Dissolution profiles of high-dose salt-form drugs in bicarbonate buffer and phosphate buffer.

Publisher: Elsevier Country of Publication: United States NLM ID: 2985195R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6017 (Electronic) Linking ISSN: 00223549 NLM ISO Abbreviation: J Pharm Sci Subsets: MEDLINE

Publication: 2016- : New York, NY : Elsevier
Original Publication: Easton, Pa., American Pharmaceutical Assn.

Solubility* ; Phosphates*/chemistry ; Salts*/chemistry ; Bicarbonates*/chemistry; Buffers ; Hydrogen-Ion Concentration ; Pharmaceutical Preparations/chemistry

The purpose of the present study was to compare the dissolution profiles of high-dose salt-form drugs in bicarbonate buffer (BCB) and phosphate buffer (PPB) focusing on the pH changes in the bulk phase. The pH titration curves of BCB and PPB (pH 6.5, buffer capacity (β) = 4.4 mmol/L/pH unit) were first theoretically calculated and experimentally validated. For dissolution tests, six drug salts with an acid counterion, one drug salt with a weak base counterion, and one free acid drug were employed (125-800 mg clinical dose). The dose/fluid volume ratio (Dose/FV) was aligned with the clinical condition. In the pH titration study, the pH value decreased below pH 6.0 by adding HCl > 2.8 mmol/L (BCB) or > 1.6 mmol/L (PPB) and increased above pH 7.0 by adding NaOH > 2.0 mmol/L (BCB) or > 2.4 mmol/L (PPB). In the dissolution test, even though the initial pH and β values were the same, the pH value at 4 h was lower in PPB than in BCB in all cases. For the drug salts with an acid counterion, the area under the dissolution curve was 1.2 to 2.6-fold lower in BCB than in PPB. A marked precipitation process was observed in BCB, but less pronounced or absent in PPB. The results of this study suggest the use of BCB and a clinically equivalent Dose/FV may be valuable in predicting the oral absorption of high-dose drug salts.
Competing Interests: Declaration of competing interest The Author(s) declare(s) that they have no conflicts of interest to disclose.
(Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Keywords: Bicarbonate; Dissolution; High dose; Precipitation; Salt; Supersaturation; pH

0 (Buffers)
0 (Phosphates)
0 (Salts)
0 (Bicarbonates)
0 (Pharmaceutical Preparations)

Date Created: 20241101 Date Completed: 20241222 Latest Revision: 20241222

20241223

10.1016/j.xphs.2024.10.025

39486519