Polymeric solid dispersion Vs co-amorphous technology: A critical comparison

Vullendula, Sai Krishna Anand; Nair, Athira R; Yarlagadda, Dani Lakshman; Sree, K. Sowjanya; Bhat, Krishnamurthy; Dengale, Swapnil J.

doi:10.1016/j.jddst.2022.103980

Cited by 8 publications

(3 citation statements)

References 141 publications

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“…Although these scenarios are proposed for solid dispersion polymer systems, scenario (C) explains what is happening in our system. It must not be forgotten that coamorphous mixtures fall within the families of solid dispersions [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

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%

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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“…Dissolution plays a crucial role in formulation development, acting as the rate-limiting step for bioavailability [39]. The dissolution profiles of pure lutein, the lutein-sucralose physical mixture, and the lutein-sucralose co-amorphous mixture were determined, and the results are presented in Figure 6.…”

Section: Dissolution Testmentioning

confidence: 99%

Preparation and Characterization of Lutein Co-Amorphous Formulation with Enhanced Solubility and Dissolution

Song,

Luo,

Zhao

et al. 2024

Foods

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Lutein is an oxygenated fat-soluble carotenoid and a functional compound with proven health benefits for the human body. Nevertheless, the poor water solubility and low oral bioavailability of lutein greatly limit its application. To address this, we developed an effective approach to enhance the water solubility of lutein through co-amorphous formulation. Specifically, the lutein-sucralose co-amorphous mixture was prepared at a molar ratio of 1:1 using ethanol and water as solvents by employing the solvent evaporation method, followed by solid-state characterization and dissolution testing conducted to assess the properties of the formulation. The X-ray diffraction pattern with an amorphous halo and the differential scanning calorimetry thermogram with no sharp melting peaks confirmed the formation of a binary co-amorphous system. Changes in peak shape, position, and intensity observed in the Fourier transform infrared spectroscopy spectrum revealed intermolecular interactions between lutein and sucralose molecules, while molecular dynamics simulations identified interaction sites between their hydroxyl groups. Additionally, dissolution testing demonstrated better dissolution performance of lutein in the co-amorphous form compared to pure lutein and physical mixture counterparts. Our findings present a novel strategy for improving the water solubility of lutein to make better use of it.

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“…The generation of amorphous solid dispersions is a modern approach to the creation of a composite that solves the problem of solubilization and its maintenance in an aqueous medium since the solubility of crystalline API can be increased by converting it into an amorphous form, which has a disordered arrangement of molecules over long distances and higher free energy along compared with its crystalline counterpart [10]. However, the excess free energy of the amorphous API can promote its recrystallization, thereby nullifying the advantages of the amorphous form [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability

Markeev

Blynskaya

Tishkov

et al. 2023

IJMS

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This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus® was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus®, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.

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Polymeric solid dispersion Vs co-amorphous technology: A critical comparison

Cited by 8 publications

References 141 publications

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

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

Preparation and Characterization of Lutein Co-Amorphous Formulation with Enhanced Solubility and Dissolution

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability

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