Effect of preparation methods on tosufloxacin tosylate/ hydroxypropyl-β-cyclodextrin inclusion complex

Abstract The main purpose of this work was to compare the effects of the four preparation methods on the TFLX/HP-β-CD inclusion complex. The effects of different preparation methods on the inclusion complex were investigated by SEM, DSC, PXRD, FT-IR and 1H NMR. All the characterization information indicated that the four preparation methods could cause interaction between TFLX and HP-β-CD, but the inclusion complex prepared by solvent evaporation has more reaction sites. Phase solubility experiments demonstrated that the inclusion reaction was spontaneous. In vitro dissolution experiments showed that the dissolution of the inclusion complex in water was: solvent evaporation method (64.39%) > grinding method (42.37%) > ultrasonic method (40.00%) > freezing method (36.08%), and all higher than pure TFLX and physical mixture. These results suggest that the solvent evaporation is the most suitable method for preparing TFLX/HP-β-CD inclusion complexes.

Simultaneous Determination of 6 Organic Solvents in Tosufloxacin Tosylate by Headspace GC / 中国药房

OBJECTIVE:To establish a method for the residual simultaneous determination of methanol,alcohol,dichlorometh-ane,n-hexane,tetrahydrofuran and benzene in tosufloxacin tosylat. METHODS:Headspace GC was performed on the capillary col-umn with 6%cyanopropylphenyl-94%dimethylpolysiloxane(DB-624)as fixative lipid,temperature programmed,the inlet temper-ature was 180 ℃,detector was flame ionization detector with temperature of 300 ℃,carrier gas was high purity N2 at a flow rate of 1.5 mL/min,split ratio was 10:1,headspace equilibrium temperature was 100℃,equilibrium time was 40 min,headspace sam-ple volume was 10 mL,and the headspace sample volume was 1 mL. RESULTS:The linear range was 178.3-1782.7 μg/mL for methanol (r=0.9991),301.2-3012.1 μg/mL for alcohol(r=0.9997),33.81-338.10 μg/mL for dichloromethane(r=0.9993), 18.02-180.22 μg/mL for n-hexane(r=0.9991),43.26-432.58 μg/mL for tetrahydrofuran(r=0.9991)and 0.1268-1.2681 μg/mL for benzene(r=0.9991);limits of quantification were 0.31,3.00,0.67,0.02,0.005,0.10 μg/mL,limits of detection were 0.15, 1.51,0.22,0.01,0.001,0.05 μg/mL;RSD of precision test was no higher than 3.1%;RSDs of methanol and n-hexane in stabili-ty and reproducibility tests were no higher than 5%;recoveries were 93.72%-102.20%(RSD=3.1%,n=9),90.10%-101.79%(RSD=4.0%,n=9),97.07%-103.11%(RSD=2.0%,n=9),92.38%-103.83%(RSD=3.9%,n=9),95.44%-103.62%(RSD=2.8%,n=9),and 94.00%-104.73%(RSD=4.1%,n=9). CONCLUSIONS:The method is rapid,sensitive,accurate,and suitable for the residual determination of methanol,alcohol,dichloromethane,n-hexane,tetrahydrofuran and benzene in tosufloxacin tosylat.

Clinical Analysis of the 0.3% Tosufloxacin Ophthalmic Solution Effect on Conjunctival Normal Flora

PURPOSE: To report the outcomes of clinical analysis on the negative culture rate of normal ocular surface flora and the anterior chamber penetration after the preoperative prophylactic use of 0.3% tosufloxacin ophthalmic solution. METHODS: From July 2010 to June 2012, 38 eyes of 38 patients who were scheduled to receive intravitreal injection or cataract surgery were examined for bacterial culture positive rate using conjunctival scraping. The patients were treated with 0.3% tosufloxacin eyedrops preoperatively 5 times a day for 2 days before surgery. After the treatment, the bacterial culture negative rate based on conjunctival scraping was assessed to evaluate the drug efficacy. Of the 38 patients, 19 had cataract surgery. The concentration of tosufloxacin at anterior chamber was assessed in the 19 patients. Additionally, any side effects from the drug were monitored during the treatment. RESULTS: Among the 38 eyes, 21 eyes showed a bacterial culture positive rate before treatment. After the drug treatment, the bacterial culture negative rate was 57.1% (12/21). Coagulase-negative staphylococci were most frequently cultured in 15 (39%) of the 38 eyes before treatment and the negative rate of bacterial culture was 86.7% (13/15) after treatment. Average antibiotic residue concentrations in aqueous humor was 0.050 +/- 0.038 microg/mL. No side effects from the drug were reported during the experimental period. CONCLUSIONS: Although the 0.3% tosufloxacin eyedrops were not effective in all bacterial strains and showed relatively low penetration rate into the anterior chamber, they were effective in some gram positive organisms, particularly in coagulase-negative staphylococci of normal ocular surface flora.

Tosufloxacin Tosylate Increased the Liver Enzyme Levels in a Bladder Cancer Patient with Normal Liver Functions: a Case Report

SUMMARY: We report the first hepatic adverse effect of tosufloxacin tosylate in a muscle invasive bladder cancer patient with normal liver functions and with scheduling to undergo a surgical operation for a neobladder. Tosufloxacin tosylate 150 mg was administered to a 57-year-old man who maintained transurethral resection of bladder tumor (TUR-BT) postoperative multiple medications. His labs presented significant increases in alanine amino transferase (ALT) and aspartate amino transferase (AST) levels with 2-week compliance of 150 mg tablet three times a day. After discontinuing tosufloxacin tosylate, the levels slowly decreased and completely returned to normal ranges without any intervention in a few weeks. The Naranjo Causality Algorithm indicates a probable relationship between increased ALT and tosufloxacin. The patient was to have the second surgical operation as scheduled after getting normal range of ATL level. Therefore, tosufloxacin should be avoided in patients at risk for having liver dysfunctions or diseases if the patients have a schedule for any operation. BACKGROUND: Tosufloxacin tosylate has been shown to have favorable benefits as an antibiotic. Tosufloxacin tosylate may be considered to have the adverse effects such as nauseas, vomiting, diarrhea, abdominal pain, stomatitis, tendonitis, tendon rupture, headache, dizziness, drowsiness, insomnia, weakness, agitation including hemolysis in the event of glucose-6-phosphate dehydrogenase deficiency as other fluoroquinolones. More severe adverse reactions of tosufloxacin tosylate over the above common adverse effects of fluoroquinolones were thrombocytopenia and nephritis. It also is not well known that tosufloxacin can cause hepatic problem. Here the study reports the first hepatic reaction from tosufloxacin and might arouse heath care providers' attention to appropriate drug choice for patients.

Toxic Epidermal Necrolysis Associated with Sorafenib and Tosufloxacin in a Patient with Hepatocellular Carcinoma

This is the first case report to describe a 44-year-old woman with a history of advanced hepatocellular carcinoma who developed toxic epidermal necrolysis (TEN) clinically after taking 400 mg sorafenib (Nexavar(R), BAY 43-9006) and tosufloxacin orally once per day. Both sorafenib and tosufloxacin were eventually discontinued, and the TEN resolved with corticosteroids and supportive treatment. Clinical physicians should be aware of this possible complication so that early interventions can be made.