Solid-state characterization and dissolution properties of Fluvastatin sodium salt hydrates

Borgmann, S. H. M.; Bernardi, Luana; Rauber, Gabriela Schneider; Oliveira, Paulo Renato de; Campos, Carlos Eduardo Maduro de; Monti, Gustavo A.; Cuffini, Silvia Lucía; Cardoso, Simone Gonçalves

doi:10.3109/10837450.2012.727000

Cited by 4 publications

(9 citation statements)

References 19 publications

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“…In the case of FLV, a first thermal event is observed at 78.5 °C and corresponds to the release of a water molecule of hydration, concerning the data provided by the TGA. In contrast, 215.3 °C corresponds to the melting temperature (T m ) [ 2 ]. PGZ·HCl shows a DSC thermogram with a single event corresponding to the melting temperature of 197.8 °C [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…As can be seen in Figure 4 , the 13 C SSNMR spectra of PGZ∙HCl, FLV and the solid-form PGZ-FLV (EtOH) are found. Notably, in the case of the FLV spectrum, the signals at 158.1 and 162.5 ppm are due to a splitting of C4’ due to a scalar spin–spin C4’-F coupling of 267 Hz [ 2 ]. On the other hand, in the solid-form PGZ-FLV (EtOH) spectrum, only the most important 13 C atoms that participate in relevant molecular interactions are indicated.…”

Section: Resultsmentioning

confidence: 99%

“…Fluvastatin sodium (FLV) belongs to the family of statins, drugs specialized in lowering cholesterol [ 1 , 2 , 3 ] ( Scheme 1 ). Statins inhibit HMG-CoA reductase, implying a reduction in cholesterol synthesis in the blood [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this sense, combining statins with TZD may benefit treating dyslipidemic diabetic individuals [ 4 , 5 ]. FLV was approved by the Food and Drug Administration (FDA) in 1998 and was patented in 1994 as Lescol®, which expired in 2011 [ 2 ]. Lescol® was presented to the market as immediate release (capsule) or sustained release (8 h 80 mg matrix tablet, Lescol® XL) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…They evaluated different crystalline forms: FLV raw material (RM), FLV USP (reference substance), and FLV crystallized in multiple solvents, ethanol, and acetonitrile. In general, FLV (RM) presented the best dissolution profile, and the authors comment that these IDR values may depend on the polymorphism and morphology of FLV [ 2 ]. On the other hand, there is a discrepancy in the literature in determining whether FLV has solubility problems.…”

Section: Introductionmentioning

confidence: 99%

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Diversity of Solid Forms Promoted by Ball Milling: Characterization and Intrinsic Dissolution Studies of Pioglitazone Hydrochloride and Fluvastatin Sodium Drug–Drug Systems

Villeda-Villegas,

Páez-Franco,

Coyote-Dotor

et al. 2023

Pharmaceuticals

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Coamorphous salt in a 1:1 ratio prepared by ball milling from Fluvastatin sodium (FLV) and Pioglitazone hydrochloride (PGZ·HCl) can be selectively formed by neat grinding (NG). Furthermore, the salt–cocrystal continuum was preferably formed by employing liquid-assisted grinding (LAG) using ethanol (EtOH). Attempts to prepare the coamorphous salt starting from the salt–cocrystal continuum by NG were unsuccessful. Interestingly, through ball milling by NG or LAG, a great diversity of solid forms (PGZ·HCl-FLV 1:1) could be accessed: NG and hexane (coamorphous); ethyl acetate (physical mixture); EtOH (salt–cocrystal continuum); and water (which presents two Tg, indicating immiscibility of the components). An exploration was performed at different drug-to-drug ratios by NG. By differential scanning calorimetry (DSC), the presence of two endothermic events was observed in this screening: incongruous melting point (solidus) and excess of one of the components (liquidus), except in the 1:1 solid form. From these results, eutectic behavior was observed. Through the construction of a binary phase diagram, it was determined that the 1:1 molar ratio gives rise to the formation of the most stable coamorphous composition. Dissolution profile studies of these solid forms were carried out, specifically on pure FLV and the solid forms of PGZ⋅HCl-FLV (1:2; 1:4; and 1:6), together with the coamorphous 1:1 salt. By itself, pure FLV presented the highest Kint (13.6270 ± 0.8127 mg/cm2⋅min). On the other hand, the coamorphous 1:1 showed a very low Kint (0.0220 ± 0.0014 mg/cm2·min), indicating very fast recrystallization by the FLV, which avoids observing a sudden release of this drug in the solution. This same behavior was observed in the eutectic composition 1:2. In the other solid forms, the value of Kint increases along with the %w of FLV. From the mechanochemical point of view, ball milling by NG or LAG became an important synthetic tool since it allows obtaining a great variety of solid forms to explore the solid-state reactivity of the drug–drug solid-form PGZ HCl-FLV.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%