Study On Sodium Cromoglicate Gel For Ophthalmic Use

As one of the important fields of controlled release, ophthalmic drug delivery has received extensive interests all the time. The sensitivity and protection mechanisms of eye promote more effective drug delivery systems with higher safty to be researched and developed, however, the applications of various pharmaceutical methods are limited simultaneously, which presents great chanlleges in designing ophthalmic dosage forms. Sodium Cromoglicate was taken as the model drug, and two kinds of pH-sensitive gel and Thermosensitive gel were prepared by hydrophilic high- molecualr materials in the thesis.The first job was to found the UV method that can be used to determine the physicochemical properties of sodium cromoglicate, and then the oil/water partition coefficient of Sodium Cromoglicate was determined.Carbopol934p,Carbopol940p and HPMC(K4M) were taken as the basic matrix of pH-sensitive Sodium Cromoglicate gel for ophthalmic use. It was found that the solution got very ropy when more than 0.5% of carbopol 934p or carbopol 940p was used separately, so that it was unable to determine the viscosity of solution accurately. Therefore, lower than 0.5% of carbopol934p or carbopol940p was taken as gel matrix preliminarily.The viscosity as only judgement criteria, the best formula was screened by uniform design. The obtained best formula contained 2g Sodium Cromoglicate, 0.3g Carbopol 940p, 0.45g HPMC K4M, 0.01g ethylhydroxybenzoate. The viscosity of this formula was 22mPas that complied with the requirement for ophthalmic application. Ophthalmic pH-sensitive Sodium Cromoglicate gel was prepared according to the formula above mentioned, and its content and quanlity were examined. Its content was determined by UV method of the pharmacopoeia, this method was applied for in vitro quality control. The content of the three batches of samples that were prepared fore-and-after determination was equal and stable. Its properties, pH, stability and centrifugal experiment met the requirement. Both of single and repetitious administration wouldn't be amyctic for rabbit eyes.The differences of drug liberation amount in unit time and cumulative drug liberation amounts in definited time between the pH-sensitive Sodium Cromoglicate gel for ophthalmic use and those commerical Sodium Cromoglicate gutta were compared by the excised permeability experiment with rabbit corneas. The experimental results showed that the drug liberation rate of those commerical Sodium Cromoglicate gutta was faster than pH-sensitive Sodium Cromoglicate gel, but their duration was shorter.The Poloxamer solution was prepared by the air-cooling method. It was found that phase-transition temperature decreased with increasing concentration of Poloxamer407 solution by reseaching the relationship with phase-transition temperature and concentration. Furthermore, it was also found that phase-transition temperature of Poloxamer407 solution could be enhanced by Poloxamer188 obviously by studying the effect of Poloxamer 188 on phase-transition temperature of Poloxamer407 solution. It can be seen that NaCl made phase-transition temperature of Poloxamer407 solution declined 2℃averagely by researching the effect of NaCl on phase-transition temperature of Poloxamer407 solution. The effect of manual simulation tears on phase-transition temperature of Poloxamer407 solution was also examined because gutta needs combination with tear as it entering into human beings'eyes(V:V=40:7). It can be seen that phase-transition temperature of Poloxamer407 solution diluted by tears was enhaced evidengtly. The phase-transition temperature of Poloxamer407 solution as primary evaluation criterion, the obtained best formula of Thermosensitive Sodium Cromoglicate gel for ophthalmic use was: 20% of Poloxamer407, 11% of Poloxamer188, 2% of Sodium Cromoglicate, 0.01% of ethylphydroxybenzoate per 100g Thermosensitive Sodium Cromoglicate gel. And other ingredients in this formula wouldn't influence the phase-transition temperature. The content of thermosensitive Sodium Cromoglicate gel for ophthalmic use was determined through UV spectrophotometer according to the requests in Pharmacopeia, and this method was applied for external quality control. The quanlity, pH value, stability and centrifugalization test of this drug were completely in line with requirements. No stimulus was found to rabbit eyes after master single test and successive multiple dosing administration, indicating its safety as a gutta for human eyes.Membraneless dissolution model was employed to investigate the releasing time and gel dissolution, as well as the relationship between releasing time and drug releasing amounts. Satisfactory linearity was found for the relationship between drug releasing amount and gel dissolution, suggesting they released in the same velocity.