UNIVERSITI PUTRA MALAYSIA COMPRESSION CHARACTERISTICS OF ANDROGRAPHIS PANICULATA HERBAL PLANT EXTRACT

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UNIVERSITI PUTRA MALAYSIA COMPRESSION CHARACTERISTICS OF ANDROGRAPHIS PANICULATA HERBAL PLANT EXTRACT NORAWANIS ABDUL RAZAK FK 2010 102

COMPRESSION CHARACTERISTICS OF ANDROGRAPHIS PANICULATA HERBAL PLANT EXTRACT NORAWANIS ABDUL RAZAK MASTER OF SCIENCE UNIVERSITI PUTRA MALAYSIA 2010

COMPRESSION CHARACTERISTICS OF ANDROGRAPHIS PANICULATA HERBAL PLANT EXTRACT By NORAWANIS ABDUL RAZAK Thesis Submitted to the School of Graduate Studies, Universiti Putra Malaysia, in Fulfilment of the Requirements for the Degree of Master of Science March 2010

Abstract of thesis presented to Senate of in fulfilment of the requirement for the degree of Master in Science COMPRESSION CHARACTERISTICS OF ANDROGRAPHIS PANICULATA HERBAL PLANT EXTRACT Chairman Faculty By NORAWANIS ABDUL RAZAK March 2010 : Dr. Yus Aniza Binti Yusof, PhD : Engineering This study was conducted to investigate tablet formulation of Andrographis paniculata extract powder by direct compression in a 13mm-diameter-cylindrical unaxial die in two different amounts of feed, 0.5 and 1.0g. The tablets were formed using microcrystalline cellulose and k-carrageenan as binders. The compression pressure was varied between 7.5 to 73.8 MPa. Kawakita and ludde (1970/71) and Heckel (1961) models were selected to validate the experimental data. The objectives were to (i) examine the compressibility of Andrographis paniculata in the presence of binders (ii) validate the data with established models that describes the compression, and (iii) determine their optimum operating conditions. Compression characteristics were evaluated using density-pressure and tensile strength-volume reduction relationships. The tablet characteristics including tensile strength, ejection force, friability and dissolution time, were analyzed on different amounts of ii

Andrographis paniculata and binders. The tensile strength was positively related to the volume reduction, tablet s density and applied pressure during compression. This study showed that microcrystalline cellulose had better binder quality compared to k- carrageenan in direct compression of Andrographis paniculata tablet. The shape, size and quantity of the feed powders greatly affected to the particle arrangement during compression. The optimum condition and formulation for Andrographis paniculata tablet at 0.5g of feed powder was 10 to 30% microcrystalline cellulose at 37.7 to 73.8 MPa pressure. However, at 1.0g of feed powder, the best formulation was 30% microcrystalline cellulose at 52.7 to 73.8 MPa pressure. When k- carrageenan was used as a binder, the best formulation was 10% k-carrageenan at 73.8 MPa pressure. The k-carrageenan can be used in pharmaceutical tablet manufacturing because of its health benefits and much lower price compared to microcrystalline cellulose. This data for tablet processing may contribute to the development of herbal tablet industry in Malaysia. iii

