Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;40(4):989-998.
doi: 10.1007/s11095-023-03508-x. Epub 2023 Apr 6.

Dissolution Profiles of Poorly Soluble Drug Salts in Bicarbonate Buffer

Aoi Sakamoto  1 , Kiyohiko Sugano  2
Affiliations

Dissolution Profiles of Poorly Soluble Drug Salts in Bicarbonate Buffer

Aoi Sakamoto et al. Pharm Res. 2023 Apr.

Abstract

Purpose: The purpose of the present study was to investigate the effect of buffer species on the dissolution profiles of poorly soluble drug salts, focusing on bicarbonate buffer (BCB).

Methods: Pioglitazone HCl (PIO HCl) and dantrolene sodium (DNT Na) were used as model drugs. Non-sink dissolution tests were performed using phosphate buffer (PB) and BCB (pH 6.5, buffer capacity: 4.4 mM/pH, ionic strength: 0.14 M, with/ without bile micelles). The pH value of BCB was maintained using a floating lid that avoided the loss of CO2. The particles collected at the early stage of dissolution (< 5 min) were analyzed by powder X-ray diffraction, polarized light microscopy, and scanning electron microscopy. A bulk-phase pH shift precipitation test was also performed.

Results: The dissolution of PIO HCl was slower in BCB than in PB, whereas that of DNT Na was faster in BCB than in PB. The same trend was observed in the presence of bile micelles. Free-form precipitation on the surface of salt particles was observed early in their dissolution in both BCB and PB. However, the surface textures in BCB and PB were different. The bulk-phase precipitation of PIO was little affected by buffer species, whereas that of DNT was affected, but oppositely to the dissolution profile.

Conclusion: The dissolution profiles of PIO HCl and DNT Na in BCB were markedly different from those in PB. Free-form precipitation on the particle surface, rather than in the bulk phase, was affected by buffer species in the dissolution test.

Keywords: bicarbonate; biorelevant; disolution; salt; supersaturation.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Zaborenko N, Shi Z, Corredor CC, Smith-Goettler BM, Zhang L, Hermans A, et al. First-principles and empirical approaches to predicting in vitro dissolution for pharmaceutical formulation and process development and for product release testing. AAPS J. 2019;21:1–20. - DOI
    1. Mudie DM, Samiei N, Marshall DJ, Amidon GE, Bergström CAS. Selection of in vivo predictive dissolution media using drug substance and physiological properties. AAPS J. 2020;22:34. - DOI - PubMed
    1. Lennernäs H, Lindahl A, van Peer A, Ollier C, Flanagan T, Lionberger R, et al. In vivo predictive dissolution (IPD) and biopharmaceutical modeling and simulation: future use of modern approaches and methodologies in a regulatory context. Mol Pharm. 2017;14:1307–14. - DOI - PubMed
    1. McAllister M. Dynamic dissolution: a step closer to predictive dissolution testing? Mol Pharm. 2010;7:1374–87. - DOI - PubMed
    1. Fadda HM, Merchant HA, Arafat BT, Basit AW. Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems. Int J Pharm. 2009;382:56–60. - DOI - PubMed

LinkOut - more resources