| Lutein is a natural lutein containing two different ionone rings and is a carotenoid without vitamin A activity.It is mainly distributed in the retina in the human body,which has the effects of reducing light damage to the retina and preventing age-related macular degeneration.However,its water solubility and stability are poor,sensitive to light,heat and humidity.The bioavailability of free lutein in human body is only 2% to 9%,which limits the application of lutein in pharmacy.The vesicles formed by the liposome can encapsulate lutein,insulate the oxidation of lutein by external oxygen gas,light,etc.,and promote the dissolution of lutein in water.The traditional dosage forms are mainly ophthalmic ointments and eye drops,but there are problems such as poor patient compliance and low bioavailability.Ophthalmic temperature-sensitive in situ gels are liquids that are fluid at room temperature and form a semi-solid at eye temperature after administration.The advantage is that it can be in contact with the eyes for a long time,prolonging the residence time of the drug in the eye.Based on the study of lutein liposomes,this subject was further developed into an ophthalmic temperature-sensitive gel,which aims to increase the retention time of lutein in the eye and improve bioavailability.Using gelation temperature and viscosity as indicators,the types and reasonable concentrations of poloxamer homologues,antioxidants,bioadhesives and bacteriostatic agents were screened by pre-experiment and single factor.The main influencing factors were selected and the stars were selected.The point design-effect surface method further screens the formulation and optimizes the preparation process.The optimized prescription is:P407 24.25%P188 3.16%PVPK30 0.5%20% lutein liposome 12.5mlbenzalkonium bromide solution 0.01gpH=7 phosphate buffer solution 100mlProcess: weigh the prescribed amount of P407 and P188,put them in a beaker,add appropriate amount of pH7 phosphate buffer solution,stir the glass rod evenly,put it in the refrigerator at 4?,fully swell;then weigh the prescription PVPK30 in a beaker,add an appropriate amount of phosphate buffer solution of pH=7,dissolve completely at 70?,mix well with P407 and P188 solution after cooling,then place in a refrigerator at 4? for 2 h,take out,add 12.5ml of flavin liposome solution,add0.01% benzalkonium bromide solution,stir evenly,add phosphate buffer solution of pH=7 to the prescription amount,stir evenly;prepare the lutein liposome in situ gel The solution was stored in a refrigerator at 12? in the dark.An in vitro assay for the establishment of lutein liposomal in situ gels.Chromatographic conditions: Dikma Diamonsil C18(4.6 mm × 250 mm,5 ?m)column,detection wavelength: 443 nm,mobile phase: 100% methanol,flow rate:0.4 mlˇmin-1,column temperature: 25?,injection volume: 20 ?L.The method has high sensitivity,precision and accuracy,and is suitable for in vitro analysis of lutein liposome gel.The in vitro release of the drug was studied by membrane-free dissolution.The results showed that the dissolution and drug release of lutein liposome gel accorded with zero-order kinetics.Drug release was mainly controlled by dissolution,and in situ gel extended the release of lutein.The initial stability of lutein was examined according to the 2015 edition of the pharmacopoeia guidelines for stability studies.Influential factors test and accelerated test found that lutein decreased significantly at high temperature(40 ?)and room temperature(25?),long-term test results show that the physicochemical properties ofthe formulation at low temperature(10 ?)is relatively stable,so lutein Liposomal ophthalmic gels should be stored at low temperatures and protected from light.The irritancy of lutein liposome gel was evaluated by Draize eye irritation test.Single dose,multiple doses and histopathological sections showed that the preparation had no obvious irritation to rabbit eyes and histocompatibility was observed. |
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