DECLARATION

I, Muhammad Ayub Naveed S/O Muhammad Naveed Ashraf, M.Phil.

Scholar of the College of Pharmacy, University of Sargodha, hereby declare that this

research work entitled “Design and In-Situ Evaluation of Taste Masked

Orodispersible Tablets of Cyclobenzaprine Hydrochloride” and the contents of

thesis are the product of my own research and no part has been copied from any

published source (except the references, standard mathematical or genetic models

/equations /formulas /protocols etc.). I further declare that this work has not been

submitted for award of any other degree /diploma. The University may take action if

the information provided is found inaccurate at any stage.

Signature _____________________

Name: Muhammad Ayub Naveed

Registration No: Registration No. 14F-US-36-08

Roll No: 14MPHIL(PHARM)14015

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 CERTIFICATE OF APPROVAL

This is to certify that this thesis entitled “Design and In-Situ Evaluation
of Taste Masked Orodispersible Tablets of Cyclobenzaprine
Hydrochloride” submitted by Mr. Muhammad Ayub Naveed is accepted in
its present form by the College of Pharmacy, University of Sargodha, Pakistan,
as satisfying the partial requirement for degree MASTER OF PHILOSOPHY
IN PHARMACEUTICS.

Internal Examiner:
____________________________
Prof. Dr. Humayun Riaz
Professor, Faculty of Pharmacy,
Lahore College of Pharmaceutical
Sciences

Co-Supervisor:
____________________________
Dr. Daulat Haleem Khan
Assistant Professor, Faculty of
Pharmacy, Lahore College of
Pharmaceutical Sciences

External Examiner:
____________________________
Dr. Fatima Rasool
Assistant Professor, College of
Pharmacy, University of the
Punjab, Lahore
Principal:
____________________________
Dr. Saira Azhar
Principal, College of Pharmacy,
University of Sargodha, Sargodha
Dean:
____________________________
Prof. Dr. Sajid Bashir
Dean, College of Pharmacy,
University of Sargodha, Sargodha
Student:
____________________________
Muhammad Ayub Naveed
14MPHIL(PHARM)14015
Registration No. 14F-US-36-08

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 ACKNOWLEDGEMENTS

Foremost I bow to ALMIGHTY ALLAH, Who has enlightened our minds and
hearts with faith and guided us to the right path, the path of wisdom, perspicacity and
sophistication. All respects, blessings and love to the last Holy Prophet Hazrat
MUHAMMAD ‫ ﷺ‬, who enabled me to recognize Creator and His creations and
changed me from man to Muslim by teaching, “Seek knowledge from cradle to grave.”
I dedicate my all research and efforts to my Grandfather Muhammad Ashraf
Fazliah (late), a Sufi soul, Pharmacist by profession with the heart of an Engineer.
Without his support, encouragement and guidance I may not able to reach my goal. I
deem it a great honor and no word is too eloquent to express my sense of gratitude to
him.
I would like to express my gratitude to my supervisor Prof. Dr. Humayun Riaz
for his overall direction and ongoing support. His door is always open for discussions.
I am greatly appreciative of his expertise and guidance without which this project would
not have been possible.
I appreciate the affectionate and kind guidance of Prof. Dr. Sajid Bashir, Dean,
College of Pharmacy, University of Sargodha during entire studies and research work
right from topic selection till end.
I offer my sincerest gratitude to my co-supervisor, Mr. Daulat Haleem Khan,
Assistant Professor, Mr. Umair Ikram Dar, Assistant Professor, and Mr. Izaatullah
Khan, Assistant Professor Lahore College of Pharmaceutical sciences who has
supported me throughout my thesis with his patience and knowledge.
I have appreciated the collaboration of my colleagues, Rana Ihsan ul Haque
Ather, Muhammad Salman Azam, Sadia Altaf, Dr. Ghayour Ahmed, H.M. Asif Iqbal,
Saleem Mansoor, Ghazanfar Ali, Shaheer Butt, Arslan Tariq, Ahmad Raza Shahid and
Hamza Butt.
I express my heartfelt gratitude to my father Muhammad Naveed Ashraf,
mother, my brother Ibad-ur-Rehman, my sisters, my loving and caring wife, my son
and daughter & and all other family members. Their unlimited love and affection served
me a beacon of light. It is through their benevolent help and wholehearted prayers that
enabled me to complete my studies. I am also indebted to all those people who prayed
for my success.

