Title Page --- --- --- --- --- --- --- --- --- --- i
Certification --- --- --- --- --- --- --- --- --- --- ii
Dedication --- --- --- --- --- --- --- --- --- --- --- iii
Acknowledgment --- --- --- --- --- --- --- --- --- --- iv
Table of contents --- --- --- --- --- --- --- --- --- --- vi
Abstract --- --- --- --- --- --- --- --- --- --- --- xii
List of tables--- --- --- --- --- --- --- --- --- --- xvii
List of figures--- --- --- --- --- --- --- --- --- ---
xviii
CHAPTER ONE: INTRODUCTION --- --- --- --- --- --- --- 1
1.0 General introduction --- --- --- --- --- --- --- --- 1
1.1 Drug delivery systems--- --- --- --- --- --- --- --- 3
1.2 Various colloidal systems--- --- --- --- --- --- --- --- 4
1.2.1 Liposomes --- --- --- --- --- --- --- --- --- 4
1.2.2 Niosomes --- --- --- --- --- --- --- --- --- --- 5
1.2.3 Solid lipid microparticles (SLMs) --- --- --- --- --- --- 6
1.2.4 Microemulsions --- --- --- --- --- --- --- --- --- 6
1.2.5 Self emulsifying delivery system (SEDD) ------ --- --- --- --- 7
1.2.6 Overview of solid lipid nanoparticles (SLNs) --- --- --- --- --- 8
1.2.6.1 Advantages of SLNs --- --- --- --- --- --- --- --- 9
1.2.6.2 Disadvantages of SLNs --- --- --- --- --- --- --- --- 10
1.2.7 Sustained release formulation --- --- --- --- --- --- --- 11
1.2.7.1 Rationale of formulating sustained release carrier system --- --- --- 12
1.2.7. 2 Advantages of sustained release formulation --- --- --- --- 12
1.3 Materials used in the preparation of SLNs --- --- --- --- --- --- 13
1.3.1 Surfactants --- --- --- --- --- --- --- --- --- --- 13
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1.3.1.1 Classification of surfactants --- --- --- --- --- --- --- 14
1.3.1.2 Cationic surfactants --- --- --- --- --- --- --- --- 15
1.3.1.3 Anionic surfactants --- --- --- --- --- --- --- --- 15
1.3.1.4 Non –ionic surfactants --- --- --- --- --- --- --- --- 16
1.3.1.5 Amphoteric surfactants --- --- --- --- --- --- --- --- 17
1.3.1.6 Hydrophile- lipophile balance value --- --- --- --- --- --- 17
1.3.2 Lipids --- --- --- --- --- --- --- --- --- --- 19
1.3.2.1 Classification of lipids --- --- --- --- --- --- --- --- 20
1.3.2.2 Lipid digestion --- --- --- --- --- --- --- --- --- 23
1.3.3 .1 Polysorbate 80/Tween 80 ---- --- --- --- --- --- --- 28
1.3.3.2 Solutol HS 15 --- --- --- --- --- --- --- --- --- 29
1.3.3.3 Poloxamer 188 --- --- --- --- --- --- --- --- --- 30
1.3.4 Precirol ATO --- --- --- --- --- --- --- --- --- 31
1.3.5. Transcutol HP --- --- --- --- --- --- --- --- --- 32
1.3.6 Tallow fat --- --- --- --- --- --- --- --- --- --- 33
1.4 Techniques in formulation of SLNs --- --- --- --- --- --- --- 35
1.4.1 High pressure homogenization --- --- --- --- --- --- --- 35
1.4.1.1 Hot homogenization --- --- --- --- --- --- --- --- 35
1.4.1.2 Cold homogenization --- --- --- --- --- --- --- --- 36
1.4.2.Solvent emulsification diffusion technique --- --- --- --- --- 36
1.4.3 Microemulsion technique --- --- --- --- --- --- --- --- 37
1.4.4 Solvent evaporation technique --- --- --- --- --- --- --- 37
1.4.5 Spray drying method ------ --- --- --- --- --- --- --- 37
1.4.6 Ultrasonication//high speed homogenication --- --- --- --- --- 38
1.4.7 Double emulsion method --- --- --- --- --- --- --- --- 38
1.4.8 W/O/W Double emulsion method --- --- --- --- --- --- --- 38
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1.5 Overview of drugs used in the formulation --- --- --- --- --- --- 38
1.5.1 Lumefnatrine ------ --- --- --- --- --- --- --- --- 38
1.5.1 1 Chemistry --- --- --- --- --- --- --- --- --- --- 39
