Microemulsions as ocular drug delivery systemsTimolol transport from microemulsionsAntónio Sousa64427 MBioNano

Index

CurrentlyAlternative1.Introduction

1.1. Structure of EmulsionsTwo immiscible liquids, not yet emulsified.The systems consists of an aqueous phase, a lipophilic phase and a sufactant agent.Cloudy appearance;Energy input required to form an emulsion;An emulsion of Phase II dispersed in Phase IEmulsionsThe unstable emulsion progressively separatesThe surfactant (purple outline) positions itself on the interfaces between Phase II and Phase I, stabilizing the emulsion

1.1. Structure of MicroemulsionsThe systems consists of an aqueous phase, a lipophilic phase and a sufactant agent:Droplet model;Thermodynamically stable. Spontaneous formation.Low percentage of oil or water in the internal phase (≈10%);Transparent, due to the high level of dispersion of the internal phase (100 to 1000Å).MicroemulsionsSometimes its required a co-sufactant.

2. The components2.1. The Surfactant - wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids.Amphiphilic nature.Modification of the physico-chemical properties of the interface.The surfactant concentration is accounts for at least 10% in microemulsions due to the increase of the interface area between the aqueous and oily phasesHigh concentration of surfactants can lead to ocular toxicity.Surfactants used in preparation of microemulsions (Th.F. Vandamme, 2002).

2.2. The cosurfactant – Small molecules, wich generally are alcohols with low molecular weight.2. The componentsThey provide very low interfacial tensions required for the formation of microemulsions and their thermodynamic stability;They can modify the curvature of the interface based on the relative importance of their apolar groups;They act on the fluidity of the interfacial film.Influence of co-surfactants on the fluidity of the interfacial film (Th.F. Vandamme, 2002).

2. The componentsThe choice of the oily phase is important because it conditions both the existence of the microemulsion and the solubilization of the drug.2.3. Oil and water phases.2.4. The Drug – TimololTimololmaleate is a non-selective beta-adrenergic receptor blocker.In its ophtalmic form - brand name Timolol.The fraction of timolol base in the oil phase and also the fraction of the oil phase in the microemulsions are varied to develop systems with different drug loadings.

3. Autoemulsifi -cationDue to the spontaneous formation of the microemulsions, they can be prepared in one step by mixing the constituents with reduced roughness.Internal PhaseIon pairing agentAntioxidizing agentSurfactantDrugExternal PhaseCo-surfactantDiagram for the preparation of eye drop microemulsion containing timolol base (Th.F. Vandamme, 2002).

4. The Study4.1. Partition CoefficientTimolol is associated with a counter-ion in order to improve the lipophilic character of the drug.Partition Coefficient.• Higher bioavaiability;• Delayed release by a reservoir effect.Linear regression between the apparent oil/buffer partition coefficient and the quantity of counter-ions in the internal phase (Th.F. Vandamme, 2002).

4. The Study4.2. In vivo distribution of timolol.The results led to the conclusion that it is preferableto instil the microemulsion dosage form because a low volume of a more concentrated solution can be instilled.Determination of timolol concentrations in aqueous humor according to time (Th.F. Vandamme, 2002).

5. Conclusion and future Challenges■ Delayed effect of the drugs incorporated in microemulsions, which improves their bioavailability.■ Spontaneous formation of microemulsions with reduced size of the droplets on internal phase.■ The choice of the oily phase is also important.■ Microemulsions able to deliver the drug following a zero kinetic order!■ Higher bioavailability.

6. ReferencesTh.F. Vandamme. Microemulsions as ocular drug delivery systems: recent developments and future challenges. Progress in Retinal and Eye Research 21 (2002) 15–34.Araújo J, Gonzalez E, Egea MA, Garcia ML, Souto EB, Nanomedicines for ocular NSAIDs: Safety on drug delivery, Nanomedicine: Nanotechnology (2009), doi:10.1016/j.nano.2009.02.003.Sanjeeb K. Sahoo, Fahima Dilnawaz and S. Krishnakumar. Nanotechnology in ocular drug delivery (2008). Drug Discovery Today. Volume 13, Numbers ¾.