Csaba Bartos1, Rita Ambrus1, Gábor Katona1, Tamás Sovány1, Róbert Gáspár2, Árpád Márki3, Eszter Ducza4, Anita Ivanov4, Ferenc Tömösi5, Tamás Janáky5, Piroska Szabó-Révész1. 1. Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary. 2. Faculty of Medicine, Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary. 3. Faculty of Medicine, Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary. 4. Faculty of Pharmacy, Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary. 5. Interdisciplinary Excellence Centre, Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
Abstract
PURPOSE: The aim of this work was to study the influence of solidification of meloxicam (Mel) containing nanosuspension (nanoMel) on the physical stability and drug bioavailability of the products. The nanoMel sample had poly(vinyl alcohol) (PVA) as a protective polymer, but no surfactant as a further stabilizing agent because the final aim was to produce surfactant-free solid phase products as well. METHODS: The solidified samples produced by fluidization and lyophilization (fluidMel, lyoMel) were examined for particle size, crystallinity, and in vitro release of Mel compared to similar parameters of nanoMel. The products were subjected to an animal experiment using per oral administration to verify their bioavailability. RESULTS: Mel containing (1%) nanoMel sample was produced by wet milling process using an optimized amount of PVA (0.5%) which resulted in 130 nm as mean particle size and a significant reduction in the degree of crystallinity (13.43%) of Mel. The fluidization technique using microcrystalline cellulose (MCC) as carrier resulted in a quick conversion and no significant change in the critical product parameters. The process of lyophilization required a longer operation time, which resulted in the amorphization of the crystalline carrier (trehalose) and the recrystallization of Mel increased its particle size and crystallinity. The fluidMel and lyoMel samples had nearly five-fold higher relative bioavailability than nanoMel application by oral administration. The correlation between in vitro and in vivo studies showed that the fixed Mel nanoparticles on the surface of solid carriers (MCC, trehalose) in both the artificial gastric juice and the stomach of the animals rapidly reached saturation concentration leading to faster dissolution and rapid absorption. CONCLUSION: The solidification of the nanosuspension not only increased the stability of the Mel nanoparticles but also allowed the preparation of surfactant-free compositions with excellent bioavailability which may be an important consideration for certain groups of patients to achieve rapid analgesia.
PURPOSE: The aim of this work was to study the influence of solidification of meloxicam (Mel) containing nanosuspension (nanoMel) on the physical stability and drug bioavailability of the products. The nanoMel sample had poly(vinyl alcohol) (PVA) as a protective polymer, but no surfactant as a further stabilizing agent because the final aim was to produce surfactant-free solid phase products as well. METHODS: The solidified samples produced by fluidization and lyophilization (fluidMel, lyoMel) were examined for particle size, crystallinity, and in vitro release of Mel compared to similar parameters of nanoMel. The products were subjected to an animal experiment using per oral administration to verify their bioavailability. RESULTS: Mel containing (1%) nanoMel sample was produced by wet milling process using an optimized amount of PVA (0.5%) which resulted in 130 nm as mean particle size and a significant reduction in the degree of crystallinity (13.43%) of Mel. The fluidization technique using microcrystalline cellulose (MCC) as carrier resulted in a quick conversion and no significant change in the critical product parameters. The process of lyophilization required a longer operation time, which resulted in the amorphization of the crystalline carrier (trehalose) and the recrystallization of Mel increased its particle size and crystallinity. The fluidMel and lyoMel samples had nearly five-fold higher relative bioavailability than nanoMel application by oral administration. The correlation between in vitro and in vivo studies showed that the fixed Mel nanoparticles on the surface of solid carriers (MCC, trehalose) in both the artificial gastric juice and the stomach of the animals rapidly reached saturation concentration leading to faster dissolution and rapid absorption. CONCLUSION: The solidification of the nanosuspension not only increased the stability of the Mel nanoparticles but also allowed the preparation of surfactant-free compositions with excellent bioavailability which may be an important consideration for certain groups of patients to achieve rapid analgesia.
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