Tags

Type your tag names separated by a space and hit enter

Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs.
Pharm Res. 2003 Oct; 20(10):1641-6.PR

Abstract

PURPOSE

The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs.

METHODS

Preparation of the bicarbonate-containing dissolution medium was monitored by use of a commercially available fiberoptic probe to measure the concentration of dissolved CO2(aq). Intrinsic dissolution measurements at 100 rpm, 37 degrees C for indomethacin and dipyridamole were performed using a rotating disk and UV detection at pH 6.8 and 5.0 in a USP dissolution vessel apparatus.

RESULTS

Indomethacin dissolution at pH 6.8 was significantly impacted by the concentration of CO2(g) in the sparging gas. Dipyridamole flux at pH 6.8 was independent of buffer species or buffer concentrations studied. However, dipyridamole dissolution at pH 5 was also a strong function of the concentration of CO2(g) in the sparging gas.

CONCLUSIONS

Stable bicarbonate biorelevant buffers could be established to perform intrinsic dissolution rate determinations for indomethacin and dipyridamole as long a continuous gas sparging of CO2(g) was used. Depending of the pH of the dissolution medium, the intrinsic dissolution rates of both indomethacin and dipyridamole were affected by the bicarbonate concentration. Sparging with CO2(g) to create physiologic buffers has a unique advantage over conventional buffers in that gas sparging serves as a continuous source of bicarbonate buffer species. This advantage was demonstrated by performing dissolution experiments at pH values typically associated with the fed state (pH 5) and applying relatively low CO2(g) pressures, resulting in bicarbonate concentrations less than 0.5 mM. It was demonstrated that CO2(g) sparging at a pH consistent with the fed state created an in-situ bicarbonate buffer at low concentrations, which had a significant impact on the dissolution of a basic drug such as dipyridamole.

Authors+Show Affiliations

McNamara DP
Purdue Pharma L.P., International Research and Development, 444 Saw Mill River Road, Ardsley, New York 10502, USA. daniel.mcnamara@pharma.com
Whitney KM
No affiliation info available
Goss SL
No affiliation info available

MeSH

BicarbonatesBuffersChemical PhenomenaChemistry, PharmaceuticalChemistry, PhysicalHydrogen-Ion ConcentrationIonsPharmaceutical PreparationsSolubilitySolventsTechnology, PharmaceuticalTime Factors

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

14620520

Citation

McNamara, Daniel P., et al. "Use of a Physiologic Bicarbonate Buffer System for Dissolution Characterization of Ionizable Drugs." Pharmaceutical Research, vol. 20, no. 10, 2003, pp. 1641-6.
McNamara DP, Whitney KM, Goss SL. Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs. Pharm Res. 2003;20(10):1641-6.
McNamara, D. P., Whitney, K. M., & Goss, S. L. (2003). Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs. Pharmaceutical Research, 20(10), 1641-6.
McNamara DP, Whitney KM, Goss SL. Use of a Physiologic Bicarbonate Buffer System for Dissolution Characterization of Ionizable Drugs. Pharm Res. 2003;20(10):1641-6. PubMed PMID: 14620520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs. AU - McNamara,Daniel P, AU - Whitney,Katherine M, AU - Goss,Sandra L, PY - 2003/11/19/pubmed PY - 2004/7/15/medline PY - 2003/11/19/entrez SP - 1641 EP - 6 JF - Pharmaceutical research JO - Pharm Res VL - 20 IS - 10 N2 - PURPOSE: The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs. METHODS: Preparation of the bicarbonate-containing dissolution medium was monitored by use of a commercially available fiberoptic probe to measure the concentration of dissolved CO2(aq). Intrinsic dissolution measurements at 100 rpm, 37 degrees C for indomethacin and dipyridamole were performed using a rotating disk and UV detection at pH 6.8 and 5.0 in a USP dissolution vessel apparatus. RESULTS: Indomethacin dissolution at pH 6.8 was significantly impacted by the concentration of CO2(g) in the sparging gas. Dipyridamole flux at pH 6.8 was independent of buffer species or buffer concentrations studied. However, dipyridamole dissolution at pH 5 was also a strong function of the concentration of CO2(g) in the sparging gas. CONCLUSIONS: Stable bicarbonate biorelevant buffers could be established to perform intrinsic dissolution rate determinations for indomethacin and dipyridamole as long a continuous gas sparging of CO2(g) was used. Depending of the pH of the dissolution medium, the intrinsic dissolution rates of both indomethacin and dipyridamole were affected by the bicarbonate concentration. Sparging with CO2(g) to create physiologic buffers has a unique advantage over conventional buffers in that gas sparging serves as a continuous source of bicarbonate buffer species. This advantage was demonstrated by performing dissolution experiments at pH values typically associated with the fed state (pH 5) and applying relatively low CO2(g) pressures, resulting in bicarbonate concentrations less than 0.5 mM. It was demonstrated that CO2(g) sparging at a pH consistent with the fed state created an in-situ bicarbonate buffer at low concentrations, which had a significant impact on the dissolution of a basic drug such as dipyridamole. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/14620520/Use_of_a_physiologic_bicarbonate_buffer_system_for_dissolution_characterization_of_ionizable_drugs_ DB - PRIME DP - Unbound Medicine ER -