title: Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.
abstract: This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.
authors.affiliation: a Department of Pharmacy, Postgraduate Program in Pharmaceutical Sciences , Federal University of Paraná , Curitiba , Brazil ;
authors.forename: Jessica Mendes
authors.initials: JM
authors.lastname: Nadal
authors.affiliation: a Department of Pharmacy, Postgraduate Program in Pharmaceutical Sciences , Federal University of Paraná , Curitiba , Brazil ;
authors.forename: Mona Lisa Simionatto
authors.initials: ML
authors.lastname: Gomes
authors.affiliation: b Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences , State University of Ponta Grossa , Ponta Grossa , Brazil ;
authors.forename: Débora Maria
authors.initials: DM
authors.lastname: Borsato
authors.affiliation: c Department of Chemistry, Postgraduate Program in Chemistry , Federal University of Paraná , Curitiba , Brazil.
authors.forename: Martinha Antunes
authors.initials: MA
authors.lastname: Almeida
authors.affiliation: b Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences , State University of Ponta Grossa , Ponta Grossa , Brazil ;
authors.forename: Fernanda Malaquias
authors.initials: FM
authors.lastname: Barboza
authors.affiliation: c Department of Chemistry, Postgraduate Program in Chemistry , Federal University of Paraná , Curitiba , Brazil.
authors.forename: Sônia Faria
authors.initials: SF
authors.lastname: Zawadzki
authors.affiliation: b Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences , State University of Ponta Grossa , Ponta Grossa , Brazil ;
authors.forename: Paulo Vitor
authors.initials: PV
authors.lastname: Farago
authors.affiliation: a Department of Pharmacy, Postgraduate Program in Pharmaceutical Sciences , Federal University of Paraná , Curitiba , Brazil ;
authors.forename: Sandra Maria Warumby
authors.initials: SM
authors.lastname: Zanin
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects; D003373:Coumaric Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003890:Desiccation / Q000379:methods*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000975:Antioxidants; D003373:Coumaric Acids; D004337:Drug Carriers; D005079:Excipients; D010975:Platelet Aggregation Inhibitors; D011092:Polyethylene Glycols; C004999:ferulic acid
keywords: Antioxidant; hydrophilic carrier; phytoalexin; platelet aggregation; spray-drying