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Development of a discriminating in vitro dissolution method for a poorly soluble NO-donating selective cyclooxygenase-2 inhibitor.
J Pharm Biomed Anal. 2008 May 12; 47(1):16-22.JP

Abstract

A discriminating dissolution method using a USP apparatus 2 dissolution tester was developed for a nitric oxide donating selective COX-2 inhibitor to support phase I and II formulation development, clinical supplies release and stability testing of an immediate release oral tablet. The BCS class II compound showed very low aqueous solubility and required the use of surfactant-containing (sodium lauryl sulfate (SLS)) dissolution medium in order to achieve an appropriate release profile. The dissolution method utilized 900 mL of 2% SLS (w/v). Samples were withdrawn at five specified time-points over 60 min, at a paddle speed of 75 rpm. Analysis of samples was performed using a validated HPLC method. Despite the use of high levels of SLS, the ability to discriminate variations in physical properties such as drug particle size, granule particle size and tablet compression force was demonstrated. In order to confirm the relationship between these physical parameters and the tablet in vivo release profile, oral dosing of the formulations in fasted beagle dogs was performed to determine if the changes observed in the dissolution profiles were biorelevant. The results of the dissolution and corresponding in vivo experiments helped identify the critical processing parameters likely to influence product bioavailability.

Authors+Show Affiliations

Drug Metabolism and Pharmacokinetics, Merck Frosst Center for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada H9H 3L1. robert_papp@merck.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18272312

Citation

Papp, Robert, et al. "Development of a Discriminating in Vitro Dissolution Method for a Poorly Soluble NO-donating Selective Cyclooxygenase-2 Inhibitor." Journal of Pharmaceutical and Biomedical Analysis, vol. 47, no. 1, 2008, pp. 16-22.
Papp R, Luk P, Mullett WM, et al. Development of a discriminating in vitro dissolution method for a poorly soluble NO-donating selective cyclooxygenase-2 inhibitor. J Pharm Biomed Anal. 2008;47(1):16-22.
Papp, R., Luk, P., Mullett, W. M., Kwong, E., Debnath, S., & Thibert, R. (2008). Development of a discriminating in vitro dissolution method for a poorly soluble NO-donating selective cyclooxygenase-2 inhibitor. Journal of Pharmaceutical and Biomedical Analysis, 47(1), 16-22. https://doi.org/10.1016/j.jpba.2007.12.025
Papp R, et al. Development of a Discriminating in Vitro Dissolution Method for a Poorly Soluble NO-donating Selective Cyclooxygenase-2 Inhibitor. J Pharm Biomed Anal. 2008 May 12;47(1):16-22. PubMed PMID: 18272312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a discriminating in vitro dissolution method for a poorly soluble NO-donating selective cyclooxygenase-2 inhibitor. AU - Papp,Robert, AU - Luk,Pauline, AU - Mullett,Wayne M, AU - Kwong,Elizabeth, AU - Debnath,Smita, AU - Thibert,Roch, Y1 - 2007/12/23/ PY - 2007/09/28/received PY - 2007/11/26/revised PY - 2007/12/06/accepted PY - 2008/2/15/pubmed PY - 2008/12/17/medline PY - 2008/2/15/entrez SP - 16 EP - 22 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 47 IS - 1 N2 - A discriminating dissolution method using a USP apparatus 2 dissolution tester was developed for a nitric oxide donating selective COX-2 inhibitor to support phase I and II formulation development, clinical supplies release and stability testing of an immediate release oral tablet. The BCS class II compound showed very low aqueous solubility and required the use of surfactant-containing (sodium lauryl sulfate (SLS)) dissolution medium in order to achieve an appropriate release profile. The dissolution method utilized 900 mL of 2% SLS (w/v). Samples were withdrawn at five specified time-points over 60 min, at a paddle speed of 75 rpm. Analysis of samples was performed using a validated HPLC method. Despite the use of high levels of SLS, the ability to discriminate variations in physical properties such as drug particle size, granule particle size and tablet compression force was demonstrated. In order to confirm the relationship between these physical parameters and the tablet in vivo release profile, oral dosing of the formulations in fasted beagle dogs was performed to determine if the changes observed in the dissolution profiles were biorelevant. The results of the dissolution and corresponding in vivo experiments helped identify the critical processing parameters likely to influence product bioavailability. SN - 0731-7085 UR - https://www.unboundmedicine.com/medline/citation/18272312/Development_of_a_discriminating_in_vitro_dissolution_method_for_a_poorly_soluble_NO_donating_selective_cyclooxygenase_2_inhibitor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(07)00764-9 DB - PRIME DP - Unbound Medicine ER -