Research Of Niclosamide-loaded Nanosuspension And Film Coating Agent

Niclosamide is a salicyloyl aniline compound. For excellent molluscicidal effect, low toxicity to human and animals, niclosamide is recommended by WHO for the only one molluscicide. However, the low solubility and poor dispersion in water, thus low suspending rate, limit its molluscicidal effect into full play. So how to increase the solubility and suspending rate is the key issue of raising its molluscicidal effect. Nano-drug suspension is a kind of nanoparticle drug delivery system having been evolved in recent years. It can increase the solubility and dissolution velocity of the poorly soluble drugs, enhancing their medicinal effects. It has advantages of simple technological process, high drug loading capacity. This thesis will introduce nano suspension into niclosamide preparation, which is useful for the study of formulations of poorly soluble drugs. Meanwhile, we developed the study of preparation process and quality of niclosamide film coating agent, which creates new ideas for the research of niclosamide topical formulations. The main results are as follows:(1) Niclosamide-loaded nano suspensions were prepared by high-pressure homogenization technology. The influence of type and amount of wetting agents and suspending agents, type of carriers on the suspending performance were investigated. Also the impact of homogenization pressure and cycle number to the particle size was inspected. The method reproducibility had been checked. The results showed that the major factors affecting the drug nanoparticle size were homogenization pressure and cycle number: Along with the increase of homogenization pressure and cycle number, the particle size of nano-drug suspension was showing a degressive trend with good dispersibility. By controlling homogenization pressure and cycle number, niclosamide nano suspension meeting the size requirement could be prepared. Also, the high-pressure homogenization technology was highly reproducible. In addition, the existence of surfactant could, to some extent, inhibit the reunion of nanoparticles, maintaining the stability of the system.(2) We studied the characterization and physical and chemical characters of niclosamide nano suspensions prepared by high-pressure homogenization. TEM showed the spherical or near-spherical particles. The suspending rate of nano suspensions was far higher than that of the wettable powders. Moreover, the suspension stability was higher, the suspending time was significantly longer.(3) To enhance the stability of niclosamide nano suspension, we produced spraying powders of niclosamide nano suspension by spray drying technology. The quality of spraying powders was inspected and image analysis showed cross-linking structure. The dissolution percentage of niclosamide in the spraying powders was far higher than niclosamide original drug, suspending rate higher than niclosamide wettable powders, wettability had been noticeably improved. Moreover, the suspension stability was higher, the suspending time was longer.(4) The pharmacodynamic study of niclosamide nano suspension was developed. Results showed that: under the same condition, the molluscicidal effect of niclosamide nano suspensions was 2 times of the commercial wettable powders. To achieve the same effect of killing snails, the dosage of niclosamide nano suspensions was only half of the commercial wettable powders. Moreover, with a decrease in drug dosage, drug toxicitiy is lower, which will also reduce the environmental pollution. This is of more practical value.(5) The researches of prescription and process of niclosamide film coating agent were developed. Non-drug preparation is colorless, transparent and clear liquid, while the preparation containing drugs was bright yellow, transparent and clear liquid. There was no such incompatibility phenomenon between the drug and film materials as precipitation and discoloration, Niclosamide film coating agent was easy to coat, fast to dry after coating, capable of forming dry films. The formed films had good adhesion, uniformity and some tear-resistant characteristic, not easy to be broken or exfoliated. When it was applied to the skin surface, people felt smooth, no foreign body sensation; and had a good coupling with the skin, could easily be cleared, no pollution to clothing.(6) The quality of niclosamide film coating agent were studied. Preparation had good liquidity and filming characteristic, could be uniformly coated on the skin. The film had good plasticity, could be easily exposed. The method to determine the content was accurate and simple. The preparation had stable quality, no significant skin irritation. Confected in liquid preparation, the matrix had stable quality, no visible solid ingredients. Stored airtightly at room temperature, viscosity changed little with no corruption phenomena such as metamorphism. The film coating agents made of ethyl cellulose, were consistent with the requirements and standards of quality, could be used as a film-forming material in film coating agents of some poorly soluble drugs.