title: Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.
abstract: The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs.
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Sophia Yui Kau
authors.initials: SY
authors.lastname: Fong
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Asiye
authors.initials: A
authors.lastname: Ibisogly
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: annette.bauer@sdu.dk.
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
mesh_terms: D000068579:Celecoxib / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005612:Freeze Drying; D010743:Phospholipids / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D010743:Phospholipids; D014867:Water; D000068579:Celecoxib
keywords: Amorphous solid dispersion; Celecoxib; Freeze-drying; Solid phospholipid nanoparticles; Solubility; Spray-drying