Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin.

J Pharm Sci 2016 Apr 5;105(4):1362-9. Epub 2016 Mar 5.

Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. Electronic address:

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a "worst case" approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release ribavirin formulations containing different excipients and produced by different manufacturing methods been reported in the open literature. So the risk of bioinequivalence caused by these factors appears to be low. Ribavirin is considered a narrow therapeutic index drug, as judged by comparing the minimum effective concentration and minimum toxic concentrations in blood. Although ribavirin would not be eligible for approval via a Biopharmaceutical Classification System-based biowaiver procedure according to today's guidances due to its narrow therapeutic index, the risks of biowaiving should be weighed against the considerable risks associated with studying BE of ribavirin products in healthy subjects.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xphs.2016.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126353PMC
April 2016

Publication Analysis

Top Keywords

ribavirin
10
dosage forms
8
solid oral
8
release solid
8
biopharmaceutical classification
8
forms ribavirin
8
narrow therapeutic
8
oral dosage
8
eligible approval
4
approval biopharmaceutical
4
jejunum hcnt2
4
hcnt2 saturable
4
uptake intestine
4
saturable uptake
4
intestine common
4
ribavirin absorption
4
blood ribavirin
4
compete ribavirin
4
excipients compete
4
classification system-based
4

Similar Publications

Biowaiver monographs for immediate-release solid oral dosage forms: stavudine.

J Pharm Sci 2012 Jan 15;101(1):10-6. Epub 2011 Sep 15.

Brazilian Health Surveillance Agency, Anvisa, Division of Bioequivalence, Brasilia, Brazil.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing stavudine (d4T) are reviewed. According to Biopharmaceutics Classification System (BCS), d4T can be assigned to BCS class I. No problems with BE of IR d4T formulations containing different excipients and produced by different manufacturing methods have been reported and, hence, the risk of bioinequivalence caused by these factors appears to be low. Read More

View Article and Full-Text PDF
January 2012

Biowaiver monographs for immediate release solid oral dosage forms: aciclovir.

J Pharm Sci 2008 Dec;97(12):5061-73

Facultad de Farmacia, Universidad de Valencia, Burjassot 46100, Valencia, Spain.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. Read More

View Article and Full-Text PDF
December 2008

Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen.

J Pharm Sci 2012 Oct 11;101(10):3593-603. Epub 2012 Jul 11.

Sechenov First Moscow State Medical University, Moscow, Russia.

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing ketoprofen are reviewed. Ketoprofen's solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA)/dissolution data were taken into consideration. The available data suggest that according to the current Biopharmaceutics Classification System (BCS) and all current guidances, ketoprofen is a weak acid that would be assigned to BCS Class II. Read More

View Article and Full-Text PDF
October 2012

Biowaiver monographs for immediate release solid oral dosage forms: ethambutol dihydrochloride.

J Pharm Sci 2008 Apr;97(4):1350-60

Institute of Pharmaceutical Technology, J.W. Goethe University, Frankfurt am Main, Germany.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing ethambutol dihydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ethambutol dihydrochloride is a Biopharmaceutics Classification System (BCS) Class III drug with permeability properties approaching the border between BCS Class I and III. BE problems of ethambutol formulations containing different excipients and different dosages forms have not been reported and hence the risk of bioinequivalence caused by excipients is low. Read More

View Article and Full-Text PDF
April 2008