| Tilmicosin is an animal-dedicated macrolide. It has a strong antibacterial effect, and has a positive effect on the antiviral activity and immunity. However, tilmicosin is limited in clinical application due to the bitterness, alkaline feature, and a stimulative effect on stomach mucosa per os, therefore, it is necessary to develop a gelatin microcapsule which is efficient, safe, sustained-release long-lasting and convenient to delivery.In this experiment, tilmicosin was used as capsule contents and gelatin was used as encapsulating matrial; then, tilmicosin gelatine microcapsules were prepared by single coacervation. In addition, tilmicosin dispersion and solubility test in a gelatin solution, the impact test of wetting agent for microcapsules tilmicosin preparation, the main factors of tilmicosin microcapsules preparation, optimization test, microencapsulated curing conditions orthogonal experiment and microwave drying conditions were applied to studying the formulation technology of tilmicosin gelatine microcapsules. The experiment results as follows:(1) Along with the increase of ultrasonic power, the dispersion time of tilmicosin in the gelatin solution was reduced from 7min 15s to 5min 26s under the condition of 28 KHz frequency and within the range of 40 to 100 watt; moreover, the amount of dissolved drug also increased with the increase of power. The results indicated that 28 KHz frequency and 40 watt were the optimum condition of timicosin dispersed in gelatin solution, now, the dissolution rate was 20%.(2) The loss of timicosin decreased with the increase of pH value in the range from pH 6 to 10, which indicated that the optimum pH range for timicosin is from 9 to 10, and the lowest drug wastage is 4.16±0.48%.(3) The encapsulation rate for timicosin increased and then decreased with the increased of the concentration in the range of the concentration from 0.1% to 0.4% to the wetting agent, and the optimal concentration was 0.3%, at this point, the drug coating rate was 60.61%.(4) Via the single coacervation method to develop the micro-capsule, and the single factor experiment of concentration of gelatin, stirring speed and the encapsulation temperature, The rate of the micro-capsule and the encapsulation rate was higher, and the particle size smaller while gelatin concentration was from 3% to 5%, and the ratio of capsule and material was from 1:3 to 1:5, and stirring speed was 300 r per min to 500 r per min and encystment temperature from 45℃ to 55℃.(5) Via single coacervation method to develop the micro-capsule, B2A2D1C2 was regarded as the optimum technological condition of orthogonal. After 3 times repeated validation, the micro-capsule average coating rate was 79.89±0.25%, and drug loadings was 20.93±0.05%, and the yield of 76.28±0.19%, and the average particle size of 43.12±0.34 microns.(6) Via the orthogonal experiment of curing agent concentration, dosage and curing time three factors three levels, A2B2C2 was deemed to the optimized curing conditions, namely, glutaraldehyde concentration A2, dosage B2 and curing time was C2.(7) Under the condition of microwave P30 (low fire), and P50 (the Med-High fire), and p80 (high fire), the encapsulation rate can reach 80.86±0.25%, and the burst release reach 2.75±0.01%, and the liquidity reach 28.63±0.6°, and the bitterness for timicosinm was reduced from level 5 to level 1, now, the dispersed microcapsules of the high comprehensive score was obtained. |
PDF Full Text Request