| Nimesulide (Nim) is COX-2-selective non-steroidal anti-inflammatory drug (NSAID) with strong antiinflammatory, analgesic and antipyretic activity. It is widely used for the treatment of rheumatoid arthritis, osteoarthritis, postoperative trauma and other diseases. Nimesulide is practically insoluble in water (0.01mg·mL-1). The very poor aqueous solubility and wettability of these drugs gives rise to difficulties in pharmaceutical formulations for oral or parenteral delivery, which may lead to variable bioavailability.2-hydroxylpropyl-β-cyclodextrin (HP-β-CD), a hydroxyalkyl derivative, with improved water solubility properties and may be slightly more toxicologically benign and its safety over other cyclodextrins for ocular administration has been well documented. To overcome these drawbacks of Nim, increasing the aqueous solubility of Nim is an important goal. Hence, in the present investigation inclusion complexation of Nim with HP-β-CD was tried with the aim to improve their pharmaceutical properties i.e. solubility in water and dissolution properties. HP-β-CD is relatively non-toxic compared with organic solvents and surfactant formulations. It has also been used to reduce ophthalmic drug irritation and to increase chemical stability of drugs in aqueous ophthalmic formulations.The UV and HPLC methods were selected to determinate the content of inclusion complex. The result of methodology studies showed that these methods are simple, accurate and good repeatability. Nim-HP-β-CD was preparation by ultrasonic method and identified by phase solubility study, UV spectroscopy, infrared spectrophotometry, X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The dissolution rates of Nim, physical mixture and inclusion complex were also studied. Inclusion complex lead to a higher solubility and dissolution rate. The inclusion rate of inclusion complex was used as an indicator. The conditions of preparation were investigated with the orthogonal test and analyzed by ANOVA. It was found that the increasing reaction time and the amount of HP-β-CD could enhance the inclusion rate of inclusion complex. And then the optimized conditions were 0.1% HPMC, 5×10-3M NaOH, 15% HP-β-CD and the reaction time 30 min. In this condition, it was helpful to increase solubility and stability by preparing Nim into the Nim-HP-β-CD inclusion complex. The solubility of Nim in inclusion complex was 100 times higher than that of pure Nim. The dissolution of Nim was greatly improved by HP-β-CD. The inclusion rate of inclusion complex reached up to 96.89%.The physicochemical properties of eye drops were studied. Such as appearance, pH, clarity, osmotic pressure, density, viscosity and surface tension. The preliminary stability of the prepared eye drops was investigated and the results showed that the drug content of the eye drops had little change during the accelerated experiment in 3 months. It fit the requirement on eye drops regulated by Chinese Pharmacopoeia.The results of rabbit-eye test indicated that the nimesulide eye drops had no irritation. In addition,the pharmacodynamics of the eye drops were studied.In a word, the preparing technology of Nim-HP-β-CD eye drop was stable. Its characteristics could meet the standard of Chinese Pharmacopoeia. The anti-inflammatory effect of eye drops on rabbit ocular inflammation caused by 10% capsicum tincture is significant. It starts the new route of administration of Nim, and will have amazing market prospect.
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