1.5.1.2 Mechanism of action --- --- --- --- --- --- --- --- 39
1.5.1.3 Pharmacokinetics --- --- --- --- --- --- --- --- --- 39
1.5.1.4 Toxicity --- --- --- --- --- --- --- --- --- --- 40
1.5.2 Ciprofloxacin --- --- --- --- --- --- --- --- --- 40
1.5.2 1 Chemistry --- --- --- --- --- --- --- --- --- --- 41
1.5.2.2 Mechanism of action --- --- --- --- --- --- --- --- 41
1.5.2.3 Pharmacokinetics --- --- --- --- --- --- --- --- --- 41
1.5.2.4 Toxicity --- --- --- --- --- --- --- --- --- --- 42
1.5.3 Artemether --- --- --- --- --- --- --- --- --- --- 42
1.5.3.1 Chemistry --- --- --- --- --- --- --- --- --- --- 44
1.5.3.2 Pharmacokinetics --- --- --- --- --- --- --- --- --- 44
1.5.3.3 Toxicity --- --- --- --- --- --- --- --- --- --- 45
1.5.3.4 Mechanism of action --- --- --- --- --- --- --- --- 45
1.5.4 Artemether and lumefantrine (AL) combination --- --- --- --- --- 45
1.6 Justification of study --- --- --- --- --- --- --- --- --- 47
1.6.1 Aim of study --- --- --- --- --- --- --- --- --- 48
1.6.3 Objectives --- --- --- --- --- --- --- --- --- --- 49
1.6.4 Literature review --- --- --- --- --- --- --- --- --- 49
CHAPTER TWO: MATERIALS AND METHODS--- --- --- --- --- 55
2.1 Materials --- --- --- --- --- --- --- --- --- --- 55
2.1.1 Animals --- --- --- --- --- --- --- --- --- --- 56
2.2 Methods --- --- --- --- --- --- --- --- --- --- 57
2.2.1 Preliminary studies --- --- --- --- --- --- --- --- --- 57
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2.2.2 Lipid selection by differential scanning calorimetry (DSC) and formulation of
lipid matrix --- --- --- --- --- --- --- --- --- --- 57
2.2.3 Differential scanning calorimetry (DSC) --- --- --- --- --- --- 57
2.2.4 formulation of lipid SLNS --- --- --- --- --- --- --- --- 58
2.2.4.1 General procedure for formulation of SLNs containing Precirol + Transcutol
and Tallow fat + Transcutol --- --- --- --- --- --- --- 58
2.2.4.2 General procedure for formulation of SLNs --- --- --- --- --- 58
2.2.5 Preparation of simulated gastric fluid (SGF) --- --- --- --- --- 60
2.2.6 Preparation of simulated intestine fluid (SIF) --- --- --- --- --- 60
2.2.7 Preparation of 0.1M methanolic HCl --- --- --- --- --- --- 60
2.3 Characterization of SLNs --- --- --- --- --- --- --- --- 60
2 .3.1 Determination of percentage yield --- --- --- --- --- --- --- 60
2.3.2 Particle size and morphology --- --- --- --- --- --- --- 61
2.3.2.1 Particle morphology --- --- --- --- --- --- --- --- 61
2.3.2.2 Particle size and polydispersity index --- --- --- --- --- --- 61
2.3.2.3 Zeta potential analysis --- --- --- --- --- --- --- --- 61
2.4 Degree of crystallinity and polymorphism --- --- --- --- --- --- 62
2.5 Determination of entrapment efficiency of SLNs --- --- --- --- --- 62
2.5.1 Determination of absorption maxima for lumefantrine --- --- --- --- 62
2.5.2 Calibration curve of lumefantrine in 0.1M methanolic HCl --- --- --- 63
2.5.3 Determination of absorbance maxima for ciprofloxacin in 0.1 N HCl (pH 1.2) --- 63
2.5.4 Calibration curve for ciprofloxacin --- --- --- --- --- --- 63
2.6 pH –dependent stability studies of the formulations --- --- --- --- --- 63
2.7 Fourier transform infra red spectroscopy (FT-IR) --- --- --- --- --- 64
2.8 Formulation of liquisolid compacts ( SLNs based tablets of artemether –lumefantrine) 64
2.8.1 Weight uniformity test --- --- --- --- --- --- --- --- 64
2.8.2 Tablet friability test --- --- --- --- --- --- --- --- --- 65
x
2.8.3 Hardness test --- --- --- --- --- --- --- --- --- 65
2.8.4 Disintegration time test --- --- --- --- --- --- --- --- 65
