Research Articles
PLGA nanospheres for the ocular delivery of flurbiprofen: Drug release and interactions

https://doi.org/10.1002/jps.21383Get rights and content

Abstract

Poly(D,L-lactide-co-glycolide) nanospheres incorporating flurbiprofen were prepared by the solvent displacement technique for purposes of assessing (i) drug–polymer physicochemical interactions, (ii) flurbiprofen release from the polymer matrix and (iii) eye permeation of the drug formulated in the colloidal system. The resulting nanospheres were on average 200–300 nm in size and bore a negative charge (ξ-potential around −25 mV). They were shown by atomic force microscopy and transmission electron microscopy to be spherical and regular in shape. Thermal methods, infrared spectroscopy and X-ray diffraction showed that the drug was dispersed inside the particles. These tests evidenced an eutectic mixture meaning more widespread dispersion of the drug in the polymer system. Entrapped flurbiprofen was released in vitro from the polymer system by dissolution and diffusion in high drug loaded nanospheres, whereas those with a lesser load showed only diffusion. The ex vivo corneal permeation study showed that flurbiprofen-loaded nanospheres enhanced drug penetration by about twofold over commercial eye drops containing poly(vinyl alcohol) and by about fourfold over flurbiprofen in pH 7.4 phosphate buffer. The corneal hydration level of each cornea was determined to evaluate potential corneal damage. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5306–5317, 2008

Section snippets

INTRODUCTION

Significant efforts have been made over the last few decades to develop new drug delivery systems that improve the ocular administration of drugs. The use of colloidal drug delivery systems, for example, nanoparticles, is considered nowadays as a strategy that can enhance the ocular bioavailability of topically administered drugs.1 Treatment with these systems increases bioavailability, reduces administration frequency and promotes drug targeting to specific sites. Although a number of polymers

Materials

The poly(lactic-co-glycolic) acid or PLGA polymer chosen was Resomer® RG 756 (Ingelheim, Germany) with a molecular weight of 98,000 Da and a lactide/glycolide molar ratio of 75/25. Poloxamer 188 (Lutrol® F68) was obtained from BASF (Barcelona, Spain). Flurbiprofen and Ocuflur™ were obtained from Sigma (St. Louis, MO) and Allergan (Madrid, Spain), respectively. Double-distilled water was used after filtration in a Millipore® system. All other chemicals and reagents used in the study were of

Nanospheres Characterization

Table 1 describes the physicochemical parameters of the empty and optimized FB-loaded PLGA NEs (F1) obtained in our previous studies13 and the new developed formulations of FB loaded NEs (F2 and F3) prepared at the same concentration as the commercial eye drops (Ocuflur™) to perform the in vitro release and ex vivo permeation studies.

All formulations showed a mean particle size of 200–300 nm which is appropriate for ophthalmic application.21 The particle size distribution was very narrow in all

CONCLUSIONS

This study evaluated the suitability and feasibility of PLGA NEs as an ocular FB delivery system. The size and spherical morphology of the NEs prepared was suitable for ophthalmic administration. A combination of X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry and thermomicroscopy showed the potential of FB-loaded NEs as a drug carrier system where drug dispersion in the polymer system increases FB solubility (FB has a plastic effect on the polymer). FB release

Acknowledgements

The authors wish to thank Hervé Rimbaud at Calytherm and Xavier Alcober in Serveis Cientificotécnics at Barcelona University for their valuable technical assistance. This work was supported by the Spanish Government (CTQ2005-09063-C03-03).

REFERENCES (39)

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