Inhalable Ipratropium Bromide Particle Engineering with Multicriteria Optimization
Spray-dried ipratropium bromide (IPB) microspheres for oral inhalation were engineered using Quality by Design. The interrogation of material properties, process parameters, and critical product quality attributes interplay enabled rational product design. A 2 7–3 screening design exhibited the Mail...
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Published in | AAPS PharmSciTech Vol. 18; no. 6; pp. 1925 - 1935 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.08.2017
|
Subjects | |
Online Access | Get full text |
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Summary: | Spray-dried ipratropium bromide (IPB) microspheres for oral inhalation were engineered using Quality by Design. The interrogation of material properties, process parameters, and critical product quality attributes interplay enabled rational product design. A 2
7–3
screening design exhibited the Maillard reaction between L-leucine (LL) and lactose at studied outlet temperatures (OT) >130°C. A response surface custom design was used in conjunction with multicriteria optimization to determine the operating design space to achieve inhalable microparticles. Statistically significant predictive models were developed for volume median diameter (
p
= 0.0001, adjusted
R
2
=
0.9938), span (
p
= 0.0278, adjusted
R
2
=
0.7912), yield (
p
= 0.0020, adjusted
R
2
=
0.9320), and OT (
p
= 0.0082, adjusted
R
2
=
0.8768). An independent verification batch confirmed the model’s predictive capability. The prediction and actual values were in good agreement. Particle size and span were 3.32 ± 0.09 μm and 1.71 ± 0.18, which were 4.7 and 5.3% higher than the predicted values. The process yield was 50.3%, compared to the predicted value of 65.3%. The OT was 100°C
versus
the predicted value of 105°C. The label strength of IPB microparticles was 99.0 to 105.9%
w
/
w
suggesting that enrichment occurred during the spray-drying process. The present study can be utilized to initiate the design of the first commercial IPB dry powder inhaler. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1530-9932 1530-9932 |
DOI: | 10.1208/s12249-016-0668-y |