title: pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug.
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.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan. rania.hamed@zuj.edu.jo.
authors.forename: Rania
authors.initials: R
authors.lastname: Hamed
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Areeg
authors.initials: A
authors.lastname: Awadallah
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Suhair
authors.initials: S
authors.lastname: Sunoqrot
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Ola
authors.initials: O
authors.lastname: Tarawneh
authors.affiliation: College of Health and Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, 71201, USA.
authors.forename: Sami
authors.initials: S
authors.lastname: Nazzal
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Tamadur
authors.initials: T
authors.lastname: AlBaraghthi
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Jihan
authors.initials: J
authors.lastname: Al Sayyad
authors.affiliation: Hikma Pharmaceuticals, P.O. Box 182400, Amman, 11118, Jordan.
authors.forename: Aiman
authors.initials: A
authors.lastname: Abbas
mesh_terms: D001702:Biopharmaceutics / Q000379:methods; D002021:Buffers; D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D009994:Osmolar Concentration; D010539:Permeability; D011412:Propanolamines / Q000737:chemistry*; D012995:Solubility
chemical_list: D002021:Buffers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: buffer species; carvedilol; dissolution; ionic strength; solubility