Bran Furoate Nasal Ie, Gel Spray Developed

Mometasone furoate(MF) is one of several intranasal corticosteroids. The marketing dosage form is mometasone furoate nasal spray which is accepted as safe and effective first-line therapy for allergic rhinitis. At present MF nasal spray on the market is suspension, but the therapeutic effect of MF is influenced by the rapid elimination of the instilled drug from the nasal cavity by mucociliary beating. Therefore, developing new intranasal dosage form of MF to get better therapeutic effect has a good application perspective of treating allergic rhinitis. In situ gel that refers to the polymer solutions can be prepared and administrated as liquid, which undergo a phase transition to a semisolid gel upon exposure to physiological environments. Because in situ gel has the advantages of both solution and gel, it has a broad application prospect in the research of drug carrier field. In this dissertation, gellan gum was selected as gel base, and mometasone furoate was selected as a model drug, then the MF nasal in situ gel spray was developed based on the concept of ion-activated. The composition of MF dosage form, preparation process, quality analysis and control, nasal cavity irritation and pharmacodynamics were evaluated in vitro and in vivo.In the first part of this dissertation, deacetylated gellan gum(DGG) was selected as ion-sensitive gelling material. Rheological character of different concentration of DGG was evaluted, and results showed DGG solution was pseudoplastic fluids, which displayed decreasing viscosity with increasing shear rate. When contacting with artifical nasal fluids, the DGG solution turns to a semisolid gel at once and shows higher viscosity than the solution. The in vitro biodegradation test showed DGG was resistant to enzymatic degradation by lysozym which is naturally present in mucus. All results indicated that 0.5% DGG solution was most apporpriate to prapare in situ gel, displaying suitable ion sensitivity and avoiding difficult preparation due to high viscosity.In the second part of this dissertation, the proportion of suspending agent xanthan gum and wetting agent glycerol were screening by orthogonal experiment which the deacetylated gellan gum was gel base. According to the character of active substance and mucus, the composition and preparation of MF nasal in situ gel spray were determined. The quality of MF nasal in situ gel spray was evaluated, and the assay of content and related substance for MF product has high specificity and is operated simply through HPLC.In the third part of this dissertation, a model of allergic rhinitis rats was established to evaluate MF product therapeutic efficacy and the safety and ciliary toxicity of MF product to toad palate was also evaluated. The animal experiment suggested that MF in situ gel could be more effective than the nasal suspension on the marketing in the treatment of allergic rhinitis to decrease the degree of sneezing, and could keep therapeutic effect up to 9 hours. Examination results of the nasal cavity of in situ gel showed intact ciliated respiratory epithelium and normal goblet cell appearance for 35 days treatment to Wistar rats. The micrographic results showed that in situ gels were safe, without nasal ciliotoxicity to toad palate.In the fourth part of this dissertation, the stability of Mometasone Furoate in situ gel was studied. The product with marketing container showed a good stability in accelerated and long-term study. The product should use amber glass bottle to protect from light and store at 2～25℃to decrease the influence of high temperature.To sum up, the preparation process of Mometasone Furoate in situ gel is simple, robust, and controled. The quality and stability of MF product is good. Mometasone Furoate in situ gel has the promising therapeutic effects in clinical application.