Development of Novel Stability Indicating Methods Using Liquid Chromatography

Reversed-phase high-performance liquid chromatography (RP-HPLC) has become the most widely used method for pharmaceutical analysis, as it ensures accuracy, specificity and reproducibility for the quantification of drugs, while avoiding interference from any of the excipients that are normally present in pharmaceutical dosage forms.

This book presents a simple methodology for developing stability-indicating methods and offers a ‘how-to guide’ to creating novel stability-indicating methods using liquid chromatography. It provides the detailed information needed to devise a stability-indicating method for drug substances and drug products that comply with international regulatory guidelines. As such, it is a must-read for anyone engaged in analytical and bioanalytical chemistry: professionals at reference, test, and control laboratories; students and academics at research laboratories, and scientists working for chemical, pharmaceutical, and biotechnology companies.  

1. Introduction

1.1. Introduction to analytical methods

1.2. History of Chromatography

1.3. High Performance Liquid Chromatography

1.3.1. High Performance Adsorption Chromatography

1.3.2. High Performance Partition Chromatography

1.3.3. High Performance Ion-Exchange Chromatography

1.4. Instrumentation of High Performance Liquid Chromatography

1.4.1. Mobile Phase Reservoir

1.4.2. Pumping System

1.4.3. Sample Injection System

1.4.4. Stationary Phase (Column)

1.4.5. Detector

1.4.6. Data System

1.4.7. Backpressure Regulator

1.5. Applications of HPLC

1.6. General Considerations for HPLC Method Development

1.6.1. Various Steps for Method Development

1.6.2. Optimization of the Method Development Parameters

1.7. HPLC Method Validation

1.7.1. Validation Parameters

1.7.1.2. Statistical Validation

1.8. System suitability

1.8.1. Retention Factor

1.8.2. Efficiency

1.8.3. Selectivity

1.8.4. Resolution

1.8.5. Tailing Factor

1.8.6. Asymmetry Factor

1.9. Stability Indicating Methods Development

1.9.1. Objective of Stability Studies

1.9.2. Stability Protocols

1.9.3. Degradation Pathways and Their Role in SIM Development

1.9.4. Need of Stress Testing in SIMs

2. Research Envisaged

2.1. Plan of Work

3. Drug(s) Profile

3.1. Ambroxol Hydrochloride

3.1.1. Description

3.1.2. Pharmacopoeial Specifications

3.1.3. Pharmacology

3.1.4. Adverse Effect

3.1.5. Drug Interaction

3.1.6. Doses

3.1.7. Brand Name

3.2. Cetirizine Hydrochloride

3.2.1. Description

3.2.2. Pharmacopoeial Specifications

3.2.3. Pharmacology

3.2.4. Interaction Studies

3.2.5. Toxicity

3.2.6. Side Effects

3.2.7. Adverse Effects

3.2.8. Dosage and Safety

3.2.9. Brand Name

3.3. Chlorpheniramine Maleate

3.3.1. Description

3.3.2. Pharmacopoeial Specifications

3.3.3. Pharmacological Action

3.3.4. Indications and Usage

3.3.5. Adverse Effects

3.3.6. Drug Interactions

3.3.7. Doses

3.3.8. Dosage Forms

3.3.9. Brand Names

3.4. Guaiphenesin

3.4.1. Description

3.4.2. Pharmacopoeial Specifications

3.4.3. Pharmacology

3.4.4. Adverse Effect

3.4.5. Drug Interaction

3.4.6. Doses

3.4.7. Brand Names

3.5. Paracetamol

3.5.1. Description

3.5.2. Pharmacopoeial Specifications

3.5.3. Pharmacological Action

3.5.4. Indications and Usage

3.5.5. Adverse Effects

3.5.6. Drug Interactions

3.5.7. Doses

3.5.8. Dosage Forms

3.5.9. Brand Names

3.6. Phenylephrine Hydrochloride

3.6.1. Description

3.6.2. Pharmacopoeial Specifications

3.6.3. Pharmacological Action

3.6.4. Indications and Usage

3.6.5. Adverse Effects

3.6.6. Contraindications

3.6.7. Overdose

3.6.8. Drug Interactions

3.6.9. Doses

3.6.10. Dosage Forms

3.6.11. Brand Names

3.7. Salbutamol Sulphate

3.7.1. Descriptions

3.7.2. Pharmacopoeial Specifications

3.7.3. Pharmacology

3.7.4. Adverse Effect

3.7.5. Drug Interaction

3.7.6. Contraindications

3.7.7. Doses

3.7.8. Brand Name

4. Materials and Methods

4.1. Instruments /Equipments /Materials /Reagents

4.1.1. Instruments

4.1.2. Column

4.1.3. Standards

4.1.4. Reagents and Solvents

