title: Redispersible fast dissolving nanocomposite microparticles of poorly water-soluble drugs.
abstract: Enhanced recovery/dissolution of two wet media-milled, poorly water-soluble drugs, Griseofulvin (GF) and Azodicarbonamide (AZD), incorporated into nanocomposite microparticles (NCMPs) via fluidized bed drying (FBD) and spray-drying (SD) was investigated. The effects of drying method, drug loading, drug aqueous solubility/wettability as well as synergistic stabilization of the milled suspensions on nanoparticle recovery/dissolution were examined. Drug nanoparticle recovery from FBD and SD produced NCMPs having high drug loadings was evaluated upon gentle redispersion via optical microscopy and laser diffraction. During wet-milling, hydroxypropyl cellulose (HPC) alone stabilized more wettable drug (AZD) nanoparticles with slight aggregation, but could not prevent aggregation of the GF nanoparticles. In contrast, well-dispersed, stable nanosuspensions of both drugs were produced when sodium dodecyl sulfate (SDS) and HPC were combined. The FBD and SD NCMPs without SDS exhibited incomplete nanoparticle recovery, causing slower dissolution for GF, but not for AZD, likely due to higher aqueous solubility/wettability of AZD. For high active loaded NCMPs (FBD ∼50 wt%, SD ∼80 wt%) of either drug, HPC-SDS together owing to their synergistic stabilization led to fast redispersibility/dissolution, corroborated via optical microscopy and particle sizing. These positive attributes can help development of smaller, high drug-loaded dosage forms having enhanced bioavailability and better patient compliance.
authors: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
authors: Anagha
authors: A
authors: Bhakay
authors: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
authors: Mohammad
authors: M
authors: Azad
authors: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
authors: Ecevit
authors: E
authors: Bilgili
authors: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA. Electronic address: dave@njit.edu.
authors: Rajesh
authors: R
authors: Dave
mesh_terms: D001391:Azo Compounds / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006118:Griseofulvin / Q000008:administration & dosage* / Q000737:chemistry; D053761:Nanocomposites; D053758:Nanoparticles; D010316:Particle Size; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013535:Suspensions; D014867:Water / Q000737:chemistry; D017155:Wettability
chemical_list: D001391:Azo Compounds; D005079:Excipients; D013535:Suspensions; D014867:Water; D006118:Griseofulvin; D012967:Sodium Dodecyl Sulfate; C004525:azodicarbonamide; D002482:Cellulose; C008079:hydroxypropylcellulose
keywords: Fast dissolution; Fluidized bed coating; Nanoparticles; Redispersion; Spray drying; Wet media milling