| Peptide drug-glutathione(GSH)in the treatment of chloasma has a significant effect.In this paper,we will choose the GSH as a model drug and it will be prepared drug-loaded liposome gel.GSH is unstable in air or in the solution and is susceptible to oxidation by external factors such as light,air,humidity,temperature and so on.Studies have shown that GSH aqueous solution is unstable,which can decrease drug content and make partial pesticide effect lose activity.So,it will result in treatment effect is not significant.Therefore,GSH stability is the main problem that needs to be solved in the research and development process.In this paper,the stability of GSH in different conditions of solvent medium under different conditions(temperature,drug concentration,light,antioxidant,pH value,etc.)to improve its stability will be researched.We will use liposome delivery system which enfold the GSH to achieve its stability and extend the length of peptide drug storage time.1.The screening of different solvent media of dissolving GSHThe effects of four solvents(water,glycerol,1,2-propanediol and polyethylene glycol 400)on the content of GSH were investigated by HPLC with the content of GSH as the index.The results showed that GSH in the four solvents was not stable and the organic solvent could not be used alone.After further mixing the four solvents according to different ratio,the content of GSH were controlled by mixing the four solvents,and the 9th,13 th and 14th groups has small influence on the stability of GSH.So,they can be selected as a follow-up further study on the stability of GSH.2.The stability study of glutathione in different solvent systemsWe take the GSH’s content as the index to investigate stability of GSH under the condition of different factors such as pH,temperature,light,antioxidant,drug concentration and so on.The results showed that the drug was significantly accelerated under the alkaline conditions,having impact on the stability of the drug significantly;the drug in the acidic(pH2～7)conditions are stable,but in order to meet the skin pH value of the human body,so the drug environment should be maintained at a weak acidity(pH 5～7)system.With the increase of temperature,the oxidation reaction was accelerated and the stability was significant,but the 13th group had no obvious effect on the GSH’s stability,which should be kept at low temperature.With the increase of light intensity,the oxidation rate of the drug was faster and the stability,which should be kept in dark place.The composite antioxidant group 9 and Group 14 solutions can reduce the oxidation rate;Group 13 solution,a single antioxidant Vc can make the drug to reduce the oxidation rate and reduce the cumbersome process.So the solution should be added antioxidant to improve drug stability;with the drug concentration increases,the oxidation rate is gentle,having no significant impact on the stability,but the drug concentration should not be too low,should control the drug concentration.3.Process and Prescription Optimization of solvent of dissolving GSHThrough the single factor investigation,the main factors affecting the stability of GSH were finally determined,and the solvent prescription and process conditions of GSH were optimized by star point design-response surface method.The final determination of the process conditions and prescriptions are:weigh accurately the amount of glutathione raw material and dissolve it in mixed solution(water:1,2-propylene glycol:polyethylene glycol 400:Glycerol=5:1:1:1),after completely dissolve,adjust the pH to 6.5 and get clarification solution,at room temperature(25℃)or 30℃.4.The preparation and stability investigation of GSH liposomeThe method of preparing GSH liposomes was determined by combining the preparation methods in the known literature with the data in the experiment,and made the prescription process.The stability of GSH liposomes was investigated under different conditions by color,trait,pH,average particle size,PDI,zeta potential,entrapment efficiency and drug loading.The results were compared with those in the known literature.The results showed that the temperature had a significant effect on the stability of GSH liposomes.At 4℃,the indexes of GSH liposomes did not change obviously.At 20 ℃,the indexes of GSH liposomes did not fluctuate significantly,but under the same conditions,GSH stability was superior to GSH liposomes in the known literature.5.The preparation and stability investigation of GSH liposome gelThe preparation of GSH liposome gel was confirmed by comparing the GSH liposome gel preparation method with the data in the experiment and comparing the external phase in the known literature.The preliminary stability of GSH liposome gel was investigated.The results showed that GSH liposomes were stored at room temperature for 3 months,and the content of GSH liposomes was reduced.It should be stored in cold(2～10 ℃)or refrigerator(4～8℃).In addition,the storage stability of GSH liposome gel was compared with that of homemade GSH solution(using group 13 solvent),GSH solution(using solvent group 13)with compound antioxidant and took them as reference substance.The results showed that the stability of GSH liposome gel was significantly improved at room temperature,and the content of GSH was much higher than that in the former.The content of GSH was higher than that in GSH solution and increased by 8.9 times;Similarly,the stability of GSH liposome gel than its aqueous solution with antioxidant also has a certain increase.Storage for 3 months,the percentage of GSH content is 1.2 times than the latter.In summary,the stability of GSH in different solvents was successfully studied on the basis of the GSH’s stability study and preparation of dosage forms in the literature,and prepare nano-drug delivery system of water peptide drug GSH-liposome gel.The stability of GSH in different solvents,the stability of GSH liposomes and the dosage form gels were further studied.The results showed that the stability of GSH and the dosage in the mixed solvent were good.This paper provides theoretical support and technical methods for the study of the stability of water-soluble peptides and the lipid-mediated drug delivery system. |
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