This document discusses the application of quality by design (QbD) approach in developing and validating a reverse phase high performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of antiretroviral drugs in pharmaceutical dosage forms. It provides background on HPLC, QbD, design of experiments (DoE), method development strategy using QbD, and validation parameters. The plan of work involves developing the RP-HPLC method using a QbD approach, validating the method per ICH guidelines, applying it to marketed formulations, conducting forced degradation studies, and finalizing documentation.

1. APPLICATION OF QUALITY BY DESIGN APPROACH IN RP-
HPLC METHOD DEVELOPMENT AND VALIDATION FOR
SIMULTANEOUS ESTIMATION OF ANTI-RETROVIRAL
DRUGS IN PHARMACEUTICAL DOSAGE FORM
by
CHANDU.CHATLAM.PHARM
Y18MPH301
Dept. Of Pharmaceutical Analysis

2. Contents:
Introduction
Quality by design
Drug profile
Literature survey
Aim and objective
Plan of work
Reference

3. INTRODUCTION
• Pharmaceutical analysis is defined as the application of analytical procedures used to determine the purity, safety
and quality of the drugs and chemicals. It includes both qualitative and quantitative analysis of drugs.
• Active Pharmaceutical Ingredient is defined as any component that provides pharmacological activity or other
effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure or any function
of the body of man or animals.
• Chromatography is a technique in which the separation of a mixture into individual components using a
stationary phase and a mobile phase.
• Based on the principle of separation chromatography classified into 2 types
1. Adsorption chromatography
2. Partition chromatography

4. • Factors affecting the choice of analytical methods:
a)The type of analysis required.
b)Problem arising from the nature of the material.
c) Possible interference from components of the material other than those of interest.
d) The concentration range, which needs to be investigated.
e)The accuracy required.
f) The facilities available.
g)The time required for complete analysis.
h)Similar type of analysis performed

5. HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
• HPLC instrumentation:

6. QUALITY BY DESIGN (QBD)
• ICH guidelines Q8 (R2) defines QbD as "A systematic approach to development that begins with predefined
objectives and emphasizes product and process control, based on sound science and quality risk
management".
• ICH guideline and QbD (ICH guideline Q8, 2012; ICH guideline Q10, 2012; ICH guideline Q9, 2012).
• FDA’s view of QbD is ‘‘QbD is a systematic approach to product and process design and development’
• Two key concepts can be introduced that further aid in implementation and understanding of QbD. The first
concept is “design space”. ICH Q8 (R2) defines it is the multidimensional combination and interaction
of input variables (e.g., material attributes) and process parameters that have been demonstrated to
provide assurance of quality’’
• Another important QbD concept is that of the “control strategy.” The purpose of the control strategy is to
ensure the final quality of the product. The control strategy is obtained from the process understanding gained
from modeling the design space.

7. DESIGNS
Designs are a collection of rows and columns that define the framework of the experiment.
The rows are the runs. The columns contain design information, components, factors, and
responses.
• There are four main study types:
1. Factorial
2. Response Surface
3. Mixture
4. Custom

8. DESIGN OF EXPERIMENT (DoE)
SCREENING DESIGNS
Design Merits Demerits
Fractional factorial design
(FFD)
 Suitable for large number of
factors and factor levels
 Evaluation of all possible
combination of interaction
• Effect cannot be uniquely
estimated
• Effects are confounded with
interaction term
• Difficult to construct
Placket-Burman Design (PBD)  Design with minimum
number of trials
• Design structure is complex
• Result in confounding of
effects, as number of
experiments is very less
Taguchi’s Hypothesis  Least number of
experiments
 Emphasizes a mean
performance characteristic
value
• Results obtain are only
relative
• Do not test all variables
combination

9. OPTIMIZATION
Response surface methodology
Design Merits Demerits
Box – Behnken design (BBD)  Economical alternative to CCD  Limited capability for
orthogonal blocking
Full factorial design (FD)  Efficient in estimating main
effects and interaction
 Maximum usage of data
 Reflection of curvature not
possible in two level design
 More experiment are required
Central composite design (CCD)  Require fewer experiments
 Combines the advantages of
FDs and star design
 Difficult to practice with
fractional values of alpha

10. flow chart of method development strategy using QbD Approach.

11. VALIDATION PARAMETERS
Characteristics Acceptance
Linearity R2≥0.9999, similar response ratios
Precision-System %RSD < 2%
Precision-Method %RSD < 2%
Precision- %RSD ≤ 2%
Repeatability/Reproducibility %RSD ≤ 2%
Accuracy FDA 98-102%, EPA 50-150%
Specificity No interference
Detection Limit >2 times base line
Quantitative Limit Signal-to-Noise =10:1
Range Concentration where data can be reliably

12. PLAN OF WORK
• Literature and survey
• Calibration of HPLC.
• Authentication of drug by UV, FT-IR .
• Method development of drug by RP- HPLC method using QbD
• Validate the developed analytical method of the drug (accuracy, precision linearity , range,
limit of quantification(LOQ),limit of detection(LOD) , robustness and system suitability) as
per ICH Q2 (R1) guide lines.
• Apply developed methods to the marketed formulation.
• Conduction of forced degradation studies which includes,
Acid-base hydrolysis
Oxidative study
Thermal study
Photo stability study
• Summarize the analytical methodology, finalize documentation.

13. • Thank U