title: Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.
abstract: Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.
authors.affiliation: a Department of Pharmacy, Faculty of Medicine , University of Tartu , Tartu , Estonia .
authors.forename: Anna
authors.initials: A
authors.lastname: Penkina
authors.affiliation: a Department of Pharmacy, Faculty of Medicine , University of Tartu , Tartu , Estonia .
authors.forename: Kristian
authors.initials: K
authors.lastname: Semjonov
authors.affiliation: b Department of Chemistry, Faculty of Science , University of Helsinki, Laboratory of Inorganic Chemistry , Helsinki , Finland .
authors.forename: Maija
authors.initials: M
authors.lastname: Hakola
authors.affiliation: b Department of Chemistry, Faculty of Science , University of Helsinki, Laboratory of Inorganic Chemistry , Helsinki , Finland .
authors.forename: Sirpa
authors.initials: S
authors.lastname: Vuorinen
authors.affiliation: b Department of Chemistry, Faculty of Science , University of Helsinki, Laboratory of Inorganic Chemistry , Helsinki , Finland .
authors.forename: Timo
authors.initials: T
authors.lastname: Repo
authors.affiliation: c Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy , University of Helsinki , Helsinki , Finland , and.
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
authors.affiliation: d Institute of Ecology and Earth Sciences, University of Tartu , Tartu , Estonia.
authors.forename: Jaan
authors.initials: J
authors.lastname: Aruväli
authors.affiliation: a Department of Pharmacy, Faculty of Medicine , University of Tartu , Tartu , Estonia .
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
authors.affiliation: a Department of Pharmacy, Faculty of Medicine , University of Tartu , Tartu , Estonia .
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.affiliation: a Department of Pharmacy, Faculty of Medicine , University of Tartu , Tartu , Estonia .
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015925:Cryopreservation / Q000379:methods; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D010894:Piroxicam / Q000032:analysis / Q000737:chemistry*; D011108:Polymers / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004337:Drug Carriers; D011108:Polymers; D014867:Water; D010894:Piroxicam
keywords: Amorphous solid dispersion; dissolution; polyvinylpyrrolidone; pretreated softwood cellulose; solid-state stability