UNIVERSITI TEKNOLOGI MARA

IMPROVEMENT OF GRANULES CHARACTERIZATION USING

POLYETHYLENE GLYCOL (PEG) AS A BINDER VIA MELT

GRANULATION IN PRESSURE SWING GRANULATOR FLUIDIZED

BED

SALINDA BINTI AB GHANI

Thesis submitted in fulfillment of the requirements for the degree of

Master of Science

Faculty of Chemical Engineering

August 2016

CONFIRMATION BY PANEL OF EXAMINERS

I certify that a Panel of Examiners has met on 16 February 2016 to conduct the final examination of Salinda Binti Ab Ghani on her Master of Science thesis entitled "Improvement of Granules Characterization Using Poly-Ethylene Glycol (PEG) As A Binder via Melt Granulation in Pressure Swing Granulator Fluidized Bed" in accordance with Universiti Teknologi MARA Act 1976 (Akta 173). The Panel of Examiners recommends that the student be awarded the relevant degree. The Panel of Examiners was as follows:

Prof IR Dr Jailani Salihon Faculty of Chemical Engineering Universiti Teknologi MARA (Chairman)

Prof MADYA Dr Norazah Abd Rahman Dean Faculty of Chemical Engineering Universiti Teknologi MARA (Internal Examiner)

Dr Mohd Shamsul Anuar Senior Lecturer Department of Process and Food Engineering Universiti Putra Malaysia (External Examiner)

DR MOHAMMAD NAWAWI DATO' HAJI SEROJI Dean Institute of Graduate Studies Universiti Teknologi MARA Date :2nd August, 2016

n

AUTHOR'S DECLARATION

I declare that the work in this thesis was carried out in accordance with the regulations

of Universiti Teknologi MARA. It is original and is the results of my own work,

unless otherwise indicated or acknowledged as referenced work. This thesis has not

been submitted to any other academic institution or non-academic institution for any

other degree or qualification.

I, hereby, acknowledge that I have been supplied with the Academic Rules and

Regulations for Post Graduate, University Teknologi MARA, regulating the conduct

of my study and research.

Name of Student

Student I.D No

Programme

Faculty

Thesis Title:

Signature of student

Date

Salinda binti Ab Ghani

2011166391

Master of Science (Chemical Engineering) - EH780

Chemical Engineering

Improvement of Granules Characterization Using Poly-

Ethylene Glycol (PEG) As a Binder via Melt

Granulation in Pressure Swing Granulator Fluidized

Bed

ABSTRACT

Melt granulation of producing core granules was conducted using Pressure Swing Granulation (PSG) technique to produce spherical shape, narrow size distribution of granules, high granule strength and good content uniformity. Core granule of lactose-poly-ethylene glycol (PEG) with mass ratio of 85 wt%:15 wt% was produced in this study. Two-stage core granules was conducted by supplying hot fluidizing air for 120 minutes at 80 °C which was higher than PEG melting point. As a comparison, the core granules from first stage of PSG were heated in an oven at same temperature and duration. Lactose granules were also produced to represent granules without binder and heating treatment. Next, binderless granulation of mefenamic acid particles was conducted to produce spherical shape, narrow size distribution of granules, high granule strength and good content uniformity by using Pressure Swing Granulation (PSG) technique. Also to investigate compaction behavior of granulated mefenamic acid (MA) into tablet and study the characteristic of MA tablet. Two types of granules namely lactose-mefenamic acid and lactose-PEG-mefenamic acid with mass ratio of 30:70 and 25:5:70 were produced in this study respectively. The later type of granules is heated for 80 °C above the PEG melting point. All granules are uniform, spherical and narrow size distribution whereby the granules size is less than 500 |im. The tensile strength of two-stage core granules is higher than settled-bed core granules due to densification effect during fluidization. The tensile strength of the lactose-PEG-MA is higher than tensile strength of lactose-MA due to heating process. The content of lactose in two-stage core granules is similar to the feed mixture before introduced to granulation process. The drug contents in both types of granules were uniform and almost similar to the drug content introduced before granulation which was 70%. Then, mefenamic tablet were formed by using compression of tableting machine. The prepared tablets then were characterized by using dissolution testing, tensile strength, weight variation and also uniformity. As a result, with the different compression forces, the dissolution rate is high for the samples and gives a percent drug release more than 80 % after 60 minutes. Besides, the hardness and strength of tablet is high and sufficient to withstand to the pharmaceutical process. The weight variation of the tablet product is smaller and the uniformity is high showed that the flow property of the MA is increased.

IV

TABLE OF CONTENTS

Page

CONFIRMATION BY PANEL OF EXAMINERS ii

AUTHOR'S DECLARATION iii

ABSTRACT iv

ACKNOWLEDGEMENT v

TABLE OF CONTENTS vi

LIST OF TABLES x

LIST OF FIGURES xi

LIST OF PLATES xiii

LIST OF SYMBOLS xiv

LIST OF ABBREVIATIONS xv

CHAPTER ONE: INTRODUCTION

1.1 Research Background 1

1.2 Problem Statement 2

1.3 Significance Of Research 3

1.4 Objectives 3

1.5 Scope Of Work 4

1.6 Outline Of The Thesis 4

CHAPTER TWO: LITERATURE REVIEW

2.1 Introduction 6

2.2 Granulation 6

2.2.1 Particle Bonding Mechanisms Of The Granulation Process 8

2.3 Pressure Swing Granulation 12

2.4 Melt Granulation 15

2.4.1 Melt Granulation In High Shear Mixer 16

2.4.2 Melt Granulation In Fluidized Bed 19

2.4.3 Comparison Between Melt Granulation In High Shear Mixer 23

And Fluidized Bed

VI