| Background:Montelukast sodium is a leukotriene receptor antagonist.Montelukast sodium is safe and effective in the treatment of childhood bronchial asthma and allergic rhinitis,it has a rich clinical application base.This study designs an oral fast dissolving film to enhance pediatric patients’ medication compliance,it is based on clinical needs and has important clinical significance.Objective:To study the prescription composition and preparation process of montelukast sodium oral fast dissolving film in treatment of children with bronchial asthma and allergic rhinitis,to conduct a comprehensive quality evaluation of the product.Methods:(1)The analytical method of the relative substance and dissolution are established,refer to the import standard of Singulair chewable tablet.(2)The composition of the prescription and packaging are screened and determined by indicators about film forming properties,appearance traits,disintegration time and related substances.(3)The key process steps,process parameters range,and central control indicators are establishedthrough a detailed study of the whole process.(4)Prescription composition and process parameters are verified through three 15,000 pieces batches enlargement.(5)The related substances,disintegration time and dissolution curve between the self-made film and the RLDs(Singulair chewable tablet/granule,Korea SK film)are compared.(6)The accelerated and long-term stability of the self-made film is investigated.Results:(1)The relative substance is using a linear gradient elution method,the chromatographic conditions are phenyl-bonded silica gel filler,column temperature is 30℃,detection wavelength is 255 nm,flow rate is 1.0mL/min,injection volume is 20μL,mobile phase A is0.2% trifluoroacetic acid aqueous solution,mobile phase B is 0.2% trifluoroacetic acid inacetonitrile solution,separation and detection ability of the analytical method is stronger than the import standard.The analytical methods for the relative substance and dissolution are verified by methodologies,and each validation project meets the requirements of the Chinese Pharmacopoeia.(2)The product prescription is made of PVA-PEG/PVA as film-forming materials,starch as thickening agent,sucralose as the reagent,cochineal as colorant,water as solvent,it is packaged in a PET/AL/PE medicinal composite membrane and filled with nitrogen.(3)The main steps are weighing,preparation of slurry,coating and drying,sub-dose and packaging.The starch slurry is prepared by heating and stirring at 80±5°C.Slurry preparation parameters are stirring 20~60min in 1000 rpm,then vacuum to-0.07Mpa~-0.09 Mpa,stirring and holding pressure 4h;coating speed is 16~18rpm,drying temperature is 60±5℃;the coating thickness is 70±5μm;the moisture content is 4.0 to 8.0%.The main control indicators are traits,content uniformity,moisture,etc.,RSD of content uniformity should be less than 5% and moisture should be between 4.0~8.0%.(4)Producting three batches of pilot samples,each volume is 15,000,according to the established prescription and process,the processesare smooth,the intermediate products and finished products are in line with quality standards.(5)Compared with the RLDs,the result shows that the total amount and the number of impurities in the self-made film are small,the self-made film can be quickly disintegrated in different pH dissolution medium which meet the requirement of instantaneous demand,moreover,the self-made film has obvious advantages.(6)The stability investigation showed that the stability of the self-made film is good.Conclusion:It is proved that the montelukast sodium oral fast dissolving film in children with asthma and allergic rhinitis is simple,reasonable,feasible,controllable and good stability,after prescription screening,pilot enlargement and quality study.It provides scientific research basis for the mass production and clinical research for later. |
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