| Coccidiosis is a widely distributed protozoan disease, Chicken coccidiosis is a common parasitic disease that has been seriously harmful to poultry industry, with the greatest economic impact on poultry production. The annual cost of anti-coccidiosis medicine was estimated at about $800 million worldwide. The new drug decoquinate is one good anti-coccidiosis medicine,Which has been widely used all over the world and with high efficiency to drug-resistant strains of coccidiosis. Nowdays, The authorized dosage forms being sold of the decoquinate were the solution agent and the premix, less dosage form, Which could not meet the clinical needs, It was urgent to develop water-soluble preparations. For the drug doesn’t dissolve in water, Which was difficult to develop water-soluble preparations, So it seems very essential to prepare the water-soluble dosage of decoquinate. In this research, It was aimed at preparing the solid dispersion of the drug decoquinate, improving its solubility, The result could lay a foundation for the further research of developing water-soluble dosage of decoquinate.In the passage the low co-melt is made up with Decoquinate and different accessory with the method of melt-solvent, and is made into solid dispersion when it is iced. The use of a 34 full factorial design approach helped in optimization of the preparation and formulation of solid dispersion. The optimized formula was the drug and polymer ratio1:8, and the stiring time 30 min, revolving speed 150 rpm. The melt-solvent method was used to prepare solid dispersions. Dissolution test shows that SD technology with a good hydrotropy for Decoquinate, the dissolubility was 152.28μg/mL, the dissolution efficiency at 60 min (%DE60) > 90%, Which met the demand for treatment.The optimized formula was characterized by the differential scanning calorimetery and Fourier transform infrared spectroscopy. The results indicated that after the solid dispersion was made by using the solid dispersing technique, the crystal model of the Decoquinate with the carrier had formed a new substance morphology, and the primary crystal state had changed, equably dispersing in the carrier. The dissoluble curve showed that the dissolution efficiency at 60 min of SD was 90.19% , while its physical compound was only 35.4%, the water-solubility of the Decoquinate was very bad, nearly 0. After the decoquinate was made into physical mixture and SD, the dissolution efficiency of drug was improved obviously.The Quality index such as weight loss on drying, Appearance uniformity and solubility were meet the requirements. The HPLC method has been established for the content determination of decoquinate solid dispersion, a Diamonsil C18(2) column (4.6mm×150mm,5μm) was used with the mobile phase of methanol-water (95:5) solution (to adjust pH of 3.5 by dilute hydrochloric acid ),The UV detection wavelength was 330nm, with a flow rate of 0.6mL/min. The quantification was carried out by the external standard method. Results showed that the limit of detection of the method was 2.5 ng/mL; The calibration curves have good linear over the range of 0.5~10μg/mL with the correlation coefficient of R2 =0.999; The average recovery of decoquinate was 99.61%, with RSD=0.90% (n=9). The average content of SD was 98.73%, with RSD<0.3% Within the batch, with RSD=0.44% between batches; The HPLC method can be used for the content determination of decoquinate, applicable to the product quality control.In this study, the solid dispersion of decoquinate was successfully made, with the content of dispersion 10.97% and the dissolubility 152.28mg/mL in SD.Compared to veterinary drug standard veterinary drug use guide from the People’s Republic of China in 2010, the use usage amount of the fourth new veterinary drug decoquinate solution was 15~30mg/L, the SD of decoquinate could meet the clinical demand. In the finally, the result of this research could provide a scientific proof for the preparation of decoquinate solution, with certain value. |
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