| Allergic rhinitis(AR)is one of the most common chronic diseases of human,spreading all over the world,among races and ages.The major clinical manifestations are sneezing,nasal congestion,itchy eyes,noses and olfactory dysfunction and other symptoms.With the development of the condition,there might also be accompanied by loss of memory,diminished sense of taste and concurrent pharyngitis,bronchial asthma,sinusitis and nasal polyps and other illnesses.Although there are a variety of drugs of the treatment on allergic rhinitis,corticosteroid drugs(such as budesonide)is considered to be the most effective one,which is widely applied to clinical practice.We develop a quality-stable budesonide nasal spray and have researched the quality and experience the local safety in this paper,while budesonide is treated as main drug,nasal spray as fomulations,and potassium sorbate,polysorbate-80,glucose,EDTA-2Na,micro-crystalline cellulose-sodium carboxymethyl cellulose as accesso-ries.Research works are as follows:Prescription research process:gather relevant information to determine the optimal dosage and prescription form,select suitable solvent,preservatives,pH modifiers,isotonic adjusting agents and suspending agents,take the import drugs appearance,pH,content,viscosity,particle size and so on as preliminary evaluation indicator,to assess and screen the amount of each excipient.With the specific amount of microcrystalline cellulose-sodium carboxy-methyl cellulose,EDTA-2Na and potassium sorbate,which are not determined,we choose four factors and three levels orthogonal experiment investigated to study the suitable matrix formulation and pick out the optimal prescription which can conform the eva-luation criteria in stability test.Results:The nasal spray system is stable with moderate viscosity.The optimal formulation are composed of budesonide 0.128%(w/v),Tween80 0.1%(w/v),colloidal microcrystalline cellulose Avicel~?1.5%(w/v),EDTA-2Na 0.06%(w/v),potassium sorbate 0.12%(w/v),anhydrous glucose 5%(w/v),hydro-chloric acid(amount)and purified water(amount).Quality standards:according to the dosage characteristics of budesonide nasal spray and the relevant requirements of imported drug registration standards,we have its characters,identifycation,content,related substances and other areas as main evaluation,validated the methodology of determination method of budesonide,preservatives and related substances.By using high performance liquid chromatography to determine the content of budesonide,preservative content,the per spray content of main drug and related substances content,we set a suit of comprehensive controllable quality testing methods of budesonide nasal spray and provide basis for enlarging the production and application of the promotion of the preparation.The results show that the mainly indicators of developed budesonide nasal spray are in line with regulations.Preliminary stability:We design drug formulation and test the stability of active ingredients of budesonide nasal spray under 4aspects:influencing factors,accelerated testing for 6 months,6months open packaging test and 9 months long-term test.The results show that the budesonide nasal spray we made is in stable condition under all the factors.The results of accelerated testing,long-term test and open the packaging test also show that budesonide nasal spray has the attributes of stability,storage conditions for dark and at room temperature below 30?.Finally,by using the maximum dose of nasal irritation test for rabbits and guinea pig skin topical sensitization test,we observe the security of drug local effects.The results show that the budesonide nasal spray has no significant toxicity and irritation,conforms with the security requirements of topical agents,is safe and reliable in clinical practice. |
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