Development of Acacia Gum (Acacia Seyal) Cross-links as Matrix in Sustained-Release Salbutamol Sulphate Tablet formulations

Development of Acacia Gum (Acacia Seyal) Cross-links as Matrix in Sustained-Release Salbutamol Sulphate Tablet formulations.

ABSTRACT

This study evaluated the potential of cross-linked Acacia seyal gum as a matrix in sustained-release salbutamol sulphate tablet formulations prepared by direct compression method. Cross-linking which involves re-enforcing bonds with chemical bridges between molecules or polymer chains is expected to reduce the solubility of hydrophilic polymers, making them more reliable as sustained-release matrix formers.

The crude Acacia seyal gum was purified and labeled as ―EG‖, then cross-linked with freshly prepared 1.0 M calcium chloride solution to obtain ―CG‖. The cross-linking was confirmed by the percentage yield, differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectrophotometry.

The colour, texture, taste and odour were used to describe the organoleptic characters of the polymers, while the determination of the moisture loss on drying, solubility, viscosity, swelling ratio, swelling rate, hydration capacity, pH, moisture sorption profile, particle size distribution, bulk density, tapped density, true density, flow rate, angle of repose, compressibility index and Hausner‘s ratio was used to characterize the physicochemical and flow properties of the polymers.

Directly compressed tablets were formulated, with a constant quantity of salbutamol sulphate (8 mg), while the matrix material varied between 30, 40 and 50 per cent (%), resulting in formulations T1, T2 and T3 containing EG; T4, T5 and T6 containing CG and; T7, T8 and T9containinghydroxypropyl methylcellulose (HPMC) respectively.

