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Concentration Profiles of Carvedilol: A Comparison Between In Vitro Transfer Model and Dissolution Testing

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Abstract

Purpose

The study aims to investigate the transfer behavior of the weakly basic BCS class II model drug carvedilol from the stomach to the small intestine and compare the concentration profiles of carvedilol that were determined during the in vitro transfer model and dissolution testing.

Methods

An in vitro transfer model, previously introduced by Kostewicz et al., was used in this study. A donor phase of simulated gastric fluid was used to predissolve Dilatrend® tablet (25 mg carvedilol). Media that simulate and cover the physiological pH and buffer capacity ranges of the intestinal fluid were used as acceptor phases. pH measurements were reported to investigate the effect of addition of donor phase containing predissolved carvedilol on lowering the pH of the acceptor media. The f2 similarity factor was used to compare the concentration profiles of carvedilol determined during the in vitro transfer model.

Results

Carvedilol was completely dissolved in all tested acceptor phases, resulted in no precipitation. The buffering capacity of the acceptor phase plays an important role in determining its pH. A discrepancy was found between the concentrations of carvedilol in all tested acceptor phases obtained using the transfer model and those reported using dissolution apparatus II in corresponding media.

Conclusions

Results showed that dissolution testing using apparatus II might not be sufficient to predict its transfer from the stomach into the small intestine and that the in vitro transfer model may be more effective at mimicking the conditions in the gastrointestinal tract.

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Funding

This project was financially supported by the Deanship of Academic Research and Graduate Studies at Al-Zaytoonah University of Jordan.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan

    Rania Hamed & Areej Kamal

Authors
  1. Rania Hamed
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  2. Areej Kamal
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Corresponding author

Correspondence to Rania Hamed.

Electronic Supplementary Material

Fig. 1S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in acetate buffer. Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 21 kb)

High Resolution image (TIF 29 kb)

Fig. 2S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in blank FaSSIF. Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 23 kb)

High Resolution image (TIF 29 kb)

Fig. 3S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in blank FeSSIF. Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 29 kb)

Fig. 4S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in SIFsp. Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 29 kb)

Fig. 5S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in water. Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 20 kb)

High Resolution image (TIF 28 kb)

Fig. 6S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 6.25 mM (pH 6.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 29 kb)

Fig. 7S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 12.5 mM (pH 6.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 23 kb)

High Resolution image (TIF 29 kb)

Fig. 8S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 25 mM (pH 6.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 23 kb)

High Resolution image (TIF 29 kb)

Fig. 9S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 50 mM (pH 6.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 28 kb)

Fig. 10S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 100 mM (pH 6.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 28 kb)

Fig. 11S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 100 mM (pH 7.2). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 22 kb)

High Resolution image (TIF 28 kb)

Fig. 12S

CTransfer and CDissolution profiles of carvedilol from Dilatrend® tablets in phosphate buffer 100 mM (pH 7.8). Data are represented as the mean ± SD (CTransfer, n = 3 and CDissolution, n = 6) (PNG 20 kb)

High Resolution image (TIF 26 kb)

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Hamed, R., Kamal, A. Concentration Profiles of Carvedilol: A Comparison Between In Vitro Transfer Model and Dissolution Testing. J Pharm Innov 14, 123–131 (2019). https://doi.org/10.1007/s12247-018-9337-x

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  • DOI: https://doi.org/10.1007/s12247-018-9337-x

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