title: A novel formulation for solubility and content uniformity enhancement of poorly water-soluble drugs using highly-porous mannitol.
abstract: The present study investigates the enhancement of the dissolution rates for poorly-water soluble drugs by a new adsorption method. The results show that the current adsorption method enhanced the dissolution rate of both nifedipine and indomethacin to a significant extent by nano-confinement of drugs into the pore spaces of highly-porous excipients. Porous mannitol particles with a surface area and pore volume of 6.3 ± 0.1 m(2) g(-1) and 0.036 ± 0.002 ml g(-1), respectively, were drug loaded in two different concentrations of indomethacin and nifedipine. The results of drug loading for nifedipine showed an increase from 3.2 ± 0.1% w/w for a 0.08 M drug solution to 9.1 ± 0.3% w/w drug loading for a 0.16 M drug solution, while indomethacin had slightly better performance for the adsorption process, with 4.1 ± 0.2% w/w and 12.6 ± 0.4% w/w for 0.08 M and 0.16 M concentrations of indomethacin, respectively, in the final formulation. This result also indicated highly-uniform blends with a percentage relative standard deviation of less than 4% for drug-loaded mannitol in both nifedipine and indomethacin. This method gave a significant enhancement of the dissolution rate for both drugs due to nano-confinement of drugs into porous excipients and high solubility of porous mannitol, with 80% drug release within the first 15 min for the drug-loaded samples.
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia. Electronic address: morteza.saffari@sydney.edu.au.
authors.forename: Morteza
authors.initials: M
authors.lastname: Saffari
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia.
authors.forename: Amirali
authors.initials: A
authors.lastname: Ebrahimi
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Langrish
mesh_terms: D000327:Adsorption; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D007213:Indomethacin / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry*; D009543:Nifedipine / Q000737:chemistry*; D016062:Porosity; D012995:Solubility
chemical_list: D005079:Excipients; D008353:Mannitol; D009543:Nifedipine; D007213:Indomethacin
keywords: Adsorption; High-porosity mannitol; Indomethacin; Nifedipine; Poorly water-soluble drug; Templating process