Preparation And Evaluation Of Lipid Nano - Preparation With

Dry eye syndromes(DES) is one of the most common ophthalmic disorders, which is also known as xerophthalmia. Signs and symptoms of DES vary with each individual. Common symptoms of DES can include eye dry and itch, red-eye syndrome, foreign body sensation and blurred vision, mucous discharge, photophobia, and allergy to wind and other external irritations. The illness can cause severe vision loss and even blindness. Symptoms can be improved with treatment, but the disease cannot be completely cured. In order to relieve eye discomfort, ordinary aqueous eye drops are usually applied to moisturize and lubricate eyeballs. Tears substitute, which is called artificial tears, can also be used for better application effect. However, as those formulations are rapidly eliminated on ocular surface, their retention time is too short, resulted in low bioavailability, which is their common weakness.This paper designs a lipid nanoparticles preparation. To get a new type of colloidal system, the mixture of solid-liquid lipids and water are emulsified with the help of emulsifier, by means of mechanical work. It not only avoids a lot of defects, such as the blurred vision of eye ointment caused by high content of solid lipid, poor compliance of patients, and tears dilution caused by application of ordinary aqueous eye drops only, but also can achieve an effect of mending the tear film and hydrating ocular surface through film-forming on ocular surface. It relieves the symptoms of dry eye syndrome effectively and effects equal with sold artificial tears, Tear Natural Forte(TNF).The first chapter mainly deals with the irritation of blank lipid nanoscale formulation(BLNF), with the aim of reducing irritation. Firstly, on the basis of previous studies, the matrices with severe irritation were eliminated through single factor test. Then, formulation and process optimization of BLNF was carried out. Using emulsive state, clarity, size, polydispesity index(PDI) as the indicators to make a performance evaluation, optimal formulation was selected. Finally, the effect of reducing irritation was achieved by adding a certain concentration viscosifier, hyaluronic acid(HA). The blink times of BLNF contained 0.2% or 0.3% HA are both under one in 90 seconds in rabbit blinking test. There is no significant difference in irritation between BLNF and TNF. After that, the physicochemical properties of BLNF were investigated. Size was about 30 ~ 40 nm, PDI was about 0.2 ~ 0.3, zeta potential was between-10 m V and-20 m V, p H was about 7.4, and osmotic pressure was about 280 ~ 320 m Osm/kg. All of those properties meet with ophthalmic preparation requirements. In the end, the stability of BLNF was investigated. The preparation is sensitive to temperature. Its zeta potential was significantly decreased after 10 days at 40 °C. Three months stability of the preparation was measured at both 4 °C and 25 °C. The size and PDI basically stayed unchanged, while the zeta potential showed a slow decrease trend. Generally, the preparation has good stability under low temperature conditions.In the second chapter, considering using FK506 as model drug, FK506-LNF is prepared. BLNF has already had the effect of relieving DES, but FK506 is added in order to further achieve the goal of treating DES. On the basis of optimization of the formula in the first chapter, the solubility of FK506 in liquid lipid and emulsifier was used as a means of investigation, size and entrapment efficiency of FK506 were used as evaluation indicators, using orthogonal experiment to get a further optimization. Finally, FK506-LNF was prepared by using yellow vaseline and wool fat as solid lipid, castor oil as liquid lipid, EL35 and tween 80 as emulsifier. The physicochemical properties of FK506-LNF were measured and the morphology of FK506-LNF was characterized. The size was about 40 nm, PDI was about 0.250, zeta potential was about-20 m V, p H was about 7.5, and osmotic pressure was about 300 m Osm/kg. All of these properties meet with ophthalmic preparation requirements. The fluorescent dye Dir was loaded into FK506-LNF to investigate the retention curve of FK506-LNF, and normal saline(NS) was used as blank control. The elimination half-life of FK506-LNF and NS are 0.52±0.05 h, 0.10±0.03 h, respectively, bioavailability of FK506-LNF is 265.0% higher than NS. Finally, the stability of FK506-LNF was also investigated. Unlike BLNF, the drug-loaded preparation is sensitive to light. The zeta potential was significantly decreased and the drug content decreased to 90% of the initial amount after 10 days in light conditions. This indicates that FK506-LNF needs to be storaged at low temperature and away from light.