pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug | Health & Environmental Research Online (HERO)

HERO ID

8318717

Reference Type

Journal Article

Title

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

Author(s)

Hamed, R; Awadallah, A; Sunoqrot, S; Tarawneh, O; Nazzal, S; Albaraghthi, T; Al Sayyad, J; Abbas, A; ,

Year

2016

Is Peer Reviewed?

Yes

Journal

AAPS PharmSciTech
ISSN: 1530-9932

Publisher

SPRINGER

Location

NEW YORK

Page Numbers

418-426

Language

English

PMID

26202065

DOI

10.1208/s12249-015-0365-2

Web of Science Id

WOS:000373351900019

URL

http://link.springer.com/10.1208/s12249-015-0365-2
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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.