Muhammad Ayub Naveed

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TABLE OF CONTENTS

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Serial No. Contents Page No

1. Chapter 1: Introduction 01

1.1 Introduction 02

2. Chapter 2: Literature Review 08

2.1. Cyclobenzaprine hydrochloride 09

2.2. Method of preparation of orodispersible tablets 11

2.3. Advantage of orodispersible tablets 15

2.4. Taste masking 16

2.5. Aim & Objective 18

3. Chapter 3: Material & Method 19

3.1. Chemicals 20

3.2. Equipments 21

3.3. Method of manufacturing 21

3.4. Evaluation of orodispersible tablet 24

3.4.1. Physical test of Powders 24

3.4.1.1. Angle of repose 24

3.4.1.2. Bulk density & Tapped density 25

3.4.1.3. Compressibility index 25

3.4.1.4. Hausner’s ratio 26

3.4.2. Physical Tests of Tablets 27

3.4.2.1. Weight variation 27

3.4.2.2. Thickness and length 27

3.4.2.3. Impact durability test (friability) 27

3.4.2.4. Tablet Hardness 27

3.4.2.5. Disintegration time 28

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3.4.2.6. Wetting time 28

3.4.2.7. Water absorption ratio 28

3.4.2.8. Dissolution test 29

3.4.3. Drug Identification tests 30

3.4.3.1. FT-IR spectrum of pure drug and different formulations 30

3.4.3.2. Determination of Cyclobenzaprine Hydrochloride by 30

HPLC method as per United States Pharmacopoeia

3.4.3.3. Scanning Electron Microscopy (SEM) 31

3.4.3.4. X-ray diffraction of powder (XRPD) 31

3.4.3.5. Tongue response for in-vivo evaluation of taste masking 32

4. Chapter 4: Results 33

4.1. Evaluation of Orodispersible Tablet 34

4.1.1. Physical test of Powders 34

4.1.2. Weight variation 34

4.1.3. Thickness and length 35

4.1.4. Impact durability test (friability) 35

4.1.5. Tablet Hardness 35

4.1.6. Wetting time 37

4.1.7. Water Absorption Ratio 38

4.1.8. Disintegration time 39

4.1.9. HPLC Analysis 40

4.1.10. Tablet Dissolution Test 47

4.1.11. FT-IR Spectrum of Different Formulations 48

4.1.12. X-Ray Diffraction of Powder (XRPD) 55

4.1.13. Scanning Electron Microscopy (SEM) 58

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 5. Chapter 5: Discussion 60

5.1. Discussion and Conclusion 63

6. Chapter 6: References 68

LIST OF FIGURES

Figure No. Description Page

Number
1.1 Chemical Structure of Cyclobenzaprine HCl 06

4.1 Impact Durability of different formulation of 36

Cyclobenzaprine Hydrochloride Tablets

4.2 Hardness of different formulations of Cyclobenzaprine 36

Hydrochloride tablets

4.3 Wetting time of different formulations of Cyclobenzaprine 37

hydrochloride tablets

4.4 Water absorption ratio of different formulations of 38

Cyclobenzaprine Hydrochloride tablets

4.5 Disintegration Time of different formulations of 39

Cyclobenzaprine Hydrochloride tablets

4.6 Assay of different formulations of Cyclobenzaprine 40

Hydrochloride tablets by HPLC analysis

4.7 HPLC Spectrograph of Cyclobenzaprine hydrochloride raw 41

material

4.8 HPLC Spectrograph of Cyclobenzaprine hydrochloride 42

tablet Batch No. A1

4.9 HPLC Spectrograph of Cyclobenzaprine hydrochloride 43

tablet Batch No. A2

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4.10 HPLC Spectrograph of Cyclobenzaprine hydrochloride 44

tablet Batch No. A3

4.11 HPLC Spectrograph of Cyclobenzaprine hydrochloride 45

tablet Batch No. A4

4.12 HPLC Spectrograph of Cyclobenzaprine hydrochloride 46

tablet Batch No. A5

4.13 Graphical comparison of active pharmaceutical ingredient 50

with A1 Batch formulation of cyclobenzaprine

hydrochloride tablet

4.14 51
Graphical comparison of active pharmaceutical ingredient

with A2 Batch formulation of Cyclobenzaprine

hydrochloride tablet

4.15 Graphical comparison of active pharmaceutical ingredient 52

with A3 Batch formulation of Cyclobenzaprine

hydrochloride tablet

4.16 Graphical comparison of active pharmaceutical ingredient 53

with A4 Batch formulation of Cyclobenzaprine

hydrochloride tablet

4.17 Graphical comparison of active pharmaceutical ingredient 54

with A5 Batch formulation of cyclobenzaprine

hydrochloride tablet

4.18 FTIR spectrograph results comparative graph for 55

formulations of Cyclobenzaprine Hydrochloride tablets

4.19 XRD diffractograph of Cyclobenzaprine hydrochloride raw 56

material

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4.20 XRD Diffracto-graph of Cyclobenzaprine hydrochloride 56

