side effects, and a high therapeutic index.1 N is a relatively weak inhibitor of prostaglandin synthesis in vitro and appears to exert its effect through a variety of mechanisms including free radical scavenging, effects on histamine release, the neutrophil myeloperoxidase pathway, bradykinin activity, tumor necrosis factor-a release, cartilage degradation, metalloprotease synthesis, phosphodiesterase type IV inhibition, platelet aggregation, and synthesis of platelet activating factor. It also exhibits a significant selectivity toward cyclooxygenase-2 (COX-2) versus COX-1 inhibition, which may explain the lower incidence of gastric side effects. However, recent findings reported that N has a higher risk of hepatic toxicity when compared to other marketed NSAIDs.2,3 Like many nonsteroidal anti-inflammatory drugs, N is very sparingly soluble in water (≈ 0.01 mg/mL). 4 The poor aqueous solubility and wettability of N gives rise to difficulties in pharmaceutical formulations for oral or parenteral delivery, which may lead to variable bioavailability. To overcome these drawbacks, increasing the aqueous solubility of N is an important goal. Hence, in this investigation, inclusion complexation of N was tried with α-, β-, and γ-cyclodextrins (CDs) with the aim to improve its pharmaceutical properties (ie, aqueous solubility and dissolution properties).
ABSTRACTThe objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution and solid state and to improve the dissolution properties of nimesulide (N) via complexation with α-, β, and γ-cyclodextrins (CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry, and 1 H nuclear magnetic resonance ( 1 H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder xray diffractometry (X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1 H-NMR studies in solution revealed 1:1 M complexation of N with all CDs. A true inclusion of N with β-CD at 1:2 M in solid state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when compared to pure N.
