Studies On Dry Suspension Of Nitazoxanide And Compound Dry Suspension Of Ivermectin

Nitazoxanide (NTZ) was an interesting parasiticides,fungistatic and molluscicidal agent. As a new broad spectrum antiparasitic agent, NTZ had not been on market in China.To develop the application of NTZ, a series of studies on the dry suspension of NTZ were conducted.The synthetical method of NTZ was studied.To a solution containing a-benzoyl chloride and 2-amino-5-nitro-thiazole in anhydrous tetrahydrofuran,triethylarnine was slowly added while stirring.The obtained precipitate was washed with water,dried and recrystallized from ethanol. Corroborated by TLC.HPLC,IR,UV,¹HNMR and MS,the desired compound had the same results as the standard's. The yields of the desired of the desired compound were between about 35% and 45% and the contend was more than 98%.In order to select an optimized recipe of NTZ for dry suspension , an orthogonal design experiment was carried out by determination of the ratio setting volume, redispersibility and pH value of the suspensions.To establish a HPLC method for determining the content of NTZ in the dry suspension.The DIKMA Diamonsil C₁₈ (4.6×200,5μm) Column was adopted.The mobile phase was 0.2% phosphoric acid water solution:acetonitrile=50: 50( V:V), the detective wavelength was 346nm and the flow rate was 1mL/min.The method was linear within the rage of 17.9¹07.2μg/mL (r =0.9998) .The mean recovery was 103.47%, RSD=0.64%, n=8.It turned out to be a convienient method with good precision. To observe the stability of NTZ dry suspension suspended in water.layed at room temperature,the samples were detected by HPLC at lh,2h,3h,4h,24h,48h,72h,96h,120h and 144h.The suspension was still very stable after 144hrs.Three batches of NTZ suspension were deposited at 40±2℃, RH75%±5% for 3 months, the samples were detected by HPLC at 0,1,2,3 month and the content was still within the setted criterion.Acute toxicity in K.M. mice by oral administration exhibited that NTZ had a low toxicity.and LD₅₀ was4712.38mg/kg.Experiment of NTZ Dry Suspension Expelling Dipylidium caninum was carried out.Six dogs,infected naturally with Dipylidium caninum were given 200mg/kg bw NTZ dry suspension (equal to 100mg/kg bw NTZ)respectively.The results showed that NTZ in a single dose of 100mg/kg bw effectively eliminated Dipylidium caninum.Ivermectin compound dry suspension was prepared and established a HPLC method for determining the content. Acute toxicity in mice by oral administration and experiment of the compound dry suspension expelling digestive tract nematodes in dogs were carried out.