Preparation And In Vitro Evaluation Of Budesonide Inhalation Nano-suspension

Budesonide Inhalation Nano-Suspension(BUDINS)was prepared by controlled crystallization method using water as the dispersion medium,and the formulation was optimized with several stabilizing agents.A systemic in-vitro evaluation of BUDINS was conducted after nebulization using the self-made vibrating mesh nebulizer and the commercial Pari nebulizer,respectively.HPLC determination methods for assay and related substances of BUD were established and verified.The processing parameters for preparation of BUD nano-crystals and the optimal formulation of the BUD inhalation nano-suspension was were obtained by screening with the average particle size of BUD and the accumulated percentage of BUD particles less than 1?m as indexes,and the stability of the nano-suspension and the nebulization feasibility were studied as well.The type of stabilizer(0.02% Tween 80,0.01% HPMC,0.01% EDTA-2Na),pH(6.0)and osmotic pressure regulator(0.9% NaCl)were finally determined.The stability of BUDINS was conducted at 40? for 4 months and 25? for 6 months,and no significant difference was observed with regard to the particle size of BUD,p H,BUD content and related substances.The in-vitro aerosolization performance of the preparation was evaluated afte r atomization with two kinds of nebulizers.Firstly,the aerodynamic particle size distribution(APSD)and the fine particle fraction(FPF)of BUDINS atomized by self-made vibrating mesh nebulizer was measured using time of flight(TOF)aer odynamic particle size analyzer,glass twin impinger and next generation impactor(NGI).Secondly,the atomization performance of BUDINS was estimated after ne bulization with the commercial Pari nebulizer,which was compared with that of the commercially available budesonide suspension(BUDIS,Pulmicort)with the p ercentage of drug residues,APSD and FPF as main indicators.Finally,the effect s of inspiratory mode and flow velocity on the results of atomization of BUDIN S by self-made vibrating net atomizer were investigated.The results showed th at the mass median diameter(MMAD)of the aerosol droplet was(1.87 ± 0.01)?m and the geometric standard deviation(GSD)was(1.52 ± 0.00)measured by TOF;the FPF<6.4?m of BUDINS was(94.89±1.35)% determined by glass twin i mpinger;MMAD of BUDINS atomized by self-made vibrating-mesh nebulizers w as(3.24±0.06)?m,GSD was(2.14±0.06);MMAD of BUDINS atomized by Pari n ebulizers was(3.16±0.10)?m,GSD was(2.60±0.10);MMAD of BUDIS atomized by Pari nebulizers was(4.20±0.11)?m,GSD was(2.80±0.55)measured by NGI.A t the same time,the drug residue fraction of BUDINS atomized b-y self-made vi brating mesh nebulizer measured was(22.67 ± 0.87)%,while that of BUDINS at omized by Pari nebulizer was(48.73±4.71)%,BUDIS atomized by Pari nebulizer was(64.17±4.74)%.The results show that the residual fraction of the self-made vibrating mesh nebulizer is much smaller than that of the Pari nebulizer.The FP F of the former is much higher than that of the latter,and the aerosol particle s ize distribution is more uniform for the former.The MMAD of BUDINS atomi zed by self-made vibrating mesh nebulizer and Pari nebulizer is much smaller th an that of BUDIS atomized by Pari nebulizer.The budesonide inhalation nano-suspension prepared in this study can be smoothly atomized by the self-made vibrating-mesh nebulizer.The aerosol droplet distribution of the BUD nano-suspension after atomization is more uniform,and the percentage of drug delivery is much higher than that of the commercial BUD suspension.Thus,it is expected to reduce the dose and therefor the side effects of drugs with the BUD nano-suspension instead of the ordinary suspension,and to shorten the treatment time and improve patient compliance as well with the novel nebulizer.