TY - JOUR
T1 - Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions?
AU - Bilgili, Ecevit
AU - Li, Meng
AU - Afolabi, Afolawemi
N1 - Publisher Copyright:
© 2015 Informa Healthcare USA, Inc.
PY - 2016/5/18
Y1 - 2016/5/18
N2 - Ensuring the physical stability of drug nanosuspensions prepared via wet media milling has been a challenge for pharmaceutical scientists. The aim of this study is to assess the combined use of non-ionic cellulosic polymers and anionic surfactants in stabilizing multiple drug nanosuspensions. Particle size of five drugs, i.e. azodicarbonamide (AZD), fenofibrate (FNB), griseofulvin (GF), ibuprofen (IBU) and phenylbutazone (PB) was reduced separately in an aqueous solution of hydroxypropyl cellulose (HPC) with/without sodium dodecyl sulfate (SDS) via a stirred media mill. Laser diffraction, scanning electron microscopy, thermal analysis, rheometry and electrophoresis were used to evaluate the breakage kinetics, storage stability, electrostatic repulsion and stabilizer adsorption. Without SDS, drug particles exhibited aggregation to different extents; FNB and GF particles aggregated the most due to low zeta potential and insufficient steric stabilization. Although aggregation in all milled suspensions was reduced due to HPC-SDS combination, FNB and IBU showed notable growth during 7-day storage. It is concluded that the combination of non-ionic cellulosic polymers and anionic surfactants is generally viable for ensuring the physical stability of wet-milled drug nanosuspensions, provided that the surfactant concentration is optimized to mitigate the Ostwald ripening, whereas cellulosic polymers alone may provide stability for some drug suspensions.
AB - Ensuring the physical stability of drug nanosuspensions prepared via wet media milling has been a challenge for pharmaceutical scientists. The aim of this study is to assess the combined use of non-ionic cellulosic polymers and anionic surfactants in stabilizing multiple drug nanosuspensions. Particle size of five drugs, i.e. azodicarbonamide (AZD), fenofibrate (FNB), griseofulvin (GF), ibuprofen (IBU) and phenylbutazone (PB) was reduced separately in an aqueous solution of hydroxypropyl cellulose (HPC) with/without sodium dodecyl sulfate (SDS) via a stirred media mill. Laser diffraction, scanning electron microscopy, thermal analysis, rheometry and electrophoresis were used to evaluate the breakage kinetics, storage stability, electrostatic repulsion and stabilizer adsorption. Without SDS, drug particles exhibited aggregation to different extents; FNB and GF particles aggregated the most due to low zeta potential and insufficient steric stabilization. Although aggregation in all milled suspensions was reduced due to HPC-SDS combination, FNB and IBU showed notable growth during 7-day storage. It is concluded that the combination of non-ionic cellulosic polymers and anionic surfactants is generally viable for ensuring the physical stability of wet-milled drug nanosuspensions, provided that the surfactant concentration is optimized to mitigate the Ostwald ripening, whereas cellulosic polymers alone may provide stability for some drug suspensions.
KW - Aggregation
KW - Ostwald ripening
KW - bioavailability enhancement
KW - drug nanoparticles
KW - physical stability
KW - wet media milling
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U2 - 10.3109/10837450.2015.1022788
DO - 10.3109/10837450.2015.1022788
M3 - Article
C2 - 25774989
AN - SCOPUS:84960347736
SN - 1083-7450
VL - 21
SP - 499
EP - 510
JO - Pharmaceutical Development and Technology
JF - Pharmaceutical Development and Technology
IS - 4
ER -