Optimized molecular imprints in gamma-irradiated collagen shields of an antifungal drug: In vitro characterization, in-vivo bioavailability enhancement.

The purpose of this manuscript is to develop sustained release molecularly imprinted voriconazole (VOR) that were loaded into collagen shield (CS) for ocular treatment of fungal keratitis. Various molecularly imprinted polymer (MIP) formulae were prepared by a precipitation polymerization technique. Different monomers and crosslinkers were tested to obtain better binding capacity. Two promising formulae; (F1: VOR: Acrylamide: ethylene glycol dimethacrylate (EGDMA): benzoyl peroxide (BPO) in the molar ratio of 1:5:15:1.6 mM, respectively) and (F3: VOR: Acrylamide: methyl methacrylic acid (MMA): EGDMA: BPO in the molar ratio 1:2.5:2.5:15:1.6 mM, respectively) were selected according to their binding capacities (82.79% ± 0.86, and 94.90% ± 1.25 respectively), and their release profiles over 48 h in simulated tears fluid (STF) (41.64 ± 1.92, and 85.39 ± 1.64 respectively). Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) were carried out. The selected CS (F1 CS and F3 CS) showed sustained release profiles (57.38%± 0.72, and 98.51%±0.49 respectively) over 72 h in STF. Results of trans-corneal permeation and antifungal activity were enhanced for the optimized formula (F3 CS) compared to (F1 CS) and drug solution. Furthermore, in vivo pharmacokinetic studies were conducted showing significant increase in Cmax, delayed Tmax and promoted relative bioavailability. After ocular insertion of F3 CS in male albino rabbits, histopathological studies were attained to assure the safety of the formula. Finally, optimized VOR-MIP-CS could provide promising ocular drug delivery systems (DDS).

New methods for amlodipine and valsartan native spectrofluorimetric determination, with factors optimization study.

Four native fluorescence methods were suggested for simultaneous determination of amlodipine (AML) and valsartan (VAL). These methods were based on excitation of both drugs at λ(ex) 300 nm, in one step, to give maximum emission at λ(em) 378 and 496 nm for AML and VAL, respectively. The first method, single λ(ex) method, was used without any additions. The sensitivity of this method was further increased by the addition of hydroxy propylmethyl cellulose (HPMC) surfactant, ß-cyclodextrin, or ferric oxide magnetite nanoparticles, in the other three methods. Different types of surfactants, and different concentration levels of both ß-cyclodextrin and ferric oxide nanoparticles, were scanned to determine the optimum conditions for enhancing the sensitivity. Some factors affecting the fluorescence intensity of both cited drugs, like the type and volume of the added solvent (to be used as a sensing agent), and pH of measurement were studied and optimized. The proposed methods could be used in determination of AML and VAL in bulk powder, their laboratory prepared mixtures and pharmaceutical formulations. The obtained results were statistically compared to each other and to that of some reported methods. The specificity of the developed methods was investigated, and the methods were validated according to ICH guidelines.