Razvoj koprecipitata amorfnog celekoksiba sa stabilizatorima metodom sprej- sušenja
ABSTRACT 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 carrageenean (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 diffraction revealed 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 carrageenean showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenean 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.
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ABSTRACT: Each of four drugs (ketoprofen, indomethacin, naproxen, and progesterone) was milled with Neusilin (amorphous magnesium aluminosilicate) to effect conversion from crystalline to amorphous states, and the physical stability of the resultant drugs was investigated. Ball milling the drugs alone for 48 h resulted in no amorphization. X-ray powder diffractometry (XPD), birefringence, and differential scanning calorimetry (DSC) data indicated amorphization of all the four drugs on ball milling with Neusilin. Fourier transform infrared spectroscopy (FTIR) data showed a reduction in the absorbance of the free and the hydrogen-bonded acid carbonyl peaks accompanied by a corresponding increase in the absorbance of the carboxylate peak, indicating an acid-base reaction between the carboxylic acid-containing drugs and Neusilin on milling. On storage of milled powders (at 40 degrees C and 75% RH for 4 weeks), XPD, birefringence, and DSC data showed the absence of reversion to the crystalline state, and FTIR data revealed continued absence of the carbonyl peaks. Whereas the carboxylic acid-containing drugs convert from their crystalline acid form to amorphous salt form on milling with Neusilin, progesterone seems to interact with Neusilin via hydrogen bonding. The amorphous Neusilin-bound states of all four drugs were physically stable during storage. The water of adsorption seems to mediate the conversion of the crystalline state to an amorphous Neusilin-bound state.Journal of Pharmaceutical Sciences 04/2003; 92(3):536-51. · 3.13 Impact Factor
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ABSTRACT: Carrageenans were analysed in mixture with polymorphic drugs to test their potential for minimising polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. The kappa-carrageenans Gelcarin GP-812 NF and Gelcarin GP-911 NF and the iota-carrageenan Gelcarin GP-379 NF were tested in comparison to the well-known tableting excipients microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as model drug since its well-known recrystallisation behaviour can be mechanically stimulated. Further on, theophylline monohydrate was used. Its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) drug were compressed up to different maximum relative densities. The data obtained during tableting were analysed by three-dimensional (3D) modelling. Afterwards tablets were broken and examined by Fourier transform Raman spectroscopy in order to determine the degree of transformation inside the tablet. For quantitative interpretation, the intensities of representative bands were used. Thermal analysis was used additionally. Using 3D modelling a decrease of plastic deformation can be noticed in the order HPMC>MCC>carrageenans, whereas DCPD represents an exception because of brittle fracture. Best hindrance of polymorphic transformation showed the carrageenans, the hindrance was slightly worse for HPMC. MCC and DCPD could not hinder transformation. A complete protection of the amorphous form could not be achieved. For theophylline monohydrate, the results were similar.European Journal of Pharmaceutics and Biopharmaceutics 07/2003; 56(1):101-10. · 3.83 Impact Factor
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ABSTRACT: A systematic study of the properties of ritonavir and the influence of polyethylene glycol 8000 (PEG) on ritonavir revealed that amorphous ritonavir dispersions in PEG would have an improved dissolution profile and could exhibit long-term stability. Ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, is highly lipophilic [distribution coefficient (log D)= 4.3, 25 degrees C, pH 6.8], poorly water soluble (400 microg/mL in 0.1 N HCl, 1 microg/mL at pH 6.8, 37 degrees C), and exhibits an exceedingly slow dissolution rate (0.03 mg/cm(2)-min in 0.1 N HCl at 37 degrees C). These properties indicated that a solid dispersion containing ritonavir might be useful for overcoming problems associated with slow dissolution. In addition, ritonavir is a good glass former [glass-transition temperature (T(g))/melting point (T(m)) > 0.7]. Amorphous ritonavir has an apparent solubility of 4 mg/mL in 0.1 N HCl at 37 degrees C and shows reasonable stability at 25 degrees C. Amorphous ritonavir, therefore, has properties desirable for preparing a solid dispersion containing this phase. Since PEG, a commonly used polymer, improved the aqueous solubility of crystalline ritonavir, it was expected to have a positive influence on the dissolution rate of ritonavir. Moreover, PEG was found to have negligible plasticizing effect on amorphous ritonavir, which was beneficial for the stability of the dispersion. Finally, solid dispersions of amorphous ritonavir in PEG were prepared, and these dispersions had improved in vitro dissolution rate and were physically stable for > 1.5 years at 25 degrees C when protected from moisture. The performance of this solid dispersion has been attributed to the physicochemical properties of amorphous ritonavir.Journal of Pharmaceutical Sciences 08/2001; 90(8):1015-25. · 3.13 Impact Factor