| Objective:To search the release in vitro of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir and the permeability of Cornea in Vitro is whether better than the Old. To seek the optimal concentration of the honey in new MU-AN ophthalmic gel prescription, draw down the best dosage regimen, provide a new MU-AN ophthalmic gel that can resists the virus and improve the capabilities of corneal wound healing and regeneration and have less side-effect for clinical to treat Herpes Simplex Keratitis(HSK)Method:Take consistenc、uniformity、stretchability、 moldability(Flexibility) as the evaluation index, Use orthogonal design test、Level consistency checkout to optimization matrix、the ratio of additives、technological parameter; To establish a method to determine the content of Ganciclovir in new MU-AN ophthalmic gel, and the methodology study was investigated; Use the Ganciclovir、Acyclovir as the index, taking the second Oar Method (in Ch.P2010), drug release in vitro test was investigated, setting up the dynamical equation of Ganciclovir release in vitro, calculating the rate of the drug release in vitro and the total drug release percentage parameter in vitro and the margin of error, take95%Confidence interval superposition method to compare the different between the rate of drug release and the total amount of drug release of new MU-AN ophthalmic gel and the Old. Use the GCV、ACV as the index, too, take the franz diffusion cell method, cornea permeability test in vitro was investigated, setting up mathematical model, disposed of Corneal permeability parameter by Maths and Stat, compare the different between the rate of drug permeate and the total amount of drug permeate of new MU-AN ophthalmic gel and the Old, compare the different between the rate of drug release and the rate of cornea permeate of new MU-AN ophthalmic gel、the different between the total amount of drug release and the total amount of cornea permeate; investigate the different of the rate of drug release and the total amount of cornea permeate of new MU-AN ophthalmic gel consist of3%、5%、7%honey by cornea permeability test in vitro.Result:The ratio of matrix、additive is that1.Og PEG4000、4.0g PEG400、1.5g Polysorbate-80; The best craft parameter is that mixing GCV with Polysorbate-80、grind with honey、grind with the meltwater combine PEG400with PEG4000. The result of the determination and methodology researching of Ganciclovir by HPLC of new MU-AN ophthalmic gel is that:some index meet the requirements of quantitative analysis, such as standard curve linear range、instrument precision、 repeatability、stability、sample recovery, the blank test showed no interference. The character of drug release of new MU-AN ophthalmic gel is equal to the Old, the rate of drug release is similar. The amount of drug release is the same, Both drugs meet the requirements of clinical medication, the dosage regimen could be designed to three times a day, the interval time is6-8hour, each eye was given0.1g at a time. The character corneal permeability of new MU-AN ophthalmic gel is better than the Old(The rate of corneal permeability is3.452times of the latter,1.832times of the amount of corneal permeability). It is also better than the market0.15%Ganciclovir ophthalmic gel(The rate of corneal permeability is2.029times of the latter). Otherwise, the market0.15%Ganciclovir ophthalmic gel is better than the market3%Acyclovir ophthalmic gel(The amount of corneal permeability is2.028times of the latter).The drug administration is3times a day accroding to the clinical ophthalmic semisolid preparation, each eye was given0.1g at a time, new MU-AN ophthalmic gel、the market0.15%Ganciclovir ophthalmic gel can meet the requirements of clinical demand, Time Administer Drug and interval time is generally scientific、reasonable、feasible, Providing the basis for the pharmacodynamics, toxicology and clinical study in the next step. The rate of drug release in vitro of new MU-AN ophthalmic gel is1.336times of corneal permeability in vitro; the amount of drug release in vitro is2.044times of corneal permeability in vitro. It is belong to Corneal Rate-limiting ophthalmic gel、the character of drug release is better than corneal permeability, hydrogel matrix and butyl stearate has no influence on drug release, drug would be bring treatment effect after the way that it be released quickly then be dissolved in tear. The rate of corneal permeability of the new MU-AN ophthalmic gel consist of5%honey is1.509times of3%. Similarly,7%is1.483times of3%, the result of compare5%with7%showed no statistically significant; Accumulate Permeate Percentage Y8h (%) of8hours of rabbit corneal in vitro, consist of5%honey is equal to7%, both of them is higher than3%. The amount of corneal permeate of the new MU-AN ophthalmic gel consist of5%honey is1.170times than3%; consist of7%honey is1.171times of3%; the result of compare5%with7%showed no statistically significant too; From the economic view, the new MU-AN ophthalmic gel consist of5%honey should be selectedConclusion:the preparation craft of new MU-AN ophthalmic gel is scientific、reasonable、stability and feasible; the determination of Ganciclovir by HPLC of this preparation is meet the requirements of quantitative analysis; The character of drug release of new MU-AN ophthalmic gel is equal to the Old, The character of Corneal permeability is better than the Old;5%honey is the best; It is belong to Corneal Rate-limiting ophthalmic gel, the character of drug release is better than corneal permeability. The release in vitro and the character of corneal permeability of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir is better than the Old, the dosage regimen is that: three times a day, each eye was given0.1g at a time, the interval time is6-8hour, the time administer drug and interval time is generally scientific、reasonable and feasible, providing the basis for the pharmacodynamics, toxicology and clinical study in the next step... |
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