Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets

Monajjemzadeh, Farnaz, Hassanzadeh, Davoud, Valizadeh, Hadi, Siahi-Shadbad, Mohammad R., Mojarrad, Javid Shahbazi, Robertson, Thomas A. and Roberts, Michael S. (2009) Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets. European Journal of Pharmaceutics and Biopharmaceutics, 73 3: 404-413. doi:10.1016/j.ejpb.2009.06.012


Author Monajjemzadeh, Farnaz
Hassanzadeh, Davoud
Valizadeh, Hadi
Siahi-Shadbad, Mohammad R.
Mojarrad, Javid Shahbazi
Robertson, Thomas A.
Roberts, Michael S.
Title Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets
Journal name European Journal of Pharmaceutics and Biopharmaceutics   Check publisher's open access policy
ISSN 0939-6411
1873-3441
Publication date 2009-11-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ejpb.2009.06.012
Open Access Status Not yet assessed
Volume 73
Issue 3
Start page 404
End page 413
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Abstract This study documents drug-excipient incompatibility studies of acyclovir in physical mixtures with lactose and in different tablet brands. Differential scanning calorimetry (DSC) was initially used to assess compatibility of mixtures. The Fourier-transform infrared (FTIR) spectrum was also compared with the spectra of pure drug and excipient. Although DSC results indicated incompatibility with lactose, FTIR spectra were mostly unmodified due to overlapping peaks. Samples of isothermally stressed physical mixture were stored at 95 degrees C for 24 h. The residual drug was monitored using a validated high-performance liquid chromatography (HPLC) assay and data fitting to solid-state kinetic models was performed. The drug loss kinetics followed a diffusion model. The aqueous mixture of drug and excipient was heated in order to prepare an adduct mixture. HPLC analysis revealed one extra peak that was fractionated and subsequently injected into the liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system. The MRM (Multiple Reaction Monitoring) chromatograms characterized the peak with molecular mass corresponding to an acyclovir-lactose Maillard reaction product. The presence of lactose in commercial tablets was checked using a new TLC method. Overall, the incompatibility of acyclovir with lactose was successfully evaluated using a combinadon of thermal methods and LC-MS/MS. I (C) 2009 Published by Elsevier B.V.
Formatted abstract
This study documents drug–excipient incompatibility studies of acyclovir in physical mixtures with lactose and in different tablet brands. Differential scanning calorimetry (DSC) was initially used to assess compatibility of mixtures. The Fourier-transform infrared (FTIR) spectrum was also compared with the spectra of pure drug and excipient. Although DSC results indicated incompatibility with lactose, FTIR spectra were mostly unmodified due to overlapping peaks. Samples of isothermally stressed physical mixture were stored at 95 °C for 24 h. The residual drug was monitored using a validated high-performance liquid chromatography (HPLC) assay and data fitting to solid-state kinetic models was performed. The drug loss kinetics followed a diffusion model. The aqueous mixture of drug and excipient was heated in order to prepare an adduct mixture. HPLC analysis revealed one extra peak that was fractionated and subsequently injected into the liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) system. The MRM (Multiple Reaction Monitoring) chromatograms characterized the peak with molecular mass corresponding to an acyclovir–lactose Maillard reaction product. The presence of lactose in commercial tablets was checked using a new TLC method. Overall, the incompatibility of acyclovir with lactose was successfully evaluated using a combination of thermal methods and LC–MS/MS.
Keyword Acyclovir
Solid state
Lactose
Incompatibility
HPLC
FTIR
DSC
LC-MS/MS
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
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