Abstrak thesis yang dikemukakan kepada Senat sebagai memenuhi keperluan untuk ijazah Master Sains SIFAT KEMAMPATAN EKSTRAK TUMBUHAN HERBA ANDROGRAPHIS PANICULATA Pengerusi Fakulti Oleh NORAWANIS ABDUL RAZAK Mac 2010 : Dr. Yus Aniza Binti Yusof : Kejuruteraan Penyelidikan ini bertujuan untuk mengkaji pembentukan dan perumusan serbuk ekstrak Andrographis paniculata melalui kaedah pemampatan terus di dalam acuan silinder berdiameter 13mm. Pil dibentuk dengan penambahan serbuk pengikat selulos mikrokristalin dan k-carrageenan. Tujuan penyelidikan adalah untuk (i) mengkaji kemampatan Andrographis paniculata bersama pengikatnya (ii) mengesahkan data yang diperoleh melalui persamaan yang telah terbukti (iii) menentukan keadaan optima operasi semasa proses pemampatan. Sifat kemampatan dinilai menerusi perkaitan ketumpatan-tekanan dan perkaitan kekuatan keteganganpengurangan isipadu. Sifat pil seperti kekuatan ketegangan, daya penyingkiran, kerapuhan dan masa keterlarutan telah dianalisis mengikut berat jisim Andrographis paniculata serta pengikatnya yang berbeza. Kekuatan ketegangan berkaitan dengan pengurangan isipadu dan ketumpatan pil serta tekanan yang dikenakan semasa iv

proses pemampatan. Hasil penyelidikan ini menunjukkan bahawa selulos mikrokristalin memiliki kualiti yang lebih baik berbanding k-caraagenan semasa proses pemampatan Andrographis paniculata. Rupa bentuk, saiz serbuk dan kuantiti serbuk memberi kesan melalui proses pergerakan partikel semasa proses pemampatan. Keadaan dan perumusan yang optima bagi selulos mikrokristalin adalah pada julat rumusan 10 sehingga 30% dan julat tekanan 37.7 sehingga 73.8 MPa sebagai bahan pengikat untuk pil Andrographis paniculata yang berjisim 0.5g. Walau bagaimana pun, rumusan terbaik untuk 1.0g kuantiti serbuk adalah 30% selulos mikrokristalin pada tekanan 52.7 sehingga 73.8 MPa. Apabila k-carrageenan digunakan sebagai bahan pengikat rumusannya adalah 10% pada tekanan 73.8 MPa sahaja. Pemilihan k-carrageenan sebagai bahan pengikat mungkin boleh digunakan dalam sektor pembuatan pil farmasi berdasarkan komponen semulajadi yang dimilikinya adalah baik untuk kesihatan dan harganya yang murah berbanding dengan selulos mikrokristalin. Data ini adalah untuk pemprosesan pil ubatan dan mungkin boleh member sumbangan dalam pembangunan industri penghasilan pil herba di Malaysia. v

ACKNOWLEDGEMENTS I would like to express special gratitude to Dr. Yus Aniza binti Yusof, my supervisor for her guidance, valuable advices and suggestions. Her patient in guiding me throughout the study is most unforgettable. I would also like to thank all technician and laboratory assistance of Food Engineering Lab (UPM) and Pharmacy Lab (UiTM) for their consistent helps and advices by providing me all the necessary information, materials and equipments for my study. Finally, my earnest appreciation is to my family and friends for their encouragement and demonstration of love. The spirit, the will to win, and the will to excel are the things that endure. These qualities are so much more important than the events that occur. By Vince Lombardi vi

I certified that an examination committee has met on to conduct the final examination of Norawanis Binti Abdul Razak on her Master of Science thesis entitle Compression Characterictics of Andrographis paniculata Herbal Plant Extract in accordance with Universiti Pertanian Malaysia (Higher Degree) Act 1990 and Universiti Pertanian Malaysia (Higher Degree) Regulation 1981. The Committee recommended that candidate be awarded relevant degree. Members of the Examination Committee were as follows: Chairman, PhD Lecturer Faculty of Engineering (Chairman) Examiner 1, PhD Lecturer Faculty of Engineering (Internal Examiner) Examiner 2, PhD Professor Faculty of Food Science (Internal Examiner) External Examiner, PhD Lecturer Faculty of Engineering (Internal Examiner) BUJANG KIM HUAT, PhD Professor and Deputy Dean School of Graduate Studies Date: vii

