Towards more accurate solubility measurements with real time monitoring: a carvedilol case study

Csicsák, Dóra; Borbás, Enikő; Kádár, Szabina; Tőzsér, Petra; Bagi, Péter; Pataki, Hajnalka; Sinkó, Bálint; Takács‐Novák, Krisztina; Völgyi, Gergely

doi:10.1039/d1nj01349a

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…Therefore, the XRD pattern was not apparent. CVD Form I was more stable (melting point: 123–126 °C), but Form II (melting point: 114–115 °C) was used in formulations sold on the market [39] . Fig.…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-assisted continuous crystallization of metastable polymorphic pharmaceutical in a slug-flow tubular crystallizer

Liao,

Huang,

Zhou

et al. 2023

Ultrasonics Sonochemistry

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Section: Resultsmentioning

confidence: 99%

Ultrasound-assisted continuous crystallization of metastable polymorphic pharmaceutical in a slug-flow tubular crystallizer

Liao,

Huang,

Zhou

et al. 2023

Ultrasonics Sonochemistry

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“…Real-time monitoring of solid-state during dissolution represents a tool to obtain a more accurate picture of the solution-mediated transition phenomena [ 19 ]; in this respect, the contemporary measurement of the amount of dissolved rifaximin and the appearance of the β form in suspension reported in Figure 5 and Figure 6 clearly evidence the transition mediated by the dissolution. However, the process appears to be not completed, likely due in part to the limit of the experimental set-up, which can detect only solid particles near to the probe, and in part to the complex process of dissolution/reprecipitation in β form.…”

Section: Discussionmentioning

confidence: 99%

Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin

Bianchera

Nebuloni²,

Colombo³

et al. 2022

Pharmaceutics

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Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation.

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“…Knowing the accurate solubility of a drug in the early stages of development is essential for a successful product. There are many factors that can influence this parameter, including but not limited to: pH and degree of ionization, solubilizing agents, temperature, particle size and crystalline structure [ 11 , 12 , 13 ]. To obtain such solubility data, which is important in terms of bioavailability, buffers with a pH that is relevant in the gastrointestinal tract should be applied.…”

Section: Introductionmentioning

confidence: 99%

The Effect of the Particle Size Reduction on the Biorelevant Solubility and Dissolution of Poorly Soluble Drugs with Different Acid-Base Character

et al. 2023

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Particle size reduction is a commonly used process to improve the solubility and the dissolution of drug formulations. The solubility of a drug in the gastrointestinal tract is a crucial parameter, because it can greatly influence the bioavailability. This work provides a comprehensive investigation of the effect of the particle size, pH, biorelevant media and polymers (PVA and PVPK-25) on the solubility and dissolution of drug formulations using three model compounds with different acid-base characteristics (papaverine hydrochloride, furosemide and niflumic acid). It was demonstrated that micronization does not change the equilibrium solubility of a drug, but it results in a faster dissolution. In contrast, nanonization can improve the equilibrium solubility of a drug, but the selection of the appropriate excipient used for nanonization is essential, because out of the two used polymers, only the PVPK-25 had an increasing effect on the solubility. This phenomenon can be explained by the molecular structure of the excipients. Based on laser diffraction measurements, PVPK-25 could also inhibit the aggregation of the particles more effectively than PVA, but none of the polymers could hold the nanonized samples in the submicron range until the end of the measurements.

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Towards more accurate solubility measurements with real time monitoring: a carvedilol case study

Abstract: The aim of this study was to draw attention to the challenges of solubility measurement and to present new techniques and detection methods that provide more accurate results. Therefore we...

Cited by 8 publications

References 27 publications

Ultrasound-assisted continuous crystallization of metastable polymorphic pharmaceutical in a slug-flow tubular crystallizer

Ultrasound-assisted continuous crystallization of metastable polymorphic pharmaceutical in a slug-flow tubular crystallizer

Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin

The Effect of the Particle Size Reduction on the Biorelevant Solubility and Dissolution of Poorly Soluble Drugs with Different Acid-Base Character

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