Brimonidine-Soluplus Nanomicelles: Preparation and in-vitro evaluation

Brimonidine is an active pharmaceutical ingredient used to treat glaucoma as a topical eye drop. Ophthalmic topical preparations are associated with low ocular bioavailability due to several physiological and analytical barriers. Many approaches have been investigated to overcome this problem, for example, changing the dosage form by using ocular injections, altering the chemical formula of the medicines as a prodrug, or using different drug carrier systems like nanomaterials. This study aims to prepare nanomicelles as an ophthalmic drug carrier for topical application by using Soluplus® as a polymeric surfactant and enhancing their physical properties by studying different factors. Brimonidine–soluplus nanomicelles were prepared by two methods, thin film hydration and direct dissolution. The physical properties of the prepared nanomicelles were analyzed using two factors, including brimonidine concentration and the ratio of polymer to brimonidine concentration regarding their effect on particle size and entrapment efficiency using Zetasizer and amicon® ultra centrifugal filter units 10 KDa MWCO, respectively. The selected best formula had been characterized by Differential Scanning Calorimetry (DSC), Fourier transform infrared (FTIR), Field Emission Scanning Electron Microscope (FESEM), and in-vitro release pattern compared with free aqueous brimonidine suspension. Results showed that Soluplus® nanomicelle increases the intrinsic solubility of brimonidine compared to free form in water as an aqueous suspension by 2.17 folds for the selected best formula. However, there was a highly significant effect of soluplus® and brimonidine concentrations on the physical appearance and percentage entrapment efficiency of the prepared nanomicelles and non on the polydispersity index. Furthermore, soluplus® concentration had a highly significant effect on the particle size, whereas brimonidine concentration did not. The method of nanomicelle preparation had a highly significant effect on the nanomicelle's physical appearance and percentage entrapment efficiency, in which the thin film was the best. The selected best formula contains 1.98 mg/ml brimonidine with 59.4 mg/ml soluplus had a particle size of (75.75± 1.13nm), polydispersity index of (0.1243±0.02) and percentage entrapment efficiency (53.49±0.58 %) prepared by thin-film hydration method and had a rapid in-vitro release rate (65.52%±0.26) within 15 minutes compared to aqueous brimonidine suspension (23.88%±0.08). DSC, FTIR, and FESEM confirmed the formation of the brimonidine-soluplus-loaded nanomicelles. This study concludes the effectiveness of using a polymeric surfactant to prepare nanomicelles for brimonidine with enhanced physicochemical properties as an ophthalmic drug carrier system.