2.8.5 Absolute drug content (assay of artemether) --- --- --- --- --- 65
2.8.5.1 Preparation of standard solution --- --- --- --- --- --- --- 65
2.8.5.2 Determination of absorption maxima for artemether (in distilled water) --- 66
2.8.5.3 Calibration curve of artemether --- --- --- --- --- --- --- 66
2.8.5.4 Assay of artemether in liquisolid compacts /tablets ---- --- --- --- 66
2.8.5.5.5 Dissolution rate test --- --- --- --- --- --- --- --- 67
2.9 In-vitro dissolution studies --- --- --- --- --- --- --- --- 67
2.9.1 In-vitro release of ciprofloxacin loaded SLNs --- --- --- --- --- 67
2.9.2 Drug release study of ciprofloxacin as a function of inhibition zone (IZD ---
68
2.9.3 In-vitro release of lumefantrine and artemether --- --- --- --- --- 68
2.10 In-vivo schizontocidal activity test --- --- --- --- --- --- 69
2.11 Data and statistical analysis --- --- --- --- --- --- --- ---
70
CHAPTER THREE: RESULTS AND DISCUSSION --- ---- --- --- 71
3.1 Characterization of lipid matrices --- --- --- --- --- --- --- 71
3.2 Percentage yield --- --- --- --- --- --- --- --- --- 83
3.3 Differential scanning calorimetry (DSC)for the formulated SLN --- --- 86
3.4 pH- dependent stability studies --- --- --- --- --- --- --- 98
3.5 Morphology and particle size distribution --- --- --- --- --- --- 101
3.6 Encapsulation efficiency --- --- --- --- --- --- --- --- 114
3.7 Tablet properties --- --- --- --- --- --- --- --- --- 116
3.8 Antimicrobial studies of ciprofloxacin --- --- --- --- --- --- 119
3.9 In vitro drug release profile of SLNs loaded ciprofloxacin and SLN lumefantrine
based artemether tablets --- --- --- --- --- --- --- --- 122
xi
3.9.1 In vitro dissolution of lumefantrine --- --- --- --- --- --- --- 122
3.9.2 In vitro dissolution of artemether --- --- --- --- --- --- --- 125
3.9.3 In vitro dissolution of ciprofloxacin --- --- --- --- --- --- 126
3.10 Evaluation of drug release mechanism and kinetics ------ --- --- --- 128
3.11 FT-IR Analysis Results --- --- --- --- --- --- --- --- 131
3.12 In vivo Schizontocidal activity --- --- --- --- --- --- --- 139
CHAPTER FOUR: SUMMARY AND CONCLUSION --- --- --- --- 149
4.1 Summary --- --- --- --- --- --- --- --- --- --- 149
4.2 Conclusion --- --- --- --- --- --- --- --- --- --- 153
4.3 Recommendation (Contribution to Knowledge) --- --- --- --- --- 153
REFERENCES --- --- --- --- --- --- --- --- --- 154
APPENDICES --- --- --- --- --- --- --- --- --- 171
ADAORA, A (2022). Sustained Release Solid Lipid Nanoparticles Formulation of Lumefantrine and Ciprofloxacin. Afribary. Retrieved from https://track.afribary.com/works/sustained-release-solid-lipid-nanoparticles-formulation-of-lumefantrine-and-ciprofloxacin-2
ADAORA, AGATHA "Sustained Release Solid Lipid Nanoparticles Formulation of Lumefantrine and Ciprofloxacin" Afribary. Afribary, 19 Oct. 2022, https://track.afribary.com/works/sustained-release-solid-lipid-nanoparticles-formulation-of-lumefantrine-and-ciprofloxacin-2. Accessed 24 Dec. 2024.
ADAORA, AGATHA . "Sustained Release Solid Lipid Nanoparticles Formulation of Lumefantrine and Ciprofloxacin". Afribary, Afribary, 19 Oct. 2022. Web. 24 Dec. 2024. < https://track.afribary.com/works/sustained-release-solid-lipid-nanoparticles-formulation-of-lumefantrine-and-ciprofloxacin-2 >.
ADAORA, AGATHA . "Sustained Release Solid Lipid Nanoparticles Formulation of Lumefantrine and Ciprofloxacin" Afribary (2022). Accessed December 24, 2024. https://track.afribary.com/works/sustained-release-solid-lipid-nanoparticles-formulation-of-lumefantrine-and-ciprofloxacin-2