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.

Optimized synthesis of novel prenyl ferulate performed by feruloyl esterases from Myceliophthora thermophila in microemulsions

“…As shown in Fig. 7, FA reduced significantly the intracellular levels of ROS in a concentration-dependent manner, in accordance with previous data from a murine macrophage cell line (Nadal et al 2016). PFA also provoked a reduction of intracellular ROS at concentrations ranging from 4 to 20 μM, while at 100 μM, no significant antioxidant effect was observed.

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Preparation of Poloxamer188-b-PCL and Study on in vitro Radioprotection Activity of Curcumin-Loaded Nanoparticles

“…The first event was observed at 300-350 • C with a mass loss of 50%, which was assigned to the decomposition of poloxamer188 chains (Abdelrazek et al, 2016). The event at 370-410 • C (mass loss of 15%) was due to the thermal rupture of PCL chains (Nadal et al, 2016). The differences between both curves indicated that poloxamer188-b-PCL had better thermostability than original poloxamer188.…”

Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

“…The mechanism of ferulic acid in inhibiting platelet aggregation had not been fully clarified. Reported effects of ferulic acid included influence on 5-HT release (Yin et al, 1980 ), TXA2/PGI2 balance (Xu et al, 1984 ), arachidonic acid metabolism (Xu et al, 1990 ), and activation of cAMP and cGMP signaling (Hong et al, 2016 ; Nadal et al, 2016 ). Effects of ferulic acid on cAMP might be the basis of antagonism between ferulic acid and forskolin (DG:MH).…”