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  • Development of spray-dried ...
    Dhumal, Ravindra; Shimpi, Shamkant; Paradkar, Anant

    Acta pharmaceutica (Zagreb, Croatia) 57, Issue: 3
    Journal Article

    The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone. Cilj rada bio je pripraviti u što manje proizvodnih stupnjeva amorfni sustav iz kojeg ljekovita tvar neće kristalizirati za vrijeme proizvodnje i skladištenja. Metodom sprej-sušenja pripravljeni su amorfni celekoksib, čvrsta disperzija celekoksiba s polivinil pirolidonom (PVP) i koprecipitat s PVP i karagenanom (CAR) u različitim omjerima. Dobiveni pripravci su zatim komprimirani u tablete iz kojih je praćeno oslobađanje ljekovite tvari. DSC i XRPD analize ukazuju na amorfnu formu celekoksiba, a IR spektroskopija na vodikove veze između celekoksiba i PVP. Oslobađanje celekoksiba iz čvrstih disperzija i koprecipitata bilo je poboljšano u odnosu na celekoksib i amorfni celekoksib. Amorfni celekoksib nije bio stabilan tijekom skladištenja dok su čvrste disperzije i koprecipitati bili stabilni tijekom tri mjeseca. Tablete čvrstih disperzija celekoksiba s PVP i fizičke smjese s PVP i karagenanom bile su otpornije na kristalizaciju nego amorfni celekoksib za vrijeme kompresije, ali ne i tijekom skladištenja. Tablete s koprecipitatom s PVP i karagenanom imale su sličan profil oslobađanja, a u njima se za vrijeme skladištenja nije kristalizirala ljekovita tvar. Ova iznimna stabilnost može se objasniti viskoelastičnošću polimera CAR i vodikovim vezama između celekoksiba i PVP. Kombinacijom dvaju stabilizatora postignut je sinergistički učinak.