| Objective:Allergic diseases are one of the most common pediatric diseases in the world,and there are many treatment options for allergic diseases.H1 antihistamines are often recommended for clinical use.As a new second generation of H1 antihistamine,levolcetirizine dihydrochloride not only has less inhibitory effect on the central system of children,but also as the active ingredient of the second generation of antihistamine cetirizine hydrochloride,it can not only ensure the efficacy,but also reduce the dosage by half.However,due to the insufficient development of clinical pharmacology in children and the lack of real-world research evidence,its safety and efficacy still need to be further investigated,and the marketed varieties lack suitable dosage forms and specifications for chldren.Therefore,a meta-analysis was conducted to investigate the efficacy and safety of the drug,and the electronic tongue was used to improve its bitterness.Finally,levocetirizine dihydrochloride orally disintegrating tablets for children with good taste and rapid disintegration in the mouth were prepared by freeze-drying method.Methods:(1)Meta-analysis of levoretirizine dihydrochloride in the treatment of allergic diseases in children:China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP database,China Biology Medicine Disc,SCI,Pubmed,Embase and Cochrane Library were searched.According to inclusion and exclusion criteria,the literatures were screened,and the effectiveness,significant effectiveness and adverse reactions of the included literatures were analyzed.(2)Taste mask of levocetirizine dihydrochloride based on electronic tongue technology:The modern emerging bionic instrument electronic tongue was used to study the taste mask of levocetirizine dihydrochloride.A series of concentrations of berberine hydrochloride solution were selected to train volunteers’ bitter taste sensitivity.After the training,volunteers scored different concentrations of levocetirizine dihydrochloride solution,and the solution with score grade Ⅳ was selected as the intermediate solution to be tested.The electronic tongue signal value was measured,and the principal component analysis and standardized E uclidean distance were calculated to compare the effects of different sweeteners on improving the bitterness of drugs.On the basis of determining the type of sweetener,the types and dosages of different types of cyclodextrins were investigated by the same analytical method,and the inclusion of cyclodextrins was characterized by infrared spectrophotometry,differential scanning calorimetry,and scanning electron microscopy.(3)Preparation of levocetirizine dihydrochloride orally disintegrating tablets for children:The appearance and disintegration time were taken as evaluation indicators,and the type and dosage of skeleton agent and adhesive were determined by single factor investigation.Determine the amount of sweetener by taste;The appearance,disintegration time,texture and taste were used as evaluation indexes,and the formulation was optimized and the process was verified by orthogonal experiments.The freeze-drying curve was optimized based on the eutectic point and the comelting point,and the appearance,disintegration time and water content were evaluated.(4)Quality evaluation of children’s levocetirizine dihydrochloride orally disintegrating tablets:To evaluate the quality of self-made children’s levocetirizine dihydrochloride orally disintegrating tablets in terms of character,disintegration time,disintegration time limit,water content,weight difference,and content uniformity,so as to lay a foundation for the formulation of quality standards in the future.Results:(1)Meta-analysis of levocetirizine dihydrochloride in the treatment of allergic diseases in children:A total of 11 articles were included.Through meta-analysis,seven comparative studies found that levocetirizine dihydrochloride was more effective than other treatment regimens,and the difference was statistically significant.Subgroup analysis by time,five comparative studies found that levocetirizine dihydrochloride was more effective than other treatment regimens at two weeks,and the difference was statistically significant.Three comparative studies found no significant difference in efficacy between levocetirizine dihydrochloride and other treatments at four weeks.In the significant effectiveness analysis,five studies reported at two weeks,and the other three studies reported that the proportion of patients with significant effectiveness of levorcetirizine dihydrochloride was higher than that of other treatment regimens at four weeks,and the difference was statistically significant.For adverse reactions,the comparison of eight literatures found that there was no significant difference in the incidence of adverse events between levocetirizine dihydrochloride and other treatment regimens.(2)The study of levocetirizine dihydrochloride taste mask based on electronic tongue technology:According to the results of artificial taste,levocetirizine dihydrochloride solution with grade Ⅳ and concentration of 1.25 mg·mL-1 was selected as the intermediate solution to be tested.According to principal component analysis and calculation of standardized Euclidean distance,sucralose was determined as sweetener,β-cyclodextrin was selected as cyclodextrin,and the dosage was 8 times.Infrared spectrophotometry,differential scanning calorimetry and scanning electron microscopy were used to characterize the inclusion of cyclodextrin,and it was found that the position of the absorption peak shifted and the morphology changed,indicating that the inclusion was successful.The results were verified by artificial taste test,and the results showed that the bitterness of the drug had been completely masked.(3)Preparation of levcetirizine dihydrochloride orally disintegrating tablets for children:The optimized formulation of lecetirizine dihydrochloride orally disintegrating tablets is lecetirizine dihydrochloride-β-cyclodextrin complex 11.25 mg/tablet,glycine 10 mg/tablet,Pullulan 8 mg/tablet,sucralose 0.5 mg/tablet,and white peach essence 1.5μL/tablet.The prepared orally disintegrating tablets have beautiful appearance,rapid disintegration and good taste.After entering the box,the freeze-drying curve was-40℃ into the box,vacuumed for 30 min,and the vacuum was between 10 and 20 Pa.The temperature of the box was maintained for 60 min,and the temperature was heated to-15℃ for 60 min,and the temperature was heated to-5℃ for 60 min,and the temperature was heated to 25℃ for 60 min.The heating rate of each stage was 1℃·min-1.The prepared mouth crumpling sheet was full,with smooth surface,rapid disintegration,qualified water content,and regular pore arrangement.(4)Quality evaluation of orally disintegrating tablets of levorcetirizine dihydrochloride for children:the prepared orally disintegrating tablets were uniform in color,full in shape,smooth in surface,without core melting and bottom melting,and the pores were arranged regularly and uniform in size.The disintegration time was(2.16±0.38)s.The disintegration time was in line with the provisions of pharmacopoeia.The average tablet weight was 30.40 mg,and the maximum weight difference was 0.81%,which met the requirements.The average water content was 3.823%,less than 5%,which met the requirements.The average content was 1.25 mg/tablet,which was consistent with the labeled amount and conformed to the provisions of pharmacopoeia.Conclusion:To investigate the safety and efficacy of levocetirizine dihydrochloride in the treatment of allergic diseases in children by Meta-analysis,and to provide evidence for doctors in the clinical diagnosis and treatment.By analyzing the signal value measured by electronic tongue,it was determined that sucralose and β-cyclodextrin could well mask the bitter taste of levocetirizine dihydrochloride.Levorcetirizine dihydrochloride orally disintegrating tablets prepared by the freeze-drying method are of qualified quality,rapid disintegration and good taste,which are more conducive to children’s use. |
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