The Preparation And Performance Research Of Montmorillonite Intercalated Betaxolol Solid Lipid Nanoparticles

This article evaluated the advantageous effect of sustained release properties and itsmechanisms of solid lipid nanoparticles, and the model drug was betaxolol hydrochloride.The eye irritation and cornea permeability of nanoparticles were studied too.First of all, the preformulation study has been completed including solubility, apparentwater partition coefficient of betaxolol hydrochloride. The results indicated that BH wasdetected by HPLC-UV at275nm and the method was reasonable which has been validated.Betaxolol hydrochloride was soluble and alkalescence in water. The solubility of modeldrug in many kinds of organic solvents were similiar to water. Simultaneously, the analysismethods of betaxolol hydrochloride in vitro and in corneal has been established to determinthe concentration. The results suggested that the pH and concentration have an importanteffection on corneal permeability. And the results provided some rationale.We made MMT-drug complex based on the old method of our laboratory and studiedthe preparative method of solid lipid nanoparticles. In order to determine the entrapmentefficiency of nanoparticles, dialysis equilibrium method was established. Then some mainfactors were selected which effected the appearance and entrapment efficiency ofnanoparticles including lipid materials, the amount of drug, the amount of phospholipid, thevolume of the external aqueous phase and the concentration of the internal aqueous phase.The optimal method was selected based of the appearance and entrapment efficiency ofnanoparticles by the orthogonal design table. Modified emulsion-solvent evaporationmethod was employed to prepare nanoparticles. At last, the release mechanisms ofMMT-BH-SLN were compared to BH-SLN and made a system evaluation. The result indicated that the release mechanisms is fit for Weibull..The properties of SLN was investigated including particle size, potential, pH, osmoticpressure and so on. Infrared spectroscopy, XRD diffraction, thermal gravimetric wereapplied to analysis the characteristics of nanoparticles. The result showed the averageparticle size of nanoparticles was150nm and the scope is narrow. The pH value andosmotic pressure were under the requirements of ocular drug formulations. The results ofphase analysis have demonstrated the formation of nanoparticles and the drug wasentrapped in nanoparticles. What’s more, The nanoparticle system was stable at4℃refrigerator for a month.The eye irritation was studied by the method of Draize score. The results showed thatthe cornea and conjunctiva were no obvious irritation after a single large dose andlong-term normal dose. So, it is consistent with the requirements of eye irritation. Themicroscopic observation of eye-tissue sections was no lesions which is consistent with theresults of visual observation.In vitro experiments showed corneal permeability of MMT-BH-SLN was better thanBH and Betopics which suggested solid lipid nanoparticles can sustained release.