TY - JOUR
T1 - Fast release of liquid antisolvent precipitated fenofibrate at high drug loading from biocompatible thin films
AU - Azad, Mohammad A.
AU - Sievens-Figueroa, Lucas
AU - Davé, Rajesh N.
N1 - Funding Information:
The authors acknowledge financial support from the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems through the grant EEC-0540855. The authors are also grateful to Prof. Rodolfo Romanach for access to Near-IR Chemical Imaging and related data analysis.
Publisher Copyright:
© 2018 The Society of Powder Technology Japan
PY - 2018/12
Y1 - 2018/12
N2 - Motivated by recent papers on nano and micro-particle slurry casting of poorly water-soluble drugs forming biocompatible films with enhanced properties, this work explores incorporation of liquid antisolvent (LAS) precipitated suspensions of fenofibrate, a model poorly soluble drug using both semi-synthetic (HPMC E15 LV) and natural (sodium alginate, SA) polymer as film formers. Centrifugation and subsequent resuspension were employed to minimize residual solvent and increase drug loading (∼20%) in the LAS suspensions and in the film. Film's critical quality attributes (CQAs), including drug distribution and uniformity, mechanical properties, and dissolution were assessed. Crystalline nature of FNB was largely preserved in the film without any polymorphic changes confirmed by XRD, DSC, and Raman. The NIR chemical imaging, corroborated by SEM imaging and drug content relative standard deviation (RSD) indicates that the drug is uniformly distributed without any observable large agglomerates. The films with SA showed lower mechanical strength as compared to HPMC due to SA's low molecular weight. All films exhibited immediate drug release as has been the case using FNB nano particles in previous papers. Interestingly, although addition of plasticizer improved film dissolution, HPMC-based films had a faster dissolution compared to SA-based films in spite of higher mechanical strength of the former.
AB - Motivated by recent papers on nano and micro-particle slurry casting of poorly water-soluble drugs forming biocompatible films with enhanced properties, this work explores incorporation of liquid antisolvent (LAS) precipitated suspensions of fenofibrate, a model poorly soluble drug using both semi-synthetic (HPMC E15 LV) and natural (sodium alginate, SA) polymer as film formers. Centrifugation and subsequent resuspension were employed to minimize residual solvent and increase drug loading (∼20%) in the LAS suspensions and in the film. Film's critical quality attributes (CQAs), including drug distribution and uniformity, mechanical properties, and dissolution were assessed. Crystalline nature of FNB was largely preserved in the film without any polymorphic changes confirmed by XRD, DSC, and Raman. The NIR chemical imaging, corroborated by SEM imaging and drug content relative standard deviation (RSD) indicates that the drug is uniformly distributed without any observable large agglomerates. The films with SA showed lower mechanical strength as compared to HPMC due to SA's low molecular weight. All films exhibited immediate drug release as has been the case using FNB nano particles in previous papers. Interestingly, although addition of plasticizer improved film dissolution, HPMC-based films had a faster dissolution compared to SA-based films in spite of higher mechanical strength of the former.
KW - Biocompatible films
KW - Fenofibrate
KW - Liquid antisolvent precipitation
KW - Poorly soluble drug particles
KW - Semi-synthetic vs natural polymer
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U2 - 10.1016/j.apt.2018.08.024
DO - 10.1016/j.apt.2018.08.024
M3 - Article
AN - SCOPUS:85053623226
SN - 0921-8831
VL - 29
SP - 2907
EP - 2919
JO - Advanced Powder Technology
JF - Advanced Powder Technology
IS - 12
ER -