الفهرس 
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Abstract
Nimesulide is a non-steroidal anti-inflammatory drug (NSAID). It is used as an analgesic, antipyretic and anti-inflammatory drug. Nimesulide is very sparingly soluble in water (≈0.01 mg/mL). The poor aqueous solubility and poor wettability of the drug lead to a variation in the bioavailability. In this study we aimed to improve the physicochemical properties of nimesulide by means of a solid dispersion of the drug in different carriers (Inutec® SP1, HPMC-E5, Gelucire® 44/14, Gelucire® 50/13 and skimmed milk). Binary mixtures of different ratios of drug and carrier were prepared by physical mixing and by dispersion using different methods.
All carriers enhanced the wettability, solubility and the dissolution rate of the binary solid dispersions compared to the pure drug, the corresponding physical mixtures and the commercial NS market tablet. The percentage of drug dissolved in 180 minutes increased from 28% in pure drug up to 100% in solid dispersions depending on the carrier, the concentration of carrier and the method of preparation. The dissolution profiles of NS solid dispersions with the various carriers followed the rank order of: Inutec® SP1 > skimmed milk > HPMC-E5 > Gelucire® 44/14 > Gelucire® 50/13. The least square model from the experimental design for the binary system predicted that the optimum dissolution characteristics can be obtained when using Inutec® SP1.
In the continuation of the study, we used this carrier (Inutec® SP1) with β-cyclodextrin (β-CD) in order to prepare ternary systems. The ternary systems prepared by the inclusion complex in solid dispersion (ICSD) technique and by solid dispersion (SD) technique exhibited higher wettability, solubility and dissolution rate when compared to the binary IC, the pure drug, the corresponding physical mixtures and the commercial NS market tablet. FTIR, DSC and XRPD analyses of binary and ternary systems showed that all solid dispersions prepared by kneading, melting and freeze drying methods and some solid dispersions prepared by solvent methods (NS-Gelucires, NS-skimmed milk, NS-β-CD IC and NS- β-CD-Inutec ICSD) exhibited reduction in the crystallinity of the drug. In NS-Inutec and NS-HPMC solid dispersions and in NS-β-CD-Inutec SD prepared by solvent method, the drug recrystallized as a mixture of polymorphic forms of nimesulide.
Almost all solid dispersions remained stable during both accelerated and long term stability studies.
The efficiency was evaluated by anti-inflammatory activity on rats using the Carrageenan-induced rat paw edema model. Nimesulide solid dispersions showed increase in anti-inflammatory activity as compared to nimesulide market tablet. The NS-Inutec formulation (F6) was significantly the most efficient one