Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

Ruponen, Marika; Visti, Maiju; Ojarinta, Rami; Laitinen, Riikka

doi:10.1016/j.ejpb.2018.06.007

Cited by 25 publications

(22 citation statements)

References 66 publications

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“…2). The other formulations have been previously confirmed as being amorphous when cryomilled under similar conditions (Laitinen et al, 2014;Ruponen et al, 2018).…”

Section: X-ray Powder Diffractionmentioning

confidence: 73%

“…According to its FTIR-spectrum, GBC-SER CM was observed to form only weak interactions between GBC and SER (Laitinen et al, 2014). Instead, the spectrum of GBC-ARG CM revealed strong molecular interactions and a possible salt formation between the GBC and ARG molecules (Ruponen et al, 2018). Crystalline GBC showed characteristic carbonyl stretching at 1713 cm -1 and 1615 cm -1 (Fig.…”

Section: Fourier-transform Infrared Spectroscopymentioning

confidence: 96%

“…FTIR measurements were conducted to determine the possible molecular interactions between GBC and QRT. The other cryomilled formulations have been characterized previously (Laitinen et al, 2014;Ruponen et al, 2018). According to its FTIR-spectrum, GBC-SER CM was observed to form only weak interactions between GBC and SER (Laitinen et al, 2014).…”

Section: Fourier-transform Infrared Spectroscopymentioning

confidence: 99%

“…A BCS class II drug glibenclamide (GBC) was used as a model drug, for which poor solubility and dissolution are factors limiting its bioavailability. In a recent study, we demonstrated that co-amorphization of GBC with arginine (ARG), serine (SER) and sodium lauryl sulfate (SLS) enhanced the drug's dissolution and permeability through a PAMPA membrane (Ruponen et al, 2018). In that study, co-amorphous GBC-ARG and GBC-ARG-SLS mixtures displayed superior dissolution properties (due to possible salt formation between GBC and ARG) promoting the flux of GBC through the PAMPA membrane.…”

Section: Introductionmentioning

confidence: 97%

“…At present, the permeability of co-amorphous mixtures has been examined using parallel artificial membrane permeability assay (PAMPA) membranes (Mesallati et al, 2017), but this experimental setup did not explore the effect of drug dissolution rate and supersaturation, as fixed concentrations were used in the donor compartment. Recently, side-by-side diffusion chambers separated by a PAMPA layer were demonstrated to be a feasible method for evaluating simultaneously dissolution and permeability of amorphous products (Ruponen et al, 2018). However, further investigation of the effect of co-amorphization on permeability through biological membranes is needed, as the role of active diffusion has remained unexplored.…”

Section: Introductionmentioning

confidence: 99%

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The effect of co-amorphization of glibenclamide on its dissolution properties and permeability through an MDCKII-MDR1 cell layer

Sormunen

Ruponen

Laitinen

2019

International Journal of Pharmaceutics

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Co-amorphous mixtures have been demonstrated to represent a promising approach for enhancing the dissolution of poorly water-soluble drugs. However, little is known of their permeability properties, especially through biological membranes, or about the relationship between their dissolution and permeability. In the present study, co-amorphous glibenclamide (GBC) mixtures with two amino acids, arginine (ARG) and serine (SER), in molar ratios of 1:1 were prepared by cryomilling. Their dissolution and permeability properties were studied in side-by-side diffusion chambers using cell layers containing Madine Darby kidney cells overexpressing P-glycoprotein (Pgp) transporters (MDCKII-MDR1), as Pgp may influence the absorption of GBC. Furthermore, two other compounds, the flavonoid quercetin (QRT) which is a Pgp inhibitor and the surfactant, sodium lauryl sulfate (SLS), were used as excipients to investigate if they improved either passive or active diffusion of GBC. In addition, amorphous QRT and a co-amorphous mixture of GBC and QRT (1:1) were characterized with respect to their solid-state properties and physical stability. It was demonstrated that co-amorphous GBC mixtures exhibited superior dissolution properties over the corresponding physical mixtures and amorphous GBC. Furthermore, the co-amorphous GBC-ARG-SLS mixture exhibited a 9-fold increase in permeating through the MDCKII-MDR1 cell layer as compared to the corresponding physical mixture. There was a correlation between the dissolution and permeability area under curve (AUC) values, evidence that the main mechanism behind the improved permeability of co-amorphous mixtures was their improved dissolution. The simultaneous dissolution/permeation testing with side-by-side diffusion chambers and MDCKII-MDR1 cells proved to be a feasible method for evaluating the dissolution/permeation interplay of amorphous compounds.

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“…2). The other formulations have been previously confirmed as being amorphous when cryomilled under similar conditions (Laitinen et al, 2014;Ruponen et al, 2018).…”

Section: X-ray Powder Diffractionmentioning

confidence: 73%

Section: Fourier-transform Infrared Spectroscopymentioning

confidence: 96%