
structural groups.
The phenomenon of polymorphism is quite
common among organic molecules, and
many drugs can crystallize into different
polymorphic forms [1-4]. Molecules
Polymorphic forms of drugs can prove
Garima Verma et.al, IJPRR 2016;5(10)
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interesting for drug developers because
their thermodynamic and physicochemical
properties, such as melting point, density,
stability and in particular solubility, may
offer an improvement on the original form.
Generally, the solubility of metastable
polymorphs is kinetically higher than that
of a thermodynamically more stable
polymorph [5], offering, at least in theory, a
solution to bioavailability problems.
Actually, it has been demonstrated that
differences between the solubility of one
polymorph and another are typically lower
than a factor of two [6] or more rarely of
five [7]. Thus, while a polymorph may offer
a slight improvement in solubility
compared to the original compound, this
benefit may be offset the fact that it is also
less stable than the original, and thus there
may be no advantage in choosing this
polymorph over the original compound.
Actually, metastable and more soluble
forms tend to convert into the more
thermodynamic stable form in a relatively
short time.
The presence of specific excipients, or
particular chemical and/or technological
processes may accelerate the transition to
the solid state [8, 9]. This transition may
proceed according to the relative
thermodynamic stability of metastable
forms.
Solvates, also inappropriately termed
pseudopolymorphs [10], are crystalline
solids containing within the crystal
structure either stoichiometric or
nonstoichiometric proportions of solvent.
When the incorporated solvent is water, the
solvate is called a hydrate. In general, it is
undesirable to use solvates for drugs and
pharmaceuticals, as the presence of organic
solvent residues may be toxic; regulations
for all the organic solvents in products for
human use establish specific limits to how
much daily exposure to residual solvent in
the formulated preparation is allowed. The
solubility and dissolution rate of a drug can
significantly differ for different solvates,
and in particular hydrates [11].
Hydrates may have a faster or slower
dissolution rate than the corresponding
anhydrous form, though more frequently,
the former are slower than the latter [12],
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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
perhaps because there are fewer sites of the
drug molecule available for interaction with
water during dissolution. A classic example
is theophylline anhydrate, which dissolves
faster than its hydrate form [13,14]. In
other cases, the hydrate form exhibits a
more rapid dissolution rate than its
anhydrous form: for example, erythromycin
dihydrate was found to exhibit a
significantly faster dissolution rate than
that of monohydrate and anhydrous forms
[15,16].
Glibenclamide has been isolated as pentanol
and toluene solvates, and these solvates
exhibited higher solubility and dissolution
rate than two non-solvated polymorphs
[17]. The physical stability of hydrates and
anhydrous forms strongly depends upon
the relative humidity and/or temperature
of the environment [18-20], and transitions
from one form to the other occur as a
consequence of variations in storage
conditions and/or technological treatments
[21]. In particular, anhydrous to hydrate
transitions can occur during dissolution at
the drug/medium interface and can affect
dissolution rate and perhaps bioavailability
[18].
Type of Polymorphism- There are two
types of polymorphs- enantiotropic
polymorphs and monotropic polymorphs.
ENANTIOTROPHS: - If one form stable over
certain pressure and temperature range,
while the other polymorph is stable over
different pressure and temperature range.
e. g., sulfur.
MONOTROPHS: - only one polymorph is
stable at all temperature below the melting
point, with all other polymorph being
unstable. glyceryl stearate, chloramphenicol
palmitate.
Pseudo polymorphism-The term pseudo
means false. Phenomenons in which solvent
molecules get incorporated into crystal
lattice of solid are known as solvates. This
solvates exist in different crystal form called
pseudopolymorphs and the phenomenon is
called as pseudopolymorphism. Also known
as hydrates when water is solvent. When
the potent synthetic estrogen ‘ethynyle-
stradiol’ is crystallized from the solvents
acetonitrile, methanol, chloroform and
saturated with water four different
Garima Verma et.al, IJPRR 2016;5(10)
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crystalline solvates are formed. Pseudo-
polymorphs can be differentiated from true
polymorphs by observing melting behavior
in silicon oil using hot stage microscopy.
Here in this technique pseudo polymorphs
evolve gas (steam or solvent vapors)
causing bubbling of the oil. While true
polymorphs merely melts, forming second
globular phase.
Hygroscopicity- Many drug substances,
particularly water soluble salt forms have a
tendency to adsorb atmospheric moisture.
