Study On Nervonic Acid Dry Emulsion Preparation

Objective:The purpose of this experiment is to study on nervonic acid dry emulsion preparation,and to conduct quality evaluation and stability research on the nervonic acid dry emulsion preparation.In the light of the low solubility of nervonic acid and the instability of the emulsion,the excipients and process parameters were optimized to prepare the nervonic acid dry emulsion preparation that meets the requirements,which provided a reference for the development and application of nervonic acid.Methods:Using nervonic acid as raw material,nervonic acid was prepared into nervonic acid emulsion by mechanical method,and then it was made into nervonic acid dry emulsion preparation by freeze-drying method.Taking the appearance of the emulsion,the centrifugal stability of the emulsion,the centrifugal stability constant(Ke)of the emulsion,and the particle size of the emulsion as evaluation indicators,single-factor experiments were used to screen the appropriate types and amounts of oil phase,emulsifier,and co-emulsifier.The optimal dosage of excipients was selected by orthogonal experiment;single factor experiment was used to investigate the effects of emulsification temperature,stirring speed,stirring time,shearing speed,shearing time,high-pressure homogenization pressure and times of homogenization on the appearance of the emulsion,centrifugation stability of the emulsion,Ke value of the emulsion,particle size of the emulsion,combined with the orthogonal experiment to optimize the best process preparation conditions and to prepare the nervonic acid emulsion of all the indexes meet the requirements.Taking the appearance of the emulsion,the redispersibility of the emulsion,and the particle size after reconstitution of nervonic acid dry emulsion preparation as evaluation indicators,experiments were used to screen out suitable proppant types and concentrations,freeze-drying process conditions,and then the emulsion was made into dry emulsion preparation by freeze-drying technology.The appearance,morphological changes,TLC identification,pH value,particle sizes,PDI,Zeta potentials and in vitro dissolution of nervonic acid dry emulsion preparation were investigated,and a high performance liquid chromatography(HPLC)analytical method for determining the content and dissolution of nervonic acid dry emulsion preparation was established.A stability study was carried out on the nervonic acid dry emulsion preparation,and the influence of high temperature environment and high humidity environment on the nervonic acid dry emulsion preparation was investigated,and the nervonic acid dry emulsion preparation was placed at room temperature for 3 months to observe the changes in its properties and content.Results:According to the single factor experiment and orthogonal experiment,the optimal dosage and preparation technology of nervonic acid emulsion were optimized:the dosage of oleic acid was 5%,the dosage of emulsifier op-10 was 4%,and the dosage of propylene glycol was 2%;Emulsify for 5 minutes at a temperature of 60℃ and a stirring speed of 400 r/min,and then using a shearing emulsifying machine with a shearing speed of 4000 r/min for 2 minutes to make colostrum,and then the colostrum was passed through a high-pressure homogenizer under a pressure of 400bar and was circulated 2 times,then the nerve acid emulsion was obtained.The appearance of the prepared nervonic acid emulsion is uniform milky white,no stratification when stationary,no wall hanging phenomenon,no stratification phenomenon after centrifugation at 4000 r/min for 15 minutes,measured their particle sizes of the three batches were 155.44、158.31、160.40 nm.Then,the emulsion was made into a dry emulsion preparation by freeze-drying technology,and the type and concentration of proppant and freeze-drying conditions were screened out:taking 2 mL of nervonic acid emulsion,adding 7.5%(W/W)lactose in the emulsion,shaking to dissolve,and under the conditions of pre-freezing temperature-50℃ for 4 hours,main drying for 60 hours,and final drying for 10 hours,and then the nervonic acid dry emulsion preparation was obtained.The nervonic acid dry emulsion preparation is a white powder with a smooth and firm appearance,and it can be rapidly dissolved and have good fluidity after being reconstituted with water.After reconstitution,the particle sizes of the three batches of nervonic acid dry emulsion preparation were 207.14、208.84、207.50 nm,PDI were 0.226、0.224、0.235,and Zeta potentials were(-30.82)、(-31.75)、(-30.28)mV.The pH values of the three batches of nervonic acid dry emulsion preparation were 4.61、4.61and 4.62.The established HPLC analysis method of nervonic acid dry emulsion preparation is highly specific,and its precision,repeatability,stability and sample recovery rate all meet the methodological requirements.The contents of the three batches of nervonic acid dry emulsion preparation were 44.40、43.66 and 44.90 mg/g.The nervonic acid dry emulsion preparations were basically dissolved in pH6.8 0.5%SDS phosphate buffer for 10 minutes,and only 46.66%of nervonic acid raw materials were dissolved in 120 minutes.In the high temperature test,the appearance and content of the nervonic acid dry emulsion preparation changed significantly,and the color of its appearance deepened,and the content decreased.There is no obvious change in appearance and content after being placed in an environment where relative humidity was 90.0%±5%for 10 days.Three batches of nervonic acid dry emulsion preparation were placed at room temperature for 3 months,and there was no obvious change in appearance,all were uniform milky white,and the content changed inconspicuously.Conclusions:The appearance,the redispersibility,TLC identification and the particle size、PDI、Zeta potentials after reconstitution and the pH value of nervonic acid dry emulsion preparation which was prepared according to the optimal dosage and preparation conditions all meet the requirements.The HPLC analysis method of nervonic acid dry emulsion preparation can be used to determine the content and dissolution of nervonic acid dry emulsion preparation.The in vitro dissolution rate of nervonic acid in the nervonic acid dry emulsion preparation is significantly improved,which is much higher than the nervonic acid raw material,indicating that the nervonic acid can be made into the nervonic acid dry emulsion preparation to solve the problem of low dissolution rate.The stability influencing factor experiment showed that the dry emulsion preparation of nervonic acid has no obvious change in a high-humidity environment during a short term,and the appearance and the content changed significantly in a high-temperature environment,so it should be avoided to be placed in a high-temperature environment.Preliminary stability experiment showed that the nervonic acid dry emulsion preparation had good stability when placed at room temperature for 3 months.And it provides reference for the research and application of nervonic acid dosage forms.