batch A4

4.21 XRD Diffracto-graph of Cyclobenzaprine hydrochloride 57

batch A5

4.22 Micrograph of Cyclobenzaprine hydrochloride raw 58

material at 5 µm Resolution.

4.23 Micrograph of cyclobenzaprine hydrochloride raw material 59

at 50 µm resolution.

4.24 Micrograph of cyclobenzaprine hydrochloride tablet batch 59

A4 at 5 µm resolution.

4.25 Micrograph of cyclobenzaprine hydrochloride tablet batch 60

A4 at 5 µm resolution.

4.26 Micrograph of cyclobenzaprine hydrochloride tablet batch 60

A5 at 10 µm resolution.

4.27 Micrograph of cyclobenzaprine hydrochloride tablet batch 61

A5 at 20 µm resolution.

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 LIST OF TABLES

TABLE DESCRIPTION PAGE NO.

NO.
3.1 Formulation of five batches of orally dispersible tablet 22

dosage forms

3.2 Unit Formulations of Oral Dispersible Cyclobenzaprine 23

HCl

3.3 Angle of Repose 24

3.4 Compressibility index and flow description 26

3.5 Hausner’s Ratio and Flow Relation 26

4.1 Physical Characteristics of powders of various 34

formulations of tablet of Cyclobenzaprine HCl

4.2 Physical properties of different formulations of 35

Cyclobenzaprine Hydrochloride Tablets

4.3 Wetting time of different formulations of Cyclobenzaprine 37

HCl

4.4 Water absorption ratio of different formulations of 38

Cyclobenzaprine HCl

4.5 Disintegration Time of different formulations of 39

Cyclobenzaprine Hydrochloride tablets

4.6 Percentage drug content of different formulations of 40

Cyclobenzaprine HCl

4.7 Dissolution Test in acidic media performed at different 47

time intervals of Cyclobenzaprine Hydrochloride Tablets

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4.8 Dissolution Test in phosphate buffer media performed at 48

different time intervals of Cyclobenzaprine Hydrochloride

Tablets

4.9 Percentage drug content of different formulations of 49

Cyclobenzaprine HCl in FTIR

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 Abstract

Pharmaceutical technologists have adopted various methods for preparation of

orodispersible tablets however, tablet compression is the most common technique adopted for

preparation of orodispersible tablets. The aim of the present research was to prepare taste

masked oral dispersible tablets by direct compression method. This was followed by

investigation of the effects of super disintegrants (Kyron-T314) and cross carmellose sodium

on the disintegration time, taste masking and percent release of a model drug from Kyron-t314

and cross carmellose sodium based formulations cyclobenzaprine hydrochloride was taken as

model drug for this study. Due to wetting action of sorbitol powder and super disintegrant

Kyron-t314, easy penetration of dissolution media was achieved for rapid release of drug.

Compatibility of formulation was checked by FTIR and XRD studies. The granules and tablets

were evaluated and found to be acceptable according to standard limits. In-vitro release studies

were performed using USP apparatus-II (paddle method) in 900ml of 0.1N HCl (pH 1.2) at

50rpm and 0.1 N phosphate buffer (pH 7.2). Kyron-t314 was found to cause a rapid

disintegration of orodispersible tablets within 28-43 seconds. The highest drug release was

obtained from A-5 (102.85 %). Finally, the overall study indicated a proper balance between

the taste masking and disintegration. The drug release profile of orodispersible tablets in the

presence of a wetting agent showed an acceptable disintegration time with acceptable

percentage of drug release.

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DESIGN AND IN-SITU EVALUATION OF TASTE

MASKED ORODISPERSIBLE TABLETS OF

CYCLOBENZAPRINE HYDROCHLORIDE

By

Muhammad Ayub Naveed

Thesis submitted in partial fulfillment of

The requirements for the degree of

MASTER OF PHILOSOPHY

IN

PHARMACEUTICS

Lahore College of Pharmaceutical Sciences

Affiliated with
College of Pharmacy,
University of Sargodha, Sargodha
2014-2016

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