TERMS USED IN QUALITY TESTS

o Friability
It is the condition of being friable. It describes the tendency of a solid substance to chip or
break into smaller pieces under duress, handling or contact or rubbing (The opposite of friable
is indurate). Friability of any substance expresses the propensity or tendency for the substance
to reduce to finer particles (or chips) by the action of a small amount of (vibrational) force or
pressure, usually by rubbing or brushing up against other substances.

o Hardness
It is the measure or extent or degree a tablet can resist permanent shape deformation or change
when force is applied. Sometimes it is referred to as “breaking strength or force”. This is
because it is considered to be equal to the minimum pressure or force required to break a tablet
in a diametric compressional test.

o Disintegration
Disintegration refers to the mechanical break up of a compressed tablet into small granules
upon ingestion and therefore it is characterized by the breakdown of the inter-particulate bonds
which were forged during the compaction of the tablet. Disintegration test measures the ability
of a tablet to break down (in terms of disintegration time) into smaller particles or granules to
allow the active drug to dissolve (or be released) for absorption into the body.

Deaggregation of small particles (a process that exposes the active principle for dissolution) is
sometimes one of the rate-limiting processes for drug release. Because the tablets contain
particles that are in the colloidal size range, it may be assumed that the de-aggregation process,
at least qualitatively, is governed by Brownian motion and electrostatic and van der Waals
interactions.

Soluble tablets are uncoated or film-coated tablets that are intended to be dissolved in water
giving a clear or slightly opalescent solution. In the disintegration test of soluble tablets,
disintegration is expected to be within 3 minutes using water at room temperature (15–25° C).

o Dissolution
Dissolution is the process by which a substance forms a solution. Dissolution testing measures
the extent and rate of solution formation from a dosage form, such as tablet, capsule, ointment,
suspension etc. The dissolution of a drug is important for its bioavailability, and therapeutic
effectiveness.

o Particle size and shape measurement (analysis)

The particle size distribution of active ingredients and excipients is an important physical
characteristic of the materials used to formulate a pharmaceutical product. The size,
distribution and shape of the particles can affect bulk properties, product performance,
processability, stability and appearance of the end product. The link between particle size and
product performance is well documented with regards to dissolution, absorption rates and
content uniformity.

Reducing particle size can aid in formulation of poor water solubility (substance) product.
Particle size analysis (Laser Diffraction Particle Size Analyser) is an integral component of the
effort to formulate and manufacture many pharmaceutical dosage forms. The shape (crystalline
and amorphous) can also be key to solubility and predictability of absorption.
o Rate of Sedimentation (RS)
A suspension is a heterogeneous system containing dispersed solids of small size. These
particles can settle on standing. Therefore, the speed at which the settling of the particles occur,
is the RS or SR. The rate of sedimentation or settling of the suspended phase depends on
several factors which are under the control of the formulator or pharmacist. A Pharmaceutical
suspension is a coarse dispersion in which internal phase (therapeutically active ingredient) is
dispersed uniformly throughout the external phase (vehicle). We may have flocculated and
deflocculated suspension.

The rate of sedimentation is given by the approximate measurement of time and height of fall.

Sedimentation volume for flocculated suspensions: is the ratio of the

ultimate volume of sediment (Vu) to the original volume of sediment (VO) before settling.

Vu/ VO

o Stability of emulsion or cream

An emulsion or cream is a mixture of two or more liquids that are normally immiscible with
each other. Emulsion stability can be defined as the system's ability to resist changes in its
physicochemical properties over time. By definition, an emulsion contains tiny particles of one
liquid suspended in another. This is an example of an unstable emulsion. Stable emulsions can
be formed from two immiscible liquids when an emulsifier (surface active agent) is used.
Such emulsions do not separate out after a change in conditions like temperature or over time.

o Flowability
A simple definition of powder flowability is the ability of a powder to move, drift or flow in a
certain manner in a vessel or surface. By this definition, flowability is sometimes thought of as
a one-dimensional characteristic of a powder whereby powders can be ranked on a sliding scale
from free-flowing to non-flowing. A powder is called free-flowing if the particles do not stick
together. If particles are cohesive, they cling to one another to form aggregates. The
significance of cohesion increases with decreasing size of the powder particles; particles
smaller than 100 µm are generally cohesive. Also, cohesion can be increased by moisture.

o Clarity test
Clarity is the extent of the absence of particulate matter in a liquid formulation. It could be
considered to be the extent of transparency. The test is used for ampoules and vials of
parenteral products. Clarity testing is carried out to check the particulate matter in the sample.
In this test, transparent particles or white particles observed against the black background and
the black or dark particles observed against the white background

o Measurement of pH (by extension pKa)

This is a quantitative expression of the degree of acidity or alkalinity of a solution. It is
expressed on a logarithmic scale between 0 and 14 where 7 is neutral. Lower values are more
acidic and higher values, more alkaline. This is important for buffered liquid products.
NB: pH is equal to −log10 H, where H is the hydrogen ion concentration in moles per liter.

o Measurement of pKa
This is particularly important for the salt forms of active principles (API)
NB: pKa is the negative base-10 logarithm of the acid dissociation constant (Ka) of a solution.
pKa = -log10Ka
The lower the pKa value, the stronger the acid. For example, the pKa of acetic acid is 4.8,
while the pKa of lactic acid is 3.8. Using the pKa values, one can see lactic acid is a stronger
acid than acetic acid.

o Viscosity (rheological test)

Viscosity evaluation is a rheological test. It is a measure of a fluid's resistance to flow. It
describes the internal friction of a moving fluid. A fluid with large viscosity resists motion
because its molecular makeup gives it a lot of internal friction.

Rheology is defined as the study of flow and deformation of materials. It is a powerful tool that
can be used to characterize a broad spectrum of formulations or materials ranging from
solutions, polymer melts, gels, particulate system etc. It can also be used to provide information
and characterize microstructure of many materials. Rheological measurements can be
performed in either steady or dynamic mode (using shear stress in the form of force or
pressure).

Steady Shear Rheology: The steady shear measurement is performed by subjecting a sample to
a steady shear at a constant shear rate resulting in a generation of a shear stress. The
corresponding shear stress on the sample is measured using a torque transducer. The function
of the steady shear rate is referred to as viscosity.

Dynamic Rheology: This technique also called dynamic oscillatory flow involves the
application of a sinusoidally varying in the linear viscoelastic region. Dynamic rheology has
been used to characterize cellulose derivatives system providing important information such as
the sol-gel transition.

Based on the rheological characteristics a liquid formulation can either be Newtonian or non-
Newtonian.
Newtonian
When a fluid or liquid formulation shows the behavior that maintains a constant force of
resistance (viscosity) when a gradually increasing shear is applied, it is referred to as
Newtonian in nature.

non-Newtonian fluids
When a fluid or liquid formulation shows the behavior that decreases (thinning) or increases
(thickening) force of resistance (viscosity) when a gradually increasing shear is applied, it is
referred to as non-Newtonian in nature. The non-Newtonian fluids can be divided into:

1. Thixotropic: A thixotropic material will have shear-thinning behavior (decreasing force

of resistance) when a gradually increasing shear is applied. This is because the
orientation of the structure’s molecules or particles will change to align with the flow
direction.
2. Rheopetic: Rheopecty or rheopexy material is the rare property of some non-Newtonian
fluids to show a time-dependent increase in viscosity (shear-thickening behavior); the
longer the fluid undergoes shearing force, the higher its viscosity. Examples
of rheopectic fluids include gypsum pastes.