Study On Breviscapine-Loaded Halloysite Nanotubes Complex

Halloysite?HNTs?is a kind of natural nanotube formed from aluminum silicate.In recent years,it has been widely used in slow-release containers,catalyst carriers,organic polymer fillers,hydrogen storage materials,and nanomaterial templates.Due to the special properties such as large specific surface area,good thermal stability,non-toxicity,and low price,halloysite has a high economic value.In recent years,it has been found to be effective as drug carriers to delay the release of drugs gradually,which accordingly catch the pharmacy researchers'wide attention.At present,the study of halloysite as a carrier of drugs and pharmaceutical excipients has become one of the hot areas in pharmacy research at home and abroad.A high efficiency liquid chromatograph for breviscapine was established,and the stability of temperature and pH for breviscapine were investigated.The results showed that breviscapine was stable at temperature below 40?and pH within 6.8-8.0 within12 h.The complex of halloysite loaded breviscapine was prepared by vacuum negative pressure method.Scanning electron microscopy?SEM?,transmission electron microscopy?TEM?,infrared spectroscopy?FT-IR?,differential scanning calorimetry?DSC?,X-ray diffraction?XRD?verified the formation of the loaded complex.The loading rate and in vitro release of halloysite were investigated.The results showed that the drug loading capacity of the complexwas 4.6%.In vitro release experiments confirmed that the complex of halloysite loaded breviscapine have a certain sustained release effect,but the burst release effect is obvious,and the burst release effect needs to be further improved.In order to further optimize the sustained-release effect,the first method is to coat the breviscapine load with chitosan and glutaraldehyde.The results show that the cumulative release rate of the drug after chitosan coating is too low.The second method was LBL coating.The in-vitro release behavior of the tablets coated with breviscapine was examined after coating.The results showed that the release of the drug was 33%in the first 10 min and the cumulative release in 12 h reached 89%,indicating that the preparation slowed the release rate of breviscapine,LBL coating slow release of the load has played a certain effect.In-vitro release profiles of Breviscapine sustained release preparation and reference preparation were investigated,the result showed that the former Higuchi model.The correlation coefficient?f2?between two release curves is lower than 50,which indicate that the two release profile are different,and the sustained release effect comes not only from the LBL coating but from the combined effect of halloysite and the coating.Rats were given intragastric administration of brevispine-halloysite complex and the pristine brevispine.The results showed that the drug-time curve of brevispine-halloysite complex was more gradual than that of the pristine brevispine,the peak concentration(C_max)was lower than the peak concentration obtained by direct oral administration,and the peak time tmax was prolonged,indicating that the brevispine-halloysite complex has a significant sustained release effect on the release of brevispinefor rats.The safety of the cutellarin-halloysite complex was initially evaluated through rats acute toxicity experiment.The result suggested that no mouse was dead even the administrable dose was the maximum,indicating that the brevispine-halloysite complex has high safety.In a word,the complex of halloysite loaded brevispine was prepared in this study.Due to the low cost and extensive source of halloysite,the loading process is simple;the resulting load has good in vivo and external conditions,sustained-controlled release performance and lower toxicity.Therefore,the cutellarin-halloysite complex has the value for further clinical research and development.