LATIN SQUARE DESIGN

FACTORIAL DESIGN
LATIN SQUARE DESIGN
• As the word indicates, when English (Latin) alphabets are arranged in
a square manner, the design is called as Latin Square Design, For
instance, when a four point assay is conducted in the Frog’s rectus
abdominal muscle for identification of concentration of test, sqample,
the test is compared with standard solution having known
concentration.
• In the experiment, initially, dose response curves with standard
solution of different volumes (four volumes) are injected into the tube
containing the isolated tissue (connected to kymograph through a
lever).
• Likewise four response curves are obtained with four volumes of test
solution (here concentration of test solution is not know and has to
be determined.) Out of the four standard responses obtained, two are
selected (S1,S2) and two test responses (T1,T2) are selected. Later on
the same tissue, the solutions are injected as follows Table for
recording the responses.
S1 S2 T1 T2
The above design helps in
S2 S1 T2 T1
fulfilling the principle of
T1 T2 S1 S2
duplication i.e., repeating
several experiments on the same T2 T1 S2 S1

tissue helps in understanding the

variations that are practically
occurring.
Factorial Design

• In statistics, a full factorial experiment is an experiment whose design

consists of two or more factors, each with discrete possible values or
"levels", and whose experimental units take on all possible
combinations of these levels across all such factors.
• A full factorial design may also be called a fully crossed design. Such
an experiment allows the investigator to study the effect of each
factor on the response variable, as well as the effects
of interactions between factors on the response variable.
Contd.,
• For the vast majority of factorial experiments, each factor has only
two levels. For example, with two factors each taking two levels, a
factorial experiment would have four treatment combinations in total,
and is usually called a 2×2 factorial design.
• If the number of combinations in a full factorial design is too high to
be logistically feasible, a fractional factorial design may be done, in
which some of the possible combinations (usually at least half) are
omitted.
Contd.,
• ICH guidelines insists on Quality by Design (QbD) of experiments with
a strong rationale so as to ensure the drug product reach the market
at the earliest by doing logical, minimal and effective experiments.
• Factorial design is one of the approaches for conduct of experinents
at the Active Pharmaceutical Ingradient (API) synthesis, formulation
development, pre-clinical and clinical experiments.
• For optimizing the desired kleffect, to reach the optimized dependent
variable various independent variables are changed and experiments
are conducted to achieve the task to the nearest.
Contd.,
• For instance, for achieving the effect of high yield and highly pure API
it is necessary to establish temperature time of addition and contact
of the reactants, kind of catalysts,kind of combination of reactants,
sequence of addition of reactants etd., in case of achieving optimal
hardness of a tablet formulation, the factors such as pressure,
lubricant etc. play a key role.
• In case of dissolution the factors such as concentration of lubricant,
disintegrating agent etc., play a key role.
Contd.,
• A factor is a variable such as concentration of an agent, temperature, drug
treatment, diet. In an experiment, the number of factors may be more than
one and this depends on the objective and kind of experimental task.
• A factor can be qualitative assigned with a name and or quantitative assigned
with a number.
• It is believed that single factor designs fit for one –way ANOVA.
• In order to achieve the desired effect, every factor has to be optimized
individually and their combinations.
• In order to achieve optimized factor/s, every factor is studied at various levels,
and the levels of various factors that are giving optimized desired effect are
considered ideal.
• In a factorial design, the number of runs and trials depend on the
number of factors and number of levels of the factors. For instance, if
there are two factors and two levels, there are four numbers of runs
and trials.
• For instance, to achieve desired harness of tablet, two factors such as
pressure and lubricant are considered, and then we have the number
of runs (or trials) as follows
• When two ingredients such as A, B are taken into consideration to
their highest levels and their combination as dosage form resulted in
an additive effect, then the effect is biologically synergistic. If the
combination resulted into an effect less than the additive, then it is
interpreted that there is some interaction (say antagonist activity)
Desired pressure Lubricant
Effect/Factors

Hardness of tablet High High concentration

Hardness of tablet High Low concentration

Hardness of tablet Low High concentration

Hardness of tablet Low Low concentration

Advantages
• Many people examine the effect of only a single factor or variable. Compared to such one-
factor-at-a-time (OFAT) experiments, factorial experiments offer several advantages
• Factorial designs are more efficient than OFAT experiments. They provide more information
at similar or lower cost. They can find optimal conditions faster than OFAT experiments.
• Factorial designs allow additional factors to be examined at no additional cost.
• When the effect of one factor is different for different levels of another factor, it cannot be
detected by an OFAT experiment design.
• Factorial designs are required to detect such interactions. Use of OFAT when interactions
are present can lead to serious misunderstanding of how the response changes with the
factors.
• Factorial designs allow the effects of a factor to be estimated at several levels of the other
factors, yielding conclusions that are valid over a range of experimental conditions.