Biowaiver monographs for immediate release solid oral dosage forms: Lamivudine

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 lamivudine as the only active pharmaceutical ingredient were reviewed. The solubility and permeability data of lamivudine as...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2011-06, Vol.100 (6), p.2054-2063
Main Authors: Strauch, S., Jantratid, E., Dressman, J. B., Junginger, H. E., Kopp, S., Midha, K. K., Shah, V. P., Stavchansky, S., Barends, D. M.
Format: Article
Language:English
Subjects:
absorption
Administration, Oral
Animals
bioavailability
bioequivalence
Biological and medical sciences
Biological Availability
biopharmaceutics classification system (BCS)
biowaiver
Chemical Phenomena
Excipients
General pharmacology
Humans
lamivudine
Lamivudine - administration & dosage
Lamivudine - chemistry
Lamivudine - pharmacokinetics
Lamivudine - toxicity
Medical sciences
permeability
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Solubility
Therapeutic Equivalency
Tissue Distribution
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Summary: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 lamivudine as the only active pharmaceutical ingredient were reviewed. The solubility and permeability data of lamivudine as well as its therapeutic index, its pharmacokinetic properties, data indicating excipient interactions, and reported BE/bioavailability (BA) studies were taken into consideration. Lamivudine is highly soluble, but its permeability characteristics are not well‐defined. Reported BA values in adults ranged from 82% to 88%. Therefore, lamivudine is assigned to the biopharmaceutics classification system (BCS) class III, noting that its permeability characteristics are near the border of BCS class I. Lamivudine is not a narrow therapeutic index drug. Provided that (a) the test product contains only excipients present in lamivudine IR solid oral drug products approved in the International Conference on Harmonization or associated countries in usual amounts and (b) the test product as well as the comparator product fulfills the BCS dissolution criteria for very rapidly dissolving; a biowaiver can be recommended for new lamivudine multisource IR products and major post‐approval changes of marketed drug products. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2054–2063, 2011
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.22449