4.1.5. Marketed Formulations of Drugs (Test Sample)

4.2. Method Development

4.2.1. Determination of Solubility of Drugs

4.2.2. Identification of Drugs

4.3. Optimization of Chromatographic Conditions for Method I, II & III

4.3.1. Optimization of Chromatographic Conditions for Method I

4.4. Method Validation

4.4.1. Preparation of Buffer for Mobile Phase

4.4.2. Standard and Sample Solutions Preparation

4.4.3. Specificity

4.4.4. Linearity and Range

4.4.5. Accuracy

4.4.6. Precision

4.4.7. Limits of Detection and Limit of Quantitation

4.4.8. Analysis of Tablets Formulations

4.4.9. System Suitability Test

4.5. Optimization of Chromatographic Conditions for Method II

4.6. Method Validation

4.6.1. Preparation of Buffer for Mobile Phase

4.6.2. Standard and Sample Solutions Preparation

4.6.4. Linearity and Range

4.6.5. Accuracy

4.6.6. Precision

4.6.8. Analysis of Tablets Formulations

4.6.9. System Suitability Test

4.7. Optimization of Chromatographic Conditions for Method II

4.8. Method Validation

4.8.1. Preparation of Buffer for Mobile Phase

4.8.2. Standard and Sample Solutions Preparation

4.8.3. Specificity

4.8.4. Linearity and Range

4.8.5. Accuracy

4.8.6. Precision

4.8.7. Limits of Detection and Limit of Quantitation

4.8.8. Analysis of Tablets Formulations

4.8.9. System Suitability Test

4.9. Forced Degradation Studies

4.9.1. Acid Degradation

4.9.2. Base Degradation

4.9.3. Oxidative Degradation

4.9.4. Thermal Degradation

4.9.5. Photo Degradation

5. Results and Discussion

5.1. Instrumentation and Chromatographic Conditions

5.2. Chemicals and Reagents

5.3. Identification of Drugs

5.4. Method Development

5.5. Method Validation

5.5.1. Specificity

5.5.2. Range

5.5.3. Linearity

5.5.4. Precision

5.5.5. Accuracy

5.5.6. The Limit of Detection and Limit of Quantitation

5.5.7. Analysis of Marketed Formulation

5.5.7. Analysis of tablets

5.6. Forced Degradation Studies

5.6.1. Acid Degradation

5.6.2. Base Degradation

5.6.3. Oxidative Degradation

5.6.4. Thermal Degradation

5.6.5. Photo Degradation

6. Summary and Conclusion

6.1. Summary

6.2. Conclusion

References

Dr. Mukesh Maithani, M.Pharma., Ph.D. in pharmaceutical sciences is a Scientist working with the Multidisciplinary Research Unit (ICMR), University Center of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India. He received the Young Scientist Award from the All India Medicos Society during its 26^th National Medical Congress in 2011 and has more than 12 years experience as a Research Scientist at Zydus Research Centre, Ahmadabad; and as a Senior Research Scientist at the Analytical Development Laboratory, Alembic Research Centre, Vadodara.

Dr. Maithani has made major contributions to pharmaceutical analysis, herbal formulations, and the standardization of drugs. His expertise includes drug discovery, novel analytical techniques, herbal excipients and drugs, targeted drug delivery etc. He has published more than thirty papers in national and international journals and conference proceedings, and is a co-author of seventeen books/book chapters. In addition, Dr. Maithani serves as a reviewer and advisory board member for several international and national journals.

Dr. Parveen Bansal, Ph.D. (Biochemistry), FRSM, FICA (USA), Joint Director, Baba Farid University of Health Sciences, has more than 23 years experience in various positions including Assistant Director/Founder Head of the National Institute of Ayurvedic Pharmaceutical Research. He represented India as a member of the 23^rd Indian Scientific Expedition to Antarctica. He holds three Young Scientist Awards, a Gold Medal from Gujarat Ayurveda University, Jamnagar, an Honorary Fellowship from the International Council of Ayurveda (USA), and a WHO In-country Fellowship from the World Health Organization. He has been nominated as a Member of the Screening Committee for the Cancer Consortium R&D Program, Department of Biotechnology, GOI, has published more than 170 research papers, 17 books and 46 book chapters, and serves as a reviewer or editorial board member for 35 high-impact international journals.