Sehic, Selma. Investigation of variability of primary materials on the intrinsic dissolution behavior of carbamazepine. 2008, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_8393
CBZ anhydrous samples showed different intrinsic dissolution behavior. Moreover
examined compacts within one sample have shown high standard deviation. Intrinsic
dissolution parameters were determined with scope to calculate the transition point of
anhydrous to dihydrate conversion for each sample, which was found to vary among the
CBZs obtained from different sources between 15 and 25 minutes.
Carbamazepine dihydrate samples were crystallized from anhydrous samples in order
to be tested on intrinsic dissolution behavior and were characterized by XRPD and DSC
to confirm complete dihydrate formation. It was found that all previously detected
variations between the different samples were significantly reduced, and all nine
samples had constant characteristics. When dihydrate samples were investigated on
intrinsic dissolution behavior, the results showed that deviation within one group of
samples were reduced and the variations between dihydrates prepared from anhydrous
CBZ from different sources did not exist anymore.
Considering that excipients can influence phase transformation of CBZ anhydrous to its
dihydrate form, binary mixtures of CBZ (from different sources) and Fast Flo® lactose
were investigated in this study. Mixtures with different ratios of drug and excipient were
compacted to the same porosity, and disintegration time and intrinsic dissolution
behavior of the produced compacts were studied. The results showed that the selected
excipient had no influence on the anhydrate dihydrate conversion.
As a final step in this study, it was proposed to examine if the results obtained for the
transition point of anhydrous form to dihydrate can be used to predict the dissolution
behavior of CBZ in model formulation. For this purpose, formulations of CBZ were
prepared by direct compaction process using different CBZs and Ludipress®, which
were subsequently analyzed for disintegration time and dissolution. It turned out that the
amount of CBZ dissolved after 15 minutes showed the same order (CBZ B > CBZ A >
CBZ P) being identical to the time event of the transition point determined by intrinsic
dissolution test, meaning CBZ B had the earliest and CBZ P the latest transition point.
Therefore, the intrinsic dissolution test turned out to be a valuable and simple
monitoring tool for characterization of CBZ raw materials, to detect the variability of
primary material, to be employed for the determination of the transition point and to be
used for estimation of CBZ dissolution behavior.
|Committee Members:||Betz, Gabriele and Hoogevest, Peter van|
|Faculties and Departments:||05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||156|
|Last Modified:||30 Jun 2016 10:41|
|Deposited On:||13 Feb 2009 16:37|
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