TABLE OF CONTENTS

Cover Page – – – – – – – – ————————- – i

Fly leaf – – – – – – – – – —————————– ii

Title Page – – – – – – – – ————————– – iii

Declaration – – – – – – – – ———————— – iv

Certification – – – – – – – – – ———————– v

Dedication – – – – – – – – – ———————— vi

Acknowledgment – – – – – —————– – – – vii

Abstract – – – – – – – – – – ..———————-.viii

Table of Contents – – – – – – —————- – – x

List of Figures – – – – – – – – —————— – xvi

List of Tables – – – – – – – – ——————- – xvii

List of Plates – – – – – – – – – – ——————xviii

List of Appendices – – – – – – – – ————– xix

Abbreviations – – – – – – – – – – —————–xxi

CHAPTER ONE

1.0 GENERAL INTRODUCTION 

1.1 Preamble – – – – – – – – —————————————- 1

1.2.1 Diluents – – – – – – – —————————————- – 2

1.2.2 Binders – – – – – – – —————————————– – 3

1.2.3 Disintegrants – – – – – ———————————— – – 4

1.2.4 Lubricants – – – – ————————————- – – – – 5

1.2.5 Coating agents – – – ——————————– – – – – – 5

1.2.6 Glidants – – – – – – – —————————————- – 6

1.2.7 Antiadherents – – – ——————————— – – – – – 6

1.2.8 Flavours – – – – – – ————————————— – – 6

1.2.9 Colours – – – – – – – —————————————– – 7

1.2.10 Preservatives – – – – – – – ——————————— – 7

1.3 Modified Release Delivery Systems- – – ————— – – – 7

1.4 Polymers used as matrix formers in sustained release delivery studies – – 9

1.4.1 Acacia gum – – – – – ———————————– – – – 11

1.5 Suitability of Drug for Formulation as Sustained-Release Dosage Form- – 14

1.5.1 Salbutamol – – – – – – – – ———————————– 14

1.6 Statement of the Research Problem – ———— – – – – 15

1.7 Justification – – – – – – ———————————- – – 16

1.8 Aim – – – – – – – – – —————————————— 17

1.9 Specific Objectives – – – – —————————- – – – 17

1.10 Hypothesis – – – – – – ——————————— – – 18

CHAPTER TWO

2.0 LITERATURE REVIEW – – – – – – ———————— 19

2.1 Cross-linking – – – – – ———————————- – – – 19

2.2 Significance of Cross-linking Excipients – – – – ——- – 20

2.2.1 Gums and mucilages – – – – – – – ———————— 20

2.2.2 Cellulose – – – – – – – – – ———————————–34

2.2.3 Hemicellulose – – – – – – – —————————— – 35

2.2.4 Chitosan – – – – – – – – ———————————– – 36

2.2.5 Starch – – – – – – – – – ————————————- 38

CHAPTER THREE

3.0 MATERIALS AND METHODS – – – – – – —————- 41

3.1 Materials – – – – – – – – – ————————————- 41

3.2 Methods – – – – – – – – ————————— ————42

3.2.1 Sample Collection and Identification – ————- — 42

3.2.2 Extraction/Purification – – – – – – – ———————- 42

3.2.3 Crosslinking of the purified Acacia seyal gum (EG) using calcium chloride – 43

3.2.4 Differential Scanning Calorimetry (DSC) – – – – ———- 44

3.2.5 Fourier Transform Infra Red (FT-IR) studies – – – —- – 44

3.2.6 Organoleptic characterization – – – – – – ——————– 44

3.2.7 Physicochemical characterization – – – – – —————— 45

3.2.8 Preparation of salbutamol sulphate sustained-release tablet formulations by direct compression method – – 50

3.3 Evaluation of Tablets – – – – – —————————– – – 52

3.3.1 Weight variation – – – – – – ——————————– – 52

3.3.2 Diameter – – – – – – – ————————————– – 52

3.3.3 Thickness – – – – – – – – ————————————– 52

3.3.4 Friability – – – – – – ————————————— – – 52

3.3.5 Crushing strength – – – – —————————— – – – 53

3.3.6 Tensile strength – – – – ——————————– – – – 53

3.3.7 Disintegration test – – – —————————- – – — – 53

3.3.8 Uniformity of drug content – – – – – —————— —- 54

3.3.9 In-vitro drug release studies – – – – – ——————– – 54

3.3.10 Release kinetics – – – – – ————————— – —– 55

3.3.11 Statistical analysis – – – ———————– – ——- – – 55

CHAPTER FOUR

4.0 RESULTS – – – – – – —————————— – ———- – 56

4.1 Sample collection and identification – – – – —————- – 56

4.2 Extraction and purification yield – – – – – – —————— 56

4.3 Cross-link yield – – – – – – – – —————————- ——-59

4.4 Thermal analysis using differential scanning calorimetry (DSC)- – – 59

4.5 Fourier transform infra-red (FT-IR) studies – – —- ————- 62

4.6 Organoleptic and some physicochemical characterization – – – 65

4.7 Moisture sorption profile – – – – ———————— – ——- – 67

4.8 Particle size distribution – – – – —————————- —- – – 67

4.9Flow properties – – – – – – —————————————- – – 67

4.10 Tablet properties – – – – ——————————- – ——– – 71

4.11 Dissolution studies – – – – —————————- – ——– — 74

4.12 Mathematical models of formulated matrixtablets – – – ——- 77

4.13 Statistical analysis – – – – – – ————————————- – 79

CHAPTER FIVE

5.0 DISCUSSION – – – – – – – —————————————- – 80

CHAPTER SIX

6.0 SUMMARY, CONCLUSION AND RECOMMENDATIONS – -96

6.1 Summary – – – – – – – ———————————————- – 96

6.2 Conclusion – – – – – – – ——————————————– – 99

6.3 Test of Hypothesis – – – – – – ———————————— – 100

6.4 Recommendations – – – – – – – ———————————- – 100

REFERENCES – – – – – ——————————————- – – – 101

INTRODUCTION

Over the years, man has always relied on drugs and medicines to treat, ameliorate, diagnose or prevent diseases and to maintain good health. Tablets are the unit solid dosage forms meant for oral use and are manufactured by using tablet compression machines, by compressing the active pharmaceutical ingredient with other recipients (could be inert or not but majorly to help in giving the formulation some desired characteristics that enable its handling or renders some kind of function)(Nagashree, 2015).

An excipient is a natural or synthetic substance formulated alongside the active ingredient of the medication, including for the purpose of bulking-up formulations that contain potent active ingredients (thus often referred to as ―bulking agents‖, ―fillers‖ or ―diluents‖) or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption or solubility (Narang et al., 2017).

Research and development laboratories are presently finding it difficult to come forth with new drug molecules and even some of the ones existing already are having difficulties in achieving their full profile. There is therefore a need for change in operation to a more optimized way of making drugs more effective by slight modification in their delivery process and one of the ways by which this can be achieved is to sustain the release of the drug.

REFERENCES

Abdulsamad, A., Oyi, A. R., Isah, A. B., & Odidi, I. (2012). Characterisation and studies on binding properties of cashew gum and its mixtures with microcrystalline cellulose in venlafaxine HCl tablet formulations. Nigerian Journal of Pharmaceutical Sciences, 11(2), 9-20.
Abdulsamad, A., Oyi, A. R., Isah, A. B., & Odidi, I. (2014). Cashew gum crosslinked with epichlorohydrin to enhance venlafaxine hydrochloride release from tablets formulated with HPMC as binder. Nigerian Journal of Pharmaceutical Sciences, 13(1), 43-53.
Abdulsamad, A., Oyi, A. R., Isah, A. B., & Odidi, I. (2015). Derivatisation of cashew gum via cross-linking with citric acid: Characterisation and preliminary evaluation of tableting properties. British Journal of Pharmaceutical Research, 6(1), 22-34.
Afrasim, M., Mahesh, M. R., Jagadeeswara, D. R., &Shivakumar H. G. (2012). Formulation of sustained-release matrix tablets using cross-linked karaya gum. Tropical Journal of Pharmaceutical Research, 11(2), 185-192.

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