Table of Contents

Table of Contents

Cover Page and Title Page………………………………………………………....…i

Certificate………………………………………………………………………………..ii
Declaration………………………………………………………………………………iii
Acknowledgements………………………………………………………………….....iv
Table of Contents………………………………………………………………………vi
List of Tables……………………………………………………………………………xi
List of Figures………………………………………………………………………….xiii
List of Symbols, Abbreviations, and Nomenclatures……………………………...xvi
Structured Abstract…………………………………………………………………..xviii
Graphical Abstract……………………………………………………………………..xx

1  INTRODUCTION AND REVIEW OF LITERATURE .................................. 1 

1.1  Introduction to Orthostatic Hypotension: ..................................................... 1 

1.2  Mechanism ................................................................................................. 1 

1.3  Factors that can contribute to orthostatic hypotension................................ 2 

1.4  Drug treatment ............................................................................................ 2 

1.5  Introduction of Modified Release Dosage Form .......................................... 3 

1.5.1  Factors affecting Modified Release Dosage Form: .......................................................... 4 

1.5.2  Types and Mechanism of Sustain Release System ........................................................ 4 

1.6  Extended Release Polymers ...................................................................... 5 

1.6.1  Factors to be considered while selecting polymer ........................................................... 5 

1.6.2  Ideal requirements for polymers....................................................................................... 6 

1.6.3  Various Types of polymers............................................................................................... 6 

1.7  Drug Profile ................................................................................................. 7 

1.8  Introduction of Quality by Design ................................................................ 8 

1.8.1  Advantages ...................................................................................................................... 8 

1.9  Review of the literature related to drug substance ...................................... 9 

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1.10  Literature review for modified release technique 1 ................................ 11 

1.11  Literature review for modified release technique 2 ................................ 19 

2  OBJECTIVES .......................................................................................... 29 

3  MATERIALS AND METHODS ................................................................ 30 
3.1  Modified release bilayer tablet formulation of MDH by QbD approach ..... 30 
3.1.1  Drug-substance characterization ................................................................................... 30 

3.1.2  Drug-excipient compatibility studies ............................................................................... 32 

3.1.3  In-process and finished product characterization methods ........................................... 34 

3.1.4  Formulation of Bilayer modified release formulation of MDH ........................................ 36 

3.2  Modified release capsule formulation of MDH by QbD approach ............. 55 
3.2.1  Drug-substance characterization ................................................................................... 55 

3.2.2  Drug-excipient compatibility studies ............................................................................... 55 

3.2.3  Formulation development............................................................................................... 56 

3.2.4  Initial Risk Assessment of the Formulation Variables of Polymer Coated Pellets ......... 64 

4  RESULTS AND DISCUSSION ................................................................ 72 

4.1  Pre-formulation studies/Preliminary studies of Modified release bilayer tablet
formulation of MDH by QbD approach ................................................................ 72 
4.1.1  Physical Characterization............................................................................................... 72 

4.1.2  Drug identification/detection FTIR Spectroscopy ........................................................... 72 

4.1.3  Calibration curve of MDH by HPLC Method. ................................................................. 74 

4.1.4  HPLC chromatograph of MDH ....................................................................................... 75 

4.1.5  Drug excipient compatibility study .................................................................................. 78 

4.1.6  Formulation development............................................................................................... 86 

4.1.7  Discussion of the product development ....................................................................... 103 

4.1.8  Summary ...................................................................................................................... 104 

4.2  Modified release formulation of MDH capsules by using quality by design

approach. ......................................................................................................... 105 
4.2.1  Drug-substance characterization ................................................................................. 105 

4.2.2  Drug-excipient compatibility studies ............................................................................. 105 

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4.2.3  Formulation development............................................................................................. 111 

4.2.4  Discussion of the product development ....................................................................... 135 

5  SUMMARY AND CONCLUSION .......................................................... 138 

6  REFERENCES ...................................................................................... 140 
7  LIST OF PUBLICATIONS ..................................................................... 145 
7.1  Publication-1 ........................................................................................... 145 

7.2  Publication-2 ........................................................................................... 146 

7.3  Presentation-1 ........................................................................................ 147 

7.4  Presentation-2 ........................................................................................ 148 

8  PLAGIARISM REPORT ........................................................................ 149 

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