Preparation Of Ketoconazole Solid Lipid Nanoparticles

Objective:Make the ketoconazole into solid lipid nanoparticles formulations to optimize the preparation process,to be able to effectively increase the drug solubility, stability and makes difficult soluble drugs.Against the prepared solid lipid nanoparticles of quality assessment,determination, study of transdermal absorption and skin irritation,and then observe the traetment of tinea mice,for ketone health zun provides reference for the further study of the solid lipid nanoparticles.Method:1.Using microemulsion method to preparation ketoconazole solid lipid nanoparticles.The L9(34)orthogonal was designed by using the encapsulation rate for evaluation index,Through the single factor experiment to inspect the preparation process,and then with dosage of lipid phase,the proportion of emulsifier and co-emulsifier,dosage of the ketoconazole as the study factors.Select the best preparation technology and study its appearance shape、 microscopic morphology and other aspects of the investigation.2.Using high performance liquid chromatography (HPLC) method to determine the content, and its stability were investigated.3. The use of TP-5 transdermal diffusion type intelligent instrument to evaluate the in vitro transdermal sexual.4.Investigate the irritation on normal animal skin and damaged skin by using rabbits about self contrast metbod.5.Made mice tinea model of candida albicans,srudied the effect of ketoconazole solid lipid nanoparticles curative on it.Result:The best preparation process of ketoconazole solid lipid nanoparticle:Glycerin monostearate dosage was 0.5 g,Tween 80 and glycerin dosageratio of 2 g:1.3 g, ketoconazole dosage was 0.04 g, the preparation of ketoconazole solid lipid nanoparticle was clear and transparent,With light blue opalescent,the encapsulation rate was 76.65%. Its microscopic observation were the uniform size of spherical, the average particle size was 61.7 nm,Zeta potential was-23.84mV.The stability test showed,Ketoconazole solid lipid nanoparticle in intense heat, light, and in the long term stability was better under the condition of laboratory.In vitro transdermal permeation test showed that solid lipid nanoparticle formulations penetration effct of ketoconazole.By stimulating experiments showed that the ketoconazole solid lipid nanoparticle had no stimulation to the skin.Antibacterial tests showed:ketoconazole solid lipid nanoparticle has the obvious bacteriostatic effect on the candida albicans.Pharmacodynamics test showed that ketoconazole has good curative effect on mice ringworm of the body, there was no statistically significant difference compared with the positive group (p>0.05), compared with blank group and treatment group matrix do have statistical significance (p<0.05).Conclusion:Ketoconazole solid lipid nanoparticle preparation technology is simple and feasible,Its quality conforms to the requirements,the stability is better,can promote the drug percutaneous osmosis,has no skin irritation,for candida albicans infection of tinea skin diseases with certain effect.