title: Formulation design and evaluation of amorphous ABT-102 nanoparticles.
abstract: Amorphous nanoparticles are able to enhance the kinetic solubility and concomitant dissolution rates of BCS class II and BCS class II/IV molecules due to their characteristic increased supersaturation levels, smaller particle size and greater surface area. A DoE approach was applied to investigate formulation and spray drying process parameters for the preparation of spray dried amorphous ABT-102 nanoparticles. Stability studies were performed on the optimized formulations to monitor physical and chemical changes under different temperature and humidity conditions. SLS/soluplus and SLS/PVP K25 were the best stabilizer combinations. Trehalose was used to prevent nanoparticle aggregation during spray drying. Particle size distribution, moisture content, PXRD, PLM, FTIR and in vitro dissolution were utilized to characterize the spray dried nanoparticle formulations. The formulations prepared using soluplus showed enhanced dissolution rate compared to those prepared using PVP K25. Following three months storage, it was observed that the formulations stored at 4°C were stable in terms of particle size distribution, moisture content, and crystallinity, whereas those stored at 25°C/60%RH and 40°C/75%RH were unstable. A predictive model to prepare stable solid spray dried amorphous ABT-102 nanoparticles, incorporating both formulation and process parameters, was successfully developed using multiple linear regression analysis.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Rajan
authors.initials: R
authors.lastname: Jog
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Global Pharmaceutical R&D, AbbVie Pte. Ltd., 138667, Singapore.
authors.forename: Nital
authors.initials: N
authors.lastname: Jugade
authors.affiliation: Global Pharmaceutical R&D, AbbVie Pte. Ltd., 138667, Singapore.
authors.forename: David Cheng Thiam
authors.initials: DC
authors.lastname: Tan
authors.affiliation: Global Pharmaceutical R&D, AbbVie Pte. Ltd., 138667, Singapore.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gokhale
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States. Electronic address: d.burgess@uconn.edu.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007191:Indazoles / Q000138:chemical synthesis*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014961:X-Ray Diffraction
chemical_list: C528492:ABT 102; D007191:Indazoles; D014508:Urea
keywords: Amorphous nanoparticles; DoE; In vitro dissolution testing; Spray drying