Characterization of Microemulsions using Small Angle Scattering Techniques Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Mathematisch-Naturwissenschaftlich-Technischen Fakultät (mathematisch-naturwissenschaftlicher Bereich) der Martin-Luther-Universität Halle-Wittenberg von Herrn Anuj Shukla geb. am 10. März 1973 in Sitapur (Indien) Gutachter: 1. Prof. Dr. Heinrich Graener 2. Prof. Dr. Reinhard Neubert 3. Dr. habil. Wolf-Dieter Hergeth Halle (Saale), den 12.05.2003 urn:nbn:de:gbv:3-000005108 [http://nbn-resolving.de/urn/resolver.pl?urn=nbn%3ade%3agbv%3a3-000005108]
ii CONTENTS Contents 1. Introduction 1 1.1. What is a microemulsion (ME)? 3 1.2. What does a ME droplet look like? 4 1.3. What is dynamic behavior of ME droplet? 5 1.4. Design of MEs 5 1.5. Applications of MEs 5 2. Small Angle Scattering Techniques 6 2.1. Comparison of Scattering Techniques and 6 the Length Scales which they Probe 2.2. Light Scattering 9 2.3. Small Angle Neutron Scattering (SANS) 11 3. Theoretical Background 12 3.1. Static Light Scattering (SLS) from Interacting ME Droplets 12 3.2. Dynamic Light Scattering (DLS) 17 3.2.1. Monodisperse, Non-Interacting ME Droplets 18 3.2.2. Polydisperse, Interacting ME Droplets 19 3.3. Volume Fraction Dependence of Diffusion Coefficient 23 3.4. SANS from Interacting ME Droplets 25 3.5. The Form Factor 27 3.6. The Structure Factor & Pair Distribution Function 29
CONTENTS iii 3.7. Interdroplet Interaction 31 4. Data Acquisition and Treatment 33 4.1. Data Acquisition: Static and Dynamic Light Scattering 33 4.2. Data Treatment: SLS 35 4.3. Data Treatment: DLS 36 4.4. Data Acquisition and Treatment: SANS 41 5. Results And Discussion 46 5.1. Water AOT n- Alkanes MEs 46 5.1.1. Layered Sphere Model 47 5.1.2. Droplet Size and Polydispersity 51 5.1.2.1. Refractive Index Increment 52 5.1.2.2. DLS Results 53 5.1.2.3. SLS Results 55 5.1.3. Interdroplet Interactions and Droplet size 58 5.1.3.1. SANS and CONTIN Results 58 5.1.3.2. SLS Results 59 5.1.3.3. DLS Results 61 5.1.4. Shape Fluctuations of ME 70 Droplets with Increasing Temperature 5.2. Characterization of Pharmaceutical MEs 73 5.2.1. Interdroplet Interaction and Droplet Size 73 of O/W - MEs of Pharmaceutical Interest 5.2.1.1. DLS Results 74
iv CONTENTS 5.2.1.2. Effect of Proposed Interdroplet Interaction 76 on the Stability of O/W - MEs 5.2.2. Behavior of Each Constituent Solubilized 79 in MEs of Pharmaceutical Interest 5.2.2.1. O/W MEs of Pharmaceutical Interest 80 5.2.2.1.1. MEs with Different Ratios of Water/PG 81 5.2.2.1.2. MEs with Different Amounts of Oil 81 5.2.2.1.3. Effect of Drug Incorporation 82 5.2.2.1.4. MEs with Different Kinds of Oils 83 5.2.2.1.4.1. DLS Results 83 5.2.2.1.4.2. SANS Results 84 5.2.2.1.5. Effect of Temperature on ME Droplet 87 5.2.2.2. W/O MEs of Pharmaceutical Interest 88 5.2.2.2.1. Different Ratios of Span 20/ Tween 80 89 5.2.2.2.2. MEs with Different Ratios of Water/DMSO 91 5.2.2.2.3. MEs with Different amounts of Surfactant 91 5.2.2.2.4. MEs with Different Kinds of Oils 92 5.2.2.2.5. Effect of Temperature on ME Droplets 93 5.3. Characterization of MEs having Local Anaesthetics 94 as Dispersed Phase 5.3.1. Interdroplet Interaction 95 5.3.2. Different Amount of colloidal Phase 96 5.3.3. Effect of ph 96 6. Summary and Conclusions / Zusammenfassung und 97 Schlussfolgerungen 6.1. Model ternary water/aot/n-alkanes MEs 97
CONTENTS v 6.2. MEs of pharmaceutical interest 99 Suggestions for Future Studies I Appendix A II Appendix B VII Appendix C IX Appendix D XII List of References XVI
vi CONTENTS List of Abbreviations AOT AOT-MEs DLS DMSO EMLA EO Eutanol HLB HNC HS IPM IPP ME NMR OA O/W PO Poloxamer 331 PG PY SANS SAS SLD SLS Span 20 Tagat O2 Tween 80 W/O Sodium bis(2-ethylhexyl) sulfosuccinate (Aerosol - OT) Water/AOT/n-alkanes Systems Dynamic Light Scattering Dimethyl sulfoxide Eutectic Mixture of Local Anaesthetics Ethylene Oxide 2-Octyl-1-dodecanol Hydrophilic-Lipophilic-Balance Hypernetted-Chain Hard Sphere Isopropyl myristate Isopropyl palmitate Microemulsion Nuclear Magnetic Resonance Oleic acid Oil-in-Water Propylene Oxide Polyoxyethylene Polyoxypropylene Block co-polymer Propylene Glycol Percus-Yevick Small Angle Neutron Scattering Small Angle Scattering Scattering Length Density Static Light Scattering Sorbitan monolaurate Polyoxyethylene glycerol monooleate Polyoxyethylene sorbitan mono-oleate Water-in- Oil