Optimization and Validation of a New Method for the Production of Lipid Nanoparticles for Ophthalmic Application

Rosario Pignatello

doi:10.23937/2378-3664/1410006

Abstract

Within a wider research project aimed at the pre-industrial development of nanotechnology platforms for the treatment of eye diseases, this work exploited the possibility of obtaining solid lipid nanocarriers (SLN) using ingredients and operating conditions that could be compatible with the technological requirements of medical formulations used for ophthalmic therapies and, above all, capable of an easy industrial scale-up. In particular, we tested the possibility of adapting a production method known as Quasi-emulsion Solvent Diffusion (QESD), which already shows a number of operational advantages, such as use of low temperatures and reduced concentrations of surfactants, also to very small production volumes, compatible with expensive and/or poorly available drugs. Cationic SLN (cSLN) were produced using a commercial lipid matrix (Softisan® S100), loaded with a lipophilic probe compound. These cationic carriers could be advantageous in ensuring a prolonged retention onto the negatively charged mucous surface of the cornea. Depending on their composition, cSLN systems with a mean size around 170-250 nm, a good size distribution profile, and a net positive charge (+30/+50 mV) were produced by the QESD technique. Only highly biocompatible, ICH-class 3 solvents, such as ethanol and acetone, were used. Most nanocarriers showed a good physical stability upon storage and could be produced respecting some formulation requirements, such as pH close to neutrality and an osmolarity compatible with the eye surface.

Highlights

The rationale for ophthalmic drug deliveryControlled delivery of bioactive agents to the eye surface or inner structures is a relevant area of drug research and development, though still highly challenging for the pharmaceutical technologists.The eye is protected by anatomical, biochemical and functional fences against the entry of exogenous compounds, comprising most drugs [1]
We have recently proposed a method for producing Lipid nanoparticles (LN) that intrinsically encompasses a number of positive aspects for an ophthalmic or a parenteral formulation
The main advantage of the Quasi-emulsion Solvent Diffusion (QESD) preparation technique is to avoid the use of potentially harmful organic solvents, Table 2: Physico-chemical properties of the solid lipid nanocarriers (SLN) batches

Summary

Introduction

The rationale for ophthalmic drug deliveryControlled delivery of bioactive agents to the eye surface or inner structures is a relevant area of drug research and development, though still highly challenging for the pharmaceutical technologists.The eye is protected by anatomical, biochemical and functional fences against the entry of exogenous compounds, comprising most drugs [1]. We tested the possibility of optimizing the QESD method for producing an ophthalmic nanotechnological formulation, by using a very low surfactant concentration, solvents highly biocompatible with the eye tissues and, above all, working with very small production volumes, an approach that could be beneficial when expensive or scarcely available drugs must be managed.

Results

Conclusion