Budesonide particles

Figure 4 The effect of spacer length on dose dehvery. Fine (< 4.7-pm) and coarse (> 4.7-pm) budesonide particles delivered from a pMDI with a metal spacer of different lengths. The aerosol was analyzed by an Anderson impactor (U.S. throat) 2 s after actuation (28 L/min). The optimal ratio between fine and coarse particles was obtained with a spacer of 13 cm for this particular pMDI. Other pMDIs will have different optimum spacer sizes, depending on vapor pressure.

Fig. 1 (a) Amorphous budesonide particles produced by evaporating an ethanoUc solution of budesonide and hydroxypropylcellulose at atmospheric pressure, (b) Crystalline budesonide particles prepared by addition of water to a sonicated ethanoUc solution of budesonide, (c) Crystalline budesonide particles prepared by addition of water to a sonicated ethanolic solution of budesonide and hydroxypropylcellulose... 

Pulmonary deposition efficiency depends on physicochemical characteristics, such as density of the aerosol or dry powder particles [33-35], Generally, particle diameters less than than 5 pm are required for efficient pulmonary delivery [36, 37], Pulmonary deposition also depends on the nature of the delivery device and differs between metered dose inhalers (MDIs). For example, pulmonary deposition expressed as the ratio of pulmonary versus total (pulmonary + oral) absorbed drug, ranged from 15-55% for a number of salbutamol devices and from 66-85% for drugs with lower oral bioavailabilities such as budesonide. 

A recent novel approach uses the PLGA polymer as a sustained-release coating on budesonide dry powders. Talton et al. showed that these coated particles conferred a statistically significant increase in pulmonary targeting in rats compared with uncoated budesonide powders [101], Another approach uses a wax coating to control particle dissolution. Pillai et al. produced paraffin wax-coated fluores-... 

Electrostatic profiles of drugs before and after aerosolization from commercial Turbohaler and prototype Dryhaler were characterized by Byron, Peart, and Staniforth Fine particle (<5.8pm) charges of budesonide aerosols from Pulmicort Turbohaler were... 

Besides surface texture, excipient particle size also plays an important role in the fine particle generation as shown by budesonide, where the highest fine particle fraction was obtained with small-sized (<32pm) lactose as the carrier. Additionally, fine particle excipients such as fine lactose or polyethylene glycol were reported to improve the performance of carrier-based protein dry powder aerosols.However, there are some cases where carriers improved total powder emission but reduced the percent of active powders in the aerosol. To be useful carriers, the excipients must be physically stable. The important physicochemical characteristics for drug carrier selection are discussed in Ref.t f... 

Martin et al. precipitated budesonide and budesonide-PLA microparticles by a PCA technique. Utilizing SC CO2 as an antisolvent at various temperatures (35°C and 40°C) and pressures (78.9, 85.8, 92.7, and 138 bar), the drug solution and antisolvent were passed coaxially, as drug solution was introduced through a 100-pm capillary tube. Typical experiments involved two 20-1- —sec sprays of budesonide-PLA solution at 1.4mL/min, followed by CO2 equivalent volume purging to remove the residual solvent (methylene chloride). The mean diameters of processed budesonide and budesonide-PLA particles were 1-2 pm. The budesonide-PLA microparticles had a loading of 7.94%, which was equivalent to an 80% encapsulation efficiency. The in vitro release studies indicated a 50% budesonide release from the microparticles at the end of 28 days. The unprocessed budesonide, SCF-processed budesonide, and SCF-processed budesonide-PLA particles are shown in Fig. 5. 

For MDIs, lung deposition can be enhanced by (1) gentle exhalation to residual volume rather than to functional residual capacity, (2) slow inhalation (lOL/min) rather that fast inhalation (50L/min), and (3) breath hold of 10 sec rather than none at end of puff inhalation. These observations were based on measurement of urinary albuterol at 30-min postinhalation, which is considered to reflect lung delivery and to avoid gastrointestinal (GI) tract deposition [36], The effect of inhalation flowrate through an aerosol device can greatly affect particle size, a factor that may explain in part the reduced deposition with suboptimal flowrates. Failure to quickly achieve optimal inspiratory flowrate via a budesonide Turbuhaler can result in an increase in size from <6.6 microns to... 

Pharm S, Wiedmann TS. Note dissolution of aerosol particles of budesonide in Survanta, a model lung surfactant. J Pharm Sci 90(1) 98-104, 2001. 

Turbuhaler DPI, de Boer et al. showed that an increase of 0.5 L/s produced a fine particle fraction of approximately 20%, while a rise of 12 L/s led to a fine particle fraction of approximately 50%. The latter results were independent of the peak flow reached, which varied between 40 and 60 L/min (90). These data have been confirmed by Everard et al. who used a 400-pg budesonide Turbuhaler DPI (91). 

Smaldone GC, Cruz-Rivera M, Nikander K. In vitro determination of inhaled mass and particle distribution for budesonide nebulizing suspension. J Aerosol Med 1998 11 113-125. 

Patients are always instructed to shake their pMDl prior to inhalation because of the potential problem of separation of drug particles from the suspension (21). Berg (22) visually demonstrated the importance of shaking a MDI prior to inhalation. She was able to transfer budesonide suspension from a pMDI to a pMDI with a glass canister that allowed the behavior of the micronized drug sus-... 

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