Adsorption and equilibrium moisture
content can depend upon the atmospheric
humidity, temperature, surface area,
exposure and mechanism for moisture
uptake [22]. Deliquescent materials adsorb
sufficient water to dissolve completely, as is
observed with sodium chloride on a humid
day. Other hygroscopic substances adsorb
water because of hydrate formation or
specific site absorption. With most
hygroscopic material, changes in moisture
level can greatly influence many important
parameters, such as chemical stability,
flowability and compatibility.
To test for hygroscopicity, samples of bulk
drug are placed in open containers with a
thin powder bed to assure maximum
atmospheric exposure. These samples are
then exposed to arrange of controlled
relative humidity environment prepared
with saturated aqueous salt solutions [23].
Moisture uptake should be monitored with
various time intervals of handling (0 to 24
hrs) and storage duration (0 to 12 weeks).
Analytical methods for monitoring the
moisture level (i.e. gravimetry, TGA, Karl
Fischer titration or gas chromatography)
depends upon the desired precision and the
amount of moisture adsorbed on to the
drug sample.
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.
A light microscope with a calibrated grid
usually provides adequate size and shape
characterization for drug particles [24].
Sampling and preparation of the
microscopic slide must be performed
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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
carefully to obtain a representative
dispersion. In conjunction with light
microscopy, stream counter devices, such as
coulter counter and HIAC counter, often
provide a convenient method for
characterizing the size distribution of
compounds. Sieve methods are used
primarily for large samples of relatively
large particles (100 microns).
A more precise measurement of surface
area is made by Brunauer, Emmett and
Teller (BET) nitrogen adsorption, in which a
layer of nitrogen molecules is adsorbed to
the sample surface at -1960C. Once surface
adsorption has reached equilibrium, the
sample is heated to room temperature, the
nitrogen gas is desorbed and its volume is
measured and converted to the number of
adsorbed molecules via the ideal gas law.
Surface morphology may be observed by
scanning electron microscopy (SEM), which
serves to confirm qualitatively a physical
observation related to surface area. For
example, bulk lots of drug recovered by
different crystallization processes that have
been used in an attempt o improve yield
may result in surface morphologies that
provide greater area for surface relations
such as degradation, dissolution or
hygroscopicity.
Bulk Density-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, or formulation.
Usually bulk density is of great importance
when one considers the size of high dose
capsule product or the homogeneity of a
low dose formulation in which there are
large differences in drug and excipient
densities.
Apparently bulk density is determined by
pouring presieved bulk drug into a
graduated cylinder via a large funnel and
measuring the volume and weight. Tapped
density is determined by placing a
graduated cylinder containing known mass
of drug or formulation on a mechanical
tapper apparatus, which is operated for a
fixed number of taps (approx 1000) until
the powder bed volume reached a
minimum. Using the weight of drug in the
cylinder and this minimum volume, the
Garima Verma et.al, IJPRR 2016;5(10)
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tapped density may be computed. In
addition to tapped density true density is
also desirable. It can be computed by liquid
displacement method and gas displacement
method.
Powder Flow Properties-pharmaceutical
powders may be broadly classified as free
flowing or cohesive (non free- flowing).
Most flow properties are significantly
affected by changes in particle size, density,
shape, electrostatic charge, and adsorbed
moisture, which may arise from processing
or formulation [25]. As a result a free
flowing drug candidate may become
cohesive during development, thus
necessitating an entirely new formulation
strategy. Flow properties of powder can be
determine by the parameters like angle of
repose, Hausner’s ratio, Carr’s index and
compressibility of any powdered sample
The angle of repose can be defined as the
constant three dimensional angle measured
relatively to the horizontal base, assumed
by a cone-like pile of material formed when
the powder is passed through a funnel-like
container [26]. An angle of repose lowers
then 400, indicates good flowability,
conversely an angle of repose superior to
400 is an indication of cohesiveness [27, 28].
This method is very simple but has some
disadvantages. The powder experiences
segregation, consolidation or aeration,
which influence the cone formation. The
angle of repose is not considered for many a
good method to measure powder flow,
because is highly dependent on
experimental factors, since it is not an
intrinsic property of the powder [29].
However, it is still considered useful since it
is a simple method that gives the powder
tendency to flow and has an associated
general scale of flowability consistence with
the classification reported by Carr [28].
Another parameter used to evaluate the
flowability is the compressibility index (CI).
