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Biowaiver monographs for immediate-release solid oral dosage forms: Zidovudine (azidothymidine).

Journal of pharmaceutical sciences (2013-06-12)
Kelen C C Soares, Camila F Rediguieri, Jacqueline Souza, Cristina Helena R Serra, Bertil Abrahamsson, D W Groot, Sabine Kopp, Peter Langguth, James E Polli, Vinod P Shah, Jennifer Dressman
ABSTRACT

Literature data on the properties of zidovudine relevant to waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate-release (IR) solid oral dosage forms containing zidovudine alone or in combination with other active pharmaceutical ingredients (APIs) are reviewed. Solubility, dissolution, and permeability data for zidovudine, along with its dosing schedule, therapeutic index and pharmacokinetic properties, and reports related to BE/bioavailability were all taken into consideration. Data for solubility and permeability suggest that zidovudine belongs to Class I according to the Biopharmaceutics Classification System. Also, zidovudine is not a narrow therapeutic index drug. Although five out of 13 formulations tested in vivo (mostly of unreported composition) failed to show BE, it appears that in vitro studies performed according to biowaiver methods could predict in vivo behavior. Nevertheless, it is highly recommended that if a biowaiver is to be applied, excipient choices be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form (Table 2 of this monograph), in their usual amounts. These conclusions apply to products containing zidovudine as the only API and also to fixed combination products containing zidovudine with respect to the zidovudine component of the formulation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3′-Azido-3′-deoxythymidine, ≥98% (HPLC)
Supelco
Zidovudine, Pharmaceutical Secondary Standard; Certified Reference Material
Zidovudine, European Pharmacopoeia (EP) Reference Standard