Carvedilol: Solubilization and Cyclodextrin Complexation: A Technical Note

Loftsson, Þorsteinn; Vogensen, Stine B.; Desbos, Cyrielle; Jansook, Phatsawee

doi:10.1208/s12249-008-9055-7

Cited by 83 publications

(49 citation statements)

References 26 publications

(36 reference statements)

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“…Although blank FeSSGF exhibited higher pH values compared to 0.7% HCl, SGFsp, and blank FaSSGF (5.0 vs. 1.5, 1.2, and 1.6, respectively), the dissolution of carvedilol was complete. This might be attributed to the presence of acetate buffer in blank FeSSGF, which forms a water-soluble acetate salt (10). Due to the low pH value of the dissolution media, the influence of ionic strength and buffer capacity was not prominent, indicating the important role of pH in determining the percentage of carvedilol released in acidic media.…”

Section: Dissolution Studiesmentioning

confidence: 99%

“…The high percentage of ionized carvedilol (protonated free base) suggests the formation of salts with the anion of buffer systems, which may affect the solubility product of the weakly basic drug (10,11,29). Therefore, the selection of the anion of the buffer system (buffer species) may be important for the in vitro dissolution studies of carvedilol.…”

Section: Solubility Studiesmentioning

confidence: 99%

“…In addition, the presence of acetate buffer in blank FeSSIF would enhance carvedilol dissolution as has been reported by Loftsson et al (10). Unlike blank FaSSIF, the presence of NaCl and phosphate species resulted in the formation of the less soluble hydrochloride and phosphate carvedilol salts, thus reducing the rate of carvedilol dissolution in blank FaSSIF (10).…”

Section: Dissolution Studiesmentioning

confidence: 99%

“…Stillhart et al, for example, found that 78.2-91.8% of carvedilol precipitates in a crystalline or amorphous form under digestion condition (9). Due to its poor aqueous solubility, carvedilol exhibits very low bioavailability (10,11). The oral absorption of carvedilol was predicted using GastroPlus™ simulation to be~45.9% (6).…”

Section: Introductionmentioning

confidence: 99%

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pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

et al. 2015

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Abstract. The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

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Section: Dissolution Studiesmentioning

confidence: 99%

Section: Solubility Studiesmentioning

confidence: 99%

Section: Dissolution Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

et al. 2015

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“…However, if CAR is well absorbed after oral administration, it is subject to firstpass metabolism in the liver resulting in only about 25% absolute bioavailability. [14] Eudragit E100 has already been used to improve the bioavailability of CAR. Recently, E100 nanoparticles containing CAR were prepared by nanoprecipitation.…”

mentioning

confidence: 99%

Use of supercritical CO₂‐aided and conventional melt extrusion for enhancing the dissolution rate of an active pharmaceutical ingredient

Nagy

Sauceau

Nyúl

et al. 2011

Polymers for Advanced Techs

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Dispersing at the molecular level a drug in a polymer matrix is a major challenge to be addressed by the pharmaceutical industry to enhance its bioavailability or to control its release. Melt extrusion and supercritical CO 2 -aided melt extrusion of solid pharmaceutical formulations were performed to enhance the dissolution rate of carvedilol, taken as a model of poorly soluble drug. The presence of the drug improved the processability of the polyacrylate matrix (Eudragit E) through its plasticizing effect. The supercritical method was found gentle compared with melt extrusion owing to the shorter residence time and lower processing temperature and melt viscosity. No traces of decomposition of the drug could be detected after the supercritical extrusion process based on capillary electrophoresis results. This extrusion process resulted in effective homogenization of the components and amorphization of the drug according to Raman mapping, Fourier transform infrared spectrometry, X-ray diffraction, and polarized light microscopy. The kinetics of dissolution can be dramatically improved. C

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Modification of Cyclodextrin for Improvement of Complexation and Formulation Properties

Dash¹,

Konkimalla²

2015

Handbook of Polymers for Pharmaceutical Technologies

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Carvedilol: Solubilization and Cyclodextrin Complexation: A Technical Note

Cited by 83 publications

References 26 publications

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

Use of supercritical CO₂‐aided and conventional melt extrusion for enhancing the dissolution rate of an active pharmaceutical ingredient

Modification of Cyclodextrin for Improvement of Complexation and Formulation Properties

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Carvedilol: Solubilization and Cyclodextrin Complexation: A Technical Note

Cited by 83 publications

References 26 publications

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

Use of supercritical CO2‐aided and conventional melt extrusion for enhancing the dissolution rate of an active pharmaceutical ingredient

Modification of Cyclodextrin for Improvement of Complexation and Formulation Properties

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Product

Resources

About

Use of supercritical CO₂‐aided and conventional melt extrusion for enhancing the dissolution rate of an active pharmaceutical ingredient