This index measures the tendency of a
powder to consolidate, and is calculated
according to Eq. (1) [28, 29]
CI = TD – AD/TD (1)
In Eq. (1), TD and AD represent the tapped
(or packed) and aerated bulk densities,
respectively. The aerated bulk density is
defined as the mass divided by the volume
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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
occupied by the powder when the particles
are not in direct contact with each other.
However, a more realistic definition can be
given by the density measured after the
powder been aerated and left to settle
gently. The tapped bulk density is obtained
after tapping the container enclosing the
aerated powder [27]. The compressibility
index has an inverse relation with
flowability, i.e. the more compressible is the
material the less flowable it will be [28]. A
powder with a compressibility index lower
than 20% is considered to have a good
flowability [30].
The Hausner ratio is defined as the ratio
between the tapped bulk density and the
aerated bulk density. This ratio is a useful
measure of cohesion reflecting particle
friction. With a Hausner ratio higher than
1.4, the powder is considered a cohesive
difficult to fluidize powder. Ratios lower
than 1.25 characterizes a free-flowing
powder [27].
Solubility Analysis- One important goal of
the pre‐formulation effort is to devise a
method for making solutions of the drug. A
drug must possess some aqueous solubility
for therapeutic efficacy. In order for a drug
to enter the systemic circulation to exert a
therapeutic effect, it must first be in
solution. Relatively insoluble compounds
often exhibit incomplete absorption. When
a solute dissolves, the substance's inter-
molecular forces of attraction must be
overcome by forces of attraction between
solute and solvent molecules. This involves
breaking the solute‐solute forces and the
solvent-solvent forces to achieve the
solute‐solvent attraction. It focuses on
drug‐solvent interactions that could occur
during the delivery of a drug candidate. For
example, orally administered drug should
be examined for solubility in simulated
gastric media. We need to perform
solubility analysis of a new drug to provide
a basis for later formulation work and can
affect drug performance. Drugs with an
aqueous solubility less than 1% (10 mg/ml)
will suffer from bio absorption problems.
Preformulation solubility studies include
determination of pKa, temperature
dependence, pH solubility profile, solubility
products, solubilization mechanism and
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rate of dissolution [31]. Analytical methods
that are useful for solubility measurements
include HPLC, UV spectroscopy, florescence
spectroscopy and gas chromatography. For
most drugs, reverse phase HPLC offers an
efficient and accurate means of collecting
solubility data. The commonly used solvent
for the determination of the solubility are
0.9% NaCl solution, 0.01M HCl, 0.1M NaOH
etc. The pH, temperature, ionic strength and
buffer concentration mainly affect the
solubility of the drug.
pKa determination: Determination of
dissociation constant for a drug capable of
ionization with in a pH range of 1 to 10 is
important since solubility, consequently
absorption, can be changed by changing in
pH. The Henderson Hasselbach equation
provides an estimate of the ionized and un-
ionized drug concentration at particular pH.
For acidic compounds:
pH = pKa + log [ionized drug] /
[unionized drug]
For basic compounds:
pH = pKa + log [unionized drug] /
[ionized drug]
For weakly acidic drug with pKa value
greater than 3, the unionized form is
present within the acidic contents of the
stomach, but the drug is ionized mainly in
the neutral media of the intestine. For basic
drugs such as erythromycin and papaverine
(pKa 8 to 9), the ionized form is
predominant in both the stomach and the
intestine.
A pKa value can be determined by variety of
analytical methods. Buffer, temperature,
ionic strength and cosolvent effect. The
preferred method is the detection of
spectral shifts by ultraviolet or visible
spectroscopy. A second method,
potentiometric titration offers maximum
sensitivity for compounds with pKa values
in the range of 3 to 10.
pH solubility profile and common ion
effect: The degree of ionization and
therefore, the solubility of acidic and basic
compounds depend on the pH of the
medium. The saturation solubility for such
compounds at particular pH is the sum total
of solubility of ionized and unionized forms
[32].
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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
In a saturated solution of a salt with some
undissolved solid, there exists equilibrium
between the excess solid and the ions
resulting from the dissociation of the salt in
the solution [33]. The addition of a common
ion reduces the solubility of the slightly
soluble electrolyte. This salting out(drug
precipitation) results from the removal of
solvent molecules from the surface of the
electrolyte by the hydration of the common
ion. Salting in larger anions (hydrotropes)
e.g. benzoates, salicylates can open the
water molecules allowing an increase in
solubility of poorly-water soluble drugs.
