QBD Approach by HPLC method Developent and validation by antidiabatic drug

1. QBD APPROACH BY HPLC METHOD
DEVELOPMENT AND VALIDATION BY
ANTIDIABETIC DRUG
GUIDED BY : Miss.DISHA M.DHABARDE
MADE BY :SHIVANI H.JAMBHULKAR

2. INTRODUCTION
Pharmaceutical chemistry and Pharmaceutical Analysis are the branch of
chemistry which deals with the study of organic chemistry (molecules and
compounds) in combination with structural and chemical, biology and
pharmacology for producing pharmaceutical drugs and medicines and also
the series of process for identification, determination, quantitation, and
purification .
This is mainly used for the separation of the components from the mixture
and for the determination of the structure of the compounds respectively.
Analytical chemistry is the study of chemical. analysis through analytical
instruments. It can be used to identify, measure and quantify different
substances in a sample. It deals with the identification and quantification of
natural and artificial substances by physical (often spectroscopic)
properties.

3. HPLC
• High-performance liquid chromatography (or High pressure liquid
chromatography. HPLC) is a specific form of column chromatography
generally used in biochemistry and analysis to separate, identify,
and quantify the active compounds.
• HPLC mainly utilizes a column that holds packing material
(stationary phase), a pump that moves the mobile phase through
the column, and a detector that shows the retention times of the
molecules.
• Retention time varies depending on the interactions between the
stationary phase, the molecules being analyzed, and the solvent
used. The sample to be analyzed is introduced in small volume to
the stream of mobile phase and is retarded by specific chemical or
physical interactions with the stationary phase.

4. • The time at which a specific analyte elutes (comes out of the
end of the column) is called the retention time.
• Common solvents used include any miscible combinations of
water or organic liquids (the most common are methanol and
acetonitrile)
• Types Of HPLC
• Normal phase chromatography
• Reversed phase chromatography
• Ion exchange chromatography
• Size exclusion chromatography
• Bio affinity chromatography

5. RP -HPLC
• Reversed phase HPLC (RP-HPLC or RPC) has a non-polar stationary
phase and an aqueous, moderately polar mobile phase. RPC
operates the principle of on hydrophobic interactions, which result
from repulsive forces between a polar eluent, the relatively non-
polar analyte, and the non-polar stationary phase. The binding of
the analyte to the stationary phase is proportional to the contact
surface area around the non-polar segment of the analyte molecule
upon association with the ligand in the aqueous eluent.

6. QBD approach
• A QbD is defined as "A systemic approach to the method
development that begins with predefined objectives and
emphasizes product and process understanding and process
control, based on sound science and quality risk management .
• QbD aim to ensure the quality of medicine or product by
employing statistical analytical and risk management methodology
in design developed and manufacturing of medicine

7. • The QbD method was based on the understanding and
implementation of guidelines :
 ICH Q8 Pharmaceutical Development
 ICH Q9 Quality Risk Management, and
 ICH Q10 Pharmaceutical Quality System.
• QbD approach is used to HPLC method development-
 To achieve Quality, Safety, Efficacy
 High degree of robustness
 To increase process capability And decrease product variability and
 Defects enhancing product and process design understanding and
control.

8. • HPLC method development by Quality by design approach was
done as follows:
1)Selection of Quality Target Product Profile : The retention time,
theoretical plates, and peak asymmetry were identified as QTPP
2)Determination of Critical Quality Attributes:
The identification CQA typically takes place during the first stage of
process validation. This is the process design stage. This is the ideal
time to establish acceptable limits and ranges as well as establishing
protocols for measurement, data collection, and data analysis.

9. Method validation
• Method validation is a process used to confirm that the Analytical
procedures employed for specific test is suitable for its intended
used .
• According to ICH guidelines validation of analytical procedure :Text
and methodology ICHQ2(R1):The following parameter are taken
into consideration :
1) Analytical procedure
2)Specificity
3) Linearity
4)Accuracy
5) precision

10. 6)Limit of Detection: It is defined as lowest concentration of an
analyte in a sample that can be consistently detected.
7)Limit of Quantification: It is defined as lowest concentration of an
analyte in a test sample that can determine with acceptable
repeatability and accuracy.
8)Robustness : It is ability of a method to remain unaffected when
slight variations are applied.
9)Range

11. • Introduction to Disease:
Diabetes is a chronic disease that occurs either when the pancreas does not
produce enough insulin or when the body cannot effectively use the insulin it
produces.
Types:
Type 1:Insulin-dependent diabetes mellitus(IDDM)/juvenile onset diabetes
mellitus
Cause: Loss of B-cell function in type 1 diabetes
Treatment: Exogenous insulin to control hyperglycaemias
Type II: Noninsulin-dependent diabetes mellitus (NIDDM)/ maturity onset
diabetes mellitus
Cause: Lack of sensitivity of target organs to insulin
Treatment: Weight reduction, exercise, dietary modification, Hypoglycemic
agents, insulin therapy

