Dorrin Mohtadi Haghighi1, Homa Faghihi2, Majid Darabi1, Maryam Saadat Mirmoeini1, Alireza Vatanara3. 1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Pharmaceutics, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran. faghihi.h@iums.ac.ir. 3. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. vatanara@sina.tums.ac.ir.
Abstract
PURPOSE: Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. METHODS: Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. RESULTS: The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F7 and F8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min. CONCLUSION: SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime.
PURPOSE: Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. METHODS: Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. RESULTS: The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F7 and F8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min. CONCLUSION: SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime.
Authors: Elena Ramirez; Olga Laosa; Pedro Guerra; Blanca Duque; Beatriz Mosquera; Alberto M Borobia; Suhua H Lei; Antonio J Carcas; Jesus Frias Journal: Br J Clin Pharmacol Date: 2010-11 Impact factor: 4.335
Authors: Wilson H Roa; Shirzad Azarmi; M H D Kamal Al-Hallak; Warren H Finlay; Anthony M Magliocco; Raimar Löbenberg Journal: J Control Release Date: 2010-11-06 Impact factor: 9.776