This thesis was submitted to the Senate of and has been accepted as fulfilment of the requirement for the degree of Master of Science. The members of the Supervisory Committee were as follows: Yus Aniza Yusof, PhD Senior Lecturer Faculty of Engineering (Chairman) Chin Nyuk Ling, PhD Senior Lecturer Faculty of Engineering (Member) Suhaila Mohamad, PhD Professor Faculty of Food Science (Member) HASANAH MOHD. GHAZALI, PhD Professor and Dean School of Graduate Studies Date: 15 July 2010 viii

DECLARATION I declare that the thesis is my original work except for quotations and citations which have been duly acknowledged. I also declare that it has not been previously, and is not concurrently, submitted for any other degree at or at any other institution. NORAWANIS ABDUL RAZAK Date: 22 March 2010 ix

TABLE OF CONTENTS Page ABSTRACT ABSTRAK ACKNOWLEDGEMENTS APPROVAL DECLARATION LIST OF TABLES LIST OF FIGURES LIST OF ABBREVIATIONS CHAPTER 1 INTRODUCTION 1.1 An overview on herbal medicines in Malaysia 1 1.2 Herbal medicine history 3 1.3 Herbal medicine processing technology 4 1.3.1 Extraction of herbs 5 1.3.2 Drying of herbs 6 1.3.3 Consumption of herbs 7 1.4 Objectives 7 1.5 Outline of the thesis 9 ii iv vi vii ix xii xiii xvii 2 LITERATURE REVIEW 2.1 Introduction 10 2.2 Overview on Andrographis paniculata studies 10 2.2.1 Chemical compounds 12 2.2.2 Pharmacological activities 12 2.2.3 Extraction 13 2.2.4 Safety and dosage limitation 14 2.3 Granulation of powder 15 2.3.1 Wet granulation 15 2.3.2 Dry granulation 16 2.4 Herbal medicine tablet 17 2.4.1 Types of tablet 18 2.4.2 Direct compression 19 2.5 Utilization of binder in herbal medicine tablet 21 2.5.1 Types of binder 21 2.5.2 Microcrystalline cellulose 22 2.5.3 Carrageenan 23 2.6 Compression models 24 2.6.1 Kawakita and Ludde (1970/71) 25 2.6.2 Heckel (1961) 26 2.7 Compression behaviours 27 x

2.7.1 Effect of particle size 29 2.7.2 Effect of particle shape 30 2.7.3 Effect of moisture content 30 2.7.4 Effect of powder flowability 31 2.7.5 Effect of binder 32 2.8 Mechanical strength of tablet 33 2.9 Ejection profiles 35 2.10 Statistical method 37 2.11 Summary 37 3 EXPERIMENTAL PROCEDURES 3.1 Introduction 38 3.2 Experimental design 38 3.3 Test powders 43 3.4 Measurement of powder physical properties 45 3.4.1 Particle size and size distribution 45 3.4.2 Particle shape 48 3.4.3 Moisture content 44 3.4.4 Density measurements and flowability of powders 49 3.5 Compaction equipment 53 3.6 Measurement of tablet physical properties 55 3.6.1 Determination of tablet diameter and thickness 55 3.6.2 Tensile Strength 55 3.6.3 Ejection 56 3.6.4 Tablet Friability Measurement 57 3.6.5 Tablet Dissolution 58 3.7 Experimental data analysis 59 4 RESULTS AND DISCUSSION 4.1 Introduction 60 4.2 Powder physical properties 60 4.3 Analysis of compression behaviors 62 4.4 Model validation 74 4.4.1 Kawakita and Ludde (1970/71) model 74 4.4.2 Heckel (1961) model 82 4.5 Ejection 87 4.6 Selection for the best formulations and conditions 91 4.6.1 Improvement of tensile strength 94 4.6.2 Satisfied tensile strength 94 4.6.3 Tablet friability and dissolution 96 4.7 Summary 99 5 CONCLUSIONS 5.1 Conclusions 103 5.2 Recommendations for future work 107 REFERENCES 108 APPENDICES 1 BIODATA OF STUDENT 1 xi