title: Enhanced physical stabilization of fenofibrate nanosuspensions via wet co-milling with a superdisintegrant and an adsorbing polymer.
abstract: Drug nanoparticles in suspensions can form aggregates leading to physical instability, which is traditionally mitigated using soluble polymers and surfactants. The aim of this paper was to explore common superdisintegrants, i.e., sodium starch glycolate (SSG), croscarmellose sodium (CCS), and crospovidone (CP), as novel class of dispersants for enhanced stabilization of fenofibrate (FNB), a model BCS Class II drug, suspensions. FNB was wet-milled with superdisintegrants along with hydroxypropyl methylcellulose (HPMC), a soluble adsorbing polymer, in a stirred media mill. For comparison, FNB was also milled in the presence of HPMC and/or SDS (sodium dodecyl sulfate) without superdisintegrants. Laser diffraction, scanning electron microscopy, viscometry, differential scanning calorimetry, and powder X-ray diffraction were used to characterize the suspensions. The results show that 2% HPMC along with 1% SSG or 1% CCS mitigated the aggregation of FNB nanoparticles significantly similar to the use of either 5% HPMC or 1% HPMC-0.075% SDS, whereas CP was not effective due to its low swelling capacity. CCS/SSG enhanced steric-kinetic stabilization of the FNB suspensions owing to their high swelling capacity, viscosity enhancement, and physical barrier action. Overall, this study provides a mechanistic basis for a novel method of formulating surfactant-free drug nanosuspensions with co-milled superdisintegrants.
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Azad
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Afolawemi
authors.initials: A
authors.lastname: Afolabi
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Anagha
authors.initials: A
authors.lastname: Bhakay
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leonardi
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Davé
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: bilgece@njit.edu.
authors.forename: Ecevit
authors.initials: E
authors.lastname: Bilgili
mesh_terms: D000327:Adsorption; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D011345:Fenofibrate / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000737:chemistry*; D065347:Hypromellose Derivatives / Q000737:chemistry*; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D000960:Hypolipidemic Agents; D013535:Suspensions; D065347:Hypromellose Derivatives; D013213:Starch; C048390:sodium starch glycolate; D011205:Povidone; D002266:Carboxymethylcellulose Sodium; D011345:Fenofibrate
keywords: Drug nanoparticles; Physical stability; Superdisintegrants; Surfactant-free; Swelling; Wet media milling