Example hydrochloride salts often exhibit
lower solubility in gastric juice due to the
abundance of the chloride ions.
To explore a common ion interaction, the
dissolution rate of a hydrochloride salt
should be compared in different media:
Water and 1.2% w/v NaCl, 0.05 M HCl and
0.9% w/v NaCl in 0.05 M HCl. It is useful in
the choice of a suitable salt form for the
proper dissolution and accordingly
enhanced absorption. Factors affecting
degradation rates are temperature, effect of
pH and others such as ionic strength,
co‐solvent, presence and absence of O2,
presence of antioxidants and presence of
chelating agent.
Effect of temperature: The solubility of
solute in a solvent is dependent on
temperature, nature of solute and nature of
solvent. The heat of solution represents the
heat released or absorbed when a mole of
solute is dissolve in a large quantity of
solvent. Most of the substances are
endothermic, absorbing heat in the process
of dissolution. For these substances, an
increase in temperature results in increase
in solubility. Exothermic substances give off
heat in the process of dissolution. The
solubility of such substances would
decrease with increase in temperature. Care
should be taken as heat may destroy a drug
or cause other changes in the solution. E.g.
on excess of heating the sucrose solution
converted into the invert sugar. Depending
on the type of reaction whether it is
endothermic or exothermic heat is either
absorbed or released e.g. mixture of
chloroform and acetone. The heat produced
by the solute- solvent interaction is so much
Garima Verma et.al, IJPRR 2016;5(10)
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greater than the heat necessary to separate
the molecules of acetone and chloroform,
which can be detected as rise in
temperature of the liquid.
Solubilization: The drug candidate with
either poor water solubility or insufficient
solubility for projected solution dosage
forms, preformulation studies should
include limited experiments to identify
possible mechanisms for solubilization. A
general means of increasing solubility is the
addition of a cosolvent to the aqueous
system. The solubility of poorly soluble
nonelectrolytes can often be improved by
orders of magnitude with suitable
cosolvents such as ethanol, propylene glycol
and glycerin [33]. These cosolvent
solubilize drug molecules by disrupting the
hydrophobic interactions of water at the
nonpolar solute/ water interfaces. The
commonly used and acceptable cosolvents
in formulation of aqueous liquids for oral
solutions are- ethanol, sorbitol, glycerin,
PEG. For parenteral products,
dimethylacetamide is widely used. But in
case of oral liquids its application is limited,
because of its objectionable odor and taste.
Cosolvent effects for dissociated drug
molecules are usually much less [34]. Some
poorly soluble drugs can be solubilized in
micellar solutions such as 0.01M Tween 20
or via molecular complexes as with caffeine
[35, 36]. These specific formulations are
usually not developed during the
preformulation phase.
Partition Coefficient: A measurement of a
drug’s lipophilicity and an indication of its
ability to cross cell membrane is the
oil/water partition coefficient in systems
such as octanol/water and
chloroform/water. The partition coefficient
is defined as the ratio of unionized drug
distributed between the organic and
aqueous phase at equilibrium.
Po/w = Coi l/ Cwater
For drug delivery, the
lipophilic/hydrophilic balance has been
shown tobe contributing factor for the rate
and extent of drug absorption [37, 38].
Dissolution [39]: The dissolution rate of a
drug is only important where it is the rate
limiting step in the absorption process. The
solubility of a drug exceeded to 1mg/ml at
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International Journal of Pharma Research & Review, Oct 2016;5(10):12-20 ISSN: 2278-6074

pH 7, no bioavailability or distinction of the drug in solution under these

related problems were to be expected. conditions the rate constant K1 is defined
Below 1 mg/ml such problems were quite by K1 = 0.62 D2/3 V1/6 W1/2
possible and salt formation could improve Where, V is the kinematic viscosity
absorption and solubility by controlling the W is the angular velocity of a rotating disc
pH of the microenvironment, independently of drug [40]
of the drug and dosage forms position Stability Analysis: Preformulation stability
within the GI tract. The dissolution rate of a studies are usually the first quantitative
drug substance in which surface area is assessment of chemical stability of a new
constant during dissolution is described by drug. Factor effecting chemical stability
the modified Noyes-Whitney equation. critical in rational dosage form design
dc/dt = DA/hv (Cs-C) include temperature, pH and dosage form
Where, D - Diffusion coefficient diluents. The method of sterilization of
h - Thickness of the diffusion layer at the potential product will be largely dependent
solid liquid interface on the temperature stability of the drug.
