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Self-assembled liquid crystalline nanoparticles as an ophthalmic drug delivery system. Part II: optimization of formulation variables using experimental design.

Drug development and industrial pharmacy (2014-02-14)
Djamila Achouri, Michelle Sergent, Alain Tonetto, Philippe Piccerelle, Véronique Andrieu, Virginie Hornebecq
ABSTRACT

In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated.

MATERIALS
Product Number
Brand
Product Description

Supelco
Riboflavin (B2), analytical standard
Sigma-Aldrich
Sodium phosphate, 96%
Riboflavin for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(−)-Riboflavin, meets USP testing specifications
Sigma-Aldrich
(−)-Riboflavin, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%
Sigma-Aldrich
(−)-Riboflavin, from Eremothecium ashbyii, ≥98%
Supelco
Riboflavin, Pharmaceutical Secondary Standard; Certified Reference Material