TIMOLOL TRANSPORT FROM MICROEMULSIONS

Microemulsions as ocular drug delivery systems

António Sousa64427 MBioNano

Index

1. Introduction

• 1.1. Structure of Microemulsions.

2. Matherials and Methods• 2.1. The Surfactant• 2.2. The Co-Surfactant• 2.3. Oil and water phases• 2.4. The Drug - Timolol • 2.5. Antigen Microarray Chips• 2.6. Data Analysis

3. Autoemulsification

• 4.1. Partition Coefficient• 4.2. In vivo distribution of timolol.

4. The Study

5. Conclusion and future Challenges

6. References

Currently Alternative

1.Introduction

Eye Drops

■ Very low bioavaiability.

■ Must be inserted several times a day.

■ Difficult absorption trough the corneal

barrier.

Microemulsions

■ Simple and inexpensive industrial

production and sterilization.

■ Thermodinamically stable.

■ Provide the capacity to make soluble lipophilic

drugs.

1.1. Structure of Emulsions

The systems consists of an aqueous phase, a lipophilic phase and a sufactant agent.

Two immiscible liquids, not yet emulsified.

An emulsion of Phase II dispersed in Phase I

The unstable emulsion progressively separates

The surfactant (purple outline) positions itself on the interfaces between Phase II and Phase I, stabilizing the emulsion

Cloudy appearance;

Energy input required to form an emulsion;

Emulsions

1.1. Structure of Microemulsions

The 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 components

2.1. 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 phases

High 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.

They 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.

2. The components

Influence of co-surfactants on the fluidity of the interfacial film (Th.F. Vandamme, 2002).

2.4. The Drug – Timolol

Timolol maleate 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.

2. The components

2.3. Oil and water phases.

The choice of the oily phase is important because it conditions both the existence of the microemulsion and the solubilization of the drug.

3. Autoemulsifi -cation

Due to the spontaneous formation of the microemulsions, they can be prepared in one step by mixing the constituents with reduced roughness.

Drug

Surfactant

Internal Phase

Ion pairing agent

Co-surfactant

Antioxidizing agent

External Phase

Diagram for the preparation of eye drop microemulsion containing timolol base (Th.F. Vandamme, 2002).

4. The Study

4.1. Partition Coefficient

Timolol 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 Study

4.2. 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

■ Microemulsions able to deliver the drug following a zero kinetic order!

■ Higher bioavailability.

■ 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.

6. References Th.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.