TY - JOUR
T1 - Critical Material Attributes of Strip Films Loaded With Poorly Water-Soluble Drug Nanoparticles
T2 - II. Impact of Polymer Molecular Weight
AU - Krull, Scott M.
AU - Ammirata, Jennifer
AU - Bawa, Sonia
AU - Li, Meng
AU - Bilgili, Ecevit
AU - Davé, Rajesh N.
N1 - Publisher Copyright:
© 2017 American Pharmacists Association®
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Recent work established polymer strip films as a robust platform for delivery of poorly water-soluble drug particles. However, a simple means of manipulating rate of drug release from films with minimal impact on film mechanical properties has yet to be demonstrated. This study explores the impact of film-forming polymer molecular weight (MW) and concentration on properties of polymer films loaded with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a model Biopharmaceutics Classification System class II drug, were prepared in aqueous suspension via wet stirred media milling. Aqueous solutions of 3 viscosity grades of hydroxypropyl methylcellulose (14, 21, and 88 kDa) at 3 viscosity levels (∼9500, ∼12,000, and ∼22,000 cP) were mixed with drug suspension, cast, and dried to produce films containing griseofulvin nanoparticles. Few differences in film tensile strength or elongation at break were observed between films within each viscosity level regardless of polymer MW despite requiring up to double the time to achieve 100% drug release. This suggests film-forming polymer MW can be used to manipulate drug release with little impact on film mechanical properties by matching polymer solution viscosity. In addition, changing polymer MW and concentration had no negative impact on drug content uniformity or nanoparticle redispersibility.
AB - Recent work established polymer strip films as a robust platform for delivery of poorly water-soluble drug particles. However, a simple means of manipulating rate of drug release from films with minimal impact on film mechanical properties has yet to be demonstrated. This study explores the impact of film-forming polymer molecular weight (MW) and concentration on properties of polymer films loaded with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a model Biopharmaceutics Classification System class II drug, were prepared in aqueous suspension via wet stirred media milling. Aqueous solutions of 3 viscosity grades of hydroxypropyl methylcellulose (14, 21, and 88 kDa) at 3 viscosity levels (∼9500, ∼12,000, and ∼22,000 cP) were mixed with drug suspension, cast, and dried to produce films containing griseofulvin nanoparticles. Few differences in film tensile strength or elongation at break were observed between films within each viscosity level regardless of polymer MW despite requiring up to double the time to achieve 100% drug release. This suggests film-forming polymer MW can be used to manipulate drug release with little impact on film mechanical properties by matching polymer solution viscosity. In addition, changing polymer MW and concentration had no negative impact on drug content uniformity or nanoparticle redispersibility.
KW - UV/vis spectroscopy
KW - biodegradable polymers
KW - content uniformity
KW - controlled release/delivery
KW - dissolution rate
KW - formulation
KW - nanoparticles
KW - particle sizing
KW - polymeric drug delivery systems
KW - thermogravimetric analysis
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U2 - 10.1016/j.xphs.2016.10.009
DO - 10.1016/j.xphs.2016.10.009
M3 - Article
C2 - 27871727
AN - SCOPUS:85006891561
SN - 0022-3549
VL - 106
SP - 619
EP - 628
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 2
ER -