A-surface area of the drug exposed to Drugs having decreased stability at elevated
dissolution medium temperatures cannot be sterilized by
V- Volume of medium autoclaving but must be sterilized by
Cs- Concentration of a saturated solution of another means, e.g., filtration. The effect of
the solute in the dissolution medium pH on drug stability is important in the
C - Concentration of drug in solution at time development of both oral administration
t. must be protected from the highly acidic
t - Time environment of the stomach. Buffer
When dissolution is controlled solely by selection for potential dosage forms will be
diffusion the rate of diffusion is directly largely based on the stability characteristic
proportional to the saturated concentration of the drug. Accelerated stability study is
shown in (Table 1).
Table 1: Accelerated Stability Studies
Stress Conditions
Solid
Heat (00C) 4, 20, 30 ,40, 40/70% RH, 50 and 75
Moisture uptake 30,45,60,75,and 90% RH at RTa,b
Physical stress Ball milling
Aqueous Solution
pH 1 to 9 and 11 at RT and 370C. Reflux in 1 M HCl & 1 M NaOH
Lightc UV (254 and 366 nm)
Oxidationc Sparling with oxygen with at RT; UV may accelerate breakdown
a) RT is ambient room temperature can vary between 50 and 2500 C
b) Saturated solution of MgBr2 KNO2, NaBr, NaCl and KNO3 respectively.
c) At pH of maximum stability in simple aqueous solution.

Stability in Toxicology Formulation: It is subjected to an occasional shaking to check

often advisable to evaluate samples of the
toxicology preparations for stability and
potential homogeneity problems. Water,
vitamins, minerals, enzymes are present in
feed, which can severely be reduce the shelf
life of drug. Solution and suspension
toxicology preparations should be checked
for ease of manufacture and then stored in
flame-sealed ampoules at various
temperatures. In addition to chemical
stability, the suspension should be
dispersibility.
Solid state stability: Chemical instability
normally results from either of the
following reaction hydrolysis, oxidation,
photolysis and pyrolysis, Chemical
structure of the drug is the determination of
drug to either of these attacks. Esters and
lactase and to lesser extent, amides are to
prone to solvolysis, instauration or electron
rich centre in the structure make the
molecule vulnerable for free radical

Garima Verma et.al, IJPRR 2016;5(10) 18

International Journal of Pharma Research & Review, Oct 2016;5(10):12-20
mediated or photo-catalyzed oxidation.
Physical properties of drugs. Amorphous
materials are less stable than their
crystalline forms. Denser materials are
more stable to ambient stress.
Compatibility studies: The knowledge of
drug excipients interaction is useful for the
formulation to select appropriate
excipients. The described preformulation
screening of drug excipients interaction
requires only 5mg of drug in a 50% mixture
with the excipients to maximize the
likelihood of obscuring an interaction.
Mixtures should be examined under
nitrogen to ultimate oxidation and paralytic
effect at a standard heating rate on DSC,
over a temperature range, which will
encompass any thermal changes due to
both the drug and appearance or
disappearance one or more peaks in
thermograms of drug excipient mixtures are
considered of indication of interaction.
Solution stability: As compared with the
dry form, the degradation is much rapid in
solution form. It is important ascertain that
the drug doesn’t degrade when exposed to
GI fluid. The pH based stability study, using
different stimulator GI condition can be
designed. A poor solution stability of drug
may urge the formulator to choose a less
soluble salt form, provided the
bioavailability is not compromised.
CONCLUSION
Preformulation influences selection of the
drug candidate itself, selection of
formulation components, API & drug
product manufacturing processes,
determination of the most appropriate
container closure system, development of
analytical methods, assignment of API
retest periods the synthetic route of the API,
toxicological strategy. Preformulation
studies strengthen the scientific foundation
of the guidance, provide regulatory relief
and conserve resources in the drug
development and evaluation process,
improve public safety standards, enhance
product quality, facilitate the
implementation of new technologies, and
facilitate policy development and
regulatory decision making. Preformulation
studies give directions for development of
formulation in choice of drug form,
Garima Verma et.al, IJPRR 2016;5(10)
ISSN: 2278-6074
excipients, composition, physical structure,
helps in adjustment of pharmacokinetic and
biopharmaceutical properties. This review
article gives details of above studies which
prove that no pharmaceutical preparation
can be formulate without preformulation
studies.
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