12. Drug which are used for the treatment of diabetes are
• Metformin
• Lobeglitazone (LOBG)
• Glimepiride
• Glipizide(GLIDE)
• Pioglitazone(Piocare-30)
• Vildagliptin and Metformin HCL (Galvus Met)

13. Literature survey
1) Krunal Y. Patel et al,2021 has described that a quality-by-design
approach to HPLC method development. The analytical QbD
concepts were extended to the HPLC method development for
ceftriaxone sodium, and the final design space, a multivariant study
of several important process parameters such as the combination of
2 factors namely the mobile phase composition and pH of buffer at 3
different levels was performed. All the validated parameters were
found within the acceptance criteria. The validated method was
found to be linear, precise, accurate, specific, robust, and rugged for
determination of ceftriaxone sodium, The QbD approach to method
development has helped during method validation and transfer. The
statistical analysis of data indicates that the method is reproducible,
selective, accurate, and robust This method will be used further for
routine analysis for quality control in pharmaceutical industry.

14. 2)Vidhi Dave et al,2023; has developed a new, simple and sensitive
RP- HPLC method to analyzed Dapagliflozin and Metformin HCI in
bulk and in its tablet dosage form. At 227 nm. Dapagliflozin and
Metformin HCI were analyzed after applying the QbD approach. It
was found that the method was accurate, precise, reproducible,
and successfully applied to the pharmaceutical formulation as per
ICH guidelines.
3)Amit Vitthal Babar et al,9 september-2022 has developed a
simple, rapid, sensitive and economical stability-indicating
analytical method ,employing the systematic QbD-based approach
for quantification of Tamoxifen. Application of risk assessment
studies helped in prioritizing the factors, critically influencing the
method parameters, while factor screening and optimization
studies employing experimental designs finally embarked upon the
selection of CMPs/CPPs, thus facilitating the understanding of
relationship among CMPs/CPPs with CAAs.

15. 4)Athar Shamim et al,2023 has proposed a novel RP-HPLC-PDA
method, which was successfully developed and validated to
simultaneously estimate CPX and RUT in bilosomal nanoformulation
and shows therapeutic efficacy against antibiotic resistance by
disrupting bacterial biofilms. The use of AQbD and the Box− Banken
experimental design facilitates the significant improvement of
performance and the robustness of the method for the successful
separation and estimation of two analytes. The developed method
was found to be efficient and effective for routine analysis and
offered a quality result. All parameters were considered for method
validation, which were found to be in the acceptable range and
confirm that the proposed method is affordable, precise, robust, and
sensitive. These outcomes reveal that the proposed analytical HPLC
method can be used to simultaneously estimate CPX and RUT in
combined dosage forms for future investigations.

16. 5) Gadapa Nirupa et al,2 May 2012 has developed RP-HPLC method is
fast, reproducible, and simple. By adopting this method one can elute
all the three drugs in 5 minutes. Hence this method is definitely time
saving to enable the simultaneous estimation of glimepiride,
pioglitazone, and metformin. The proposed method is found to be
accurate, precise, linear, robust, and rugged.

17. Aim And objectives
 Aim
 Analytical Method Development and Validation for
Estimation of Antidiabetic Drug by RP-HPLC.
 Objectives
 To develop assay method for estimation of Antidiabetic drug by
using RP-HPLC.
 To develop a precise, accurate and simple validation method for
the estimation of drug by using High-performance Liquid
Chromatography.
 Study the Quality by design approach to method development and
validation of RP-HPLC.

18. Plan of work
 Estimation of Antidiabetic drug will be done by following method:
1)UV spectrophotometric method
2)HPLC method(High performance liquid chromatography method)
A)Literature survey
B) Selection of drug molecule
C)Method development of proposed method
• Wavelength selection and it's Detection
• Selection of mobile phase
• Preparation of Standard Calibration Curve
• Estimation of Drug in Marketed formulation by proposed method

19. D] Validation of Proposed Method
 Similarity factor
 System suitability
 Specificity
 Identification
 Interference
 Accuracy
 Precision
 Range
 Linearity
 Robustness

20. Reference
1. Introduction to pharmaceutical analysis by O'Reilly Media.
https://www.o'reilly.com
2.Ravisankar P, Navya CN, Pravallika D, Sri DN. A review on step-
by-step analytical method validation. IOSR J Pharm 2015;5:7-19.
3. HPLC : A SHORT REVIEW .JUNE 2010 Research Journal of
GLOBAL PHARMA TECHNOLOGY.
4.Sandipani R(2012)Quality by Design :A holistic concept of
building quality in pharmaceuticals.Int J Pharm Biomed Res
3:100-180.
5. VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND
METHODOLOGY Q2(R1).

21. THANK YOU