Identification and characterization of olanzapine degradation products under oxidative stress conditions

Hiriyanna, S. G.; Basavaiah, K.; Goud, Palusa Sanath Kumar; Dhayanithi, Varadaraji; Raju, K. Narasimha; Pati, Hari N.

doi:10.1556/achrom.20.2008.1.7

Cited by 27 publications

(22 citation statements)

References 8 publications

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“…It was also noticed that the significant peaks of pure drug at specific wave number (3239 cm -1 ) was found to be in reduced form, with less sharpness and more broadness as the amount of mannitol was increased in the samples. These findings clearly prove the reduction of crystallinity in the drug molecule present in samples (Ayala et al, 2006;Ayala, 2007;Hiriyanna et al, 2008).…”

Section: Ft-ir Studiessupporting

confidence: 71%

“…Pure OLZ showed characteristic absorptions at 3239 cm -1 (NH and OH stretching), 2929 cm -1 (C-H stretching), 1587 cm -1 (C=C stretching), 1421 cm -1 (C=N stretching) and 1287 cm -1 (C-N stretching) (Ayala et al, 2006;2007;Hiriyanna et al, 2008). The characteristic peaks of pure OLZ were found to be present in the spectra of PM as well as in solid dispersions.…”

Section: Ft-ir Studiesmentioning

confidence: 94%

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Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

Krishnamoorthy¹,

Suchandrasen

Prasad

2012

Braz. J. Pharm. Sci.

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The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.Uniterms: Olanzapine. Mannitol. Solid dispersions.O objetivo do presente trabalho é estudar o comportamento de dissolução da olanzapina a partir de suas dispersões sólidas de manitol. As dispersões sólidas foram preparadas por dispersão por fusão e caracterizadas por estudos de solubilidade de fase, conteúdo de fármaco e dissolução in vitro. As melhores dispersões quanto à liberação foram selecionadas a partir dos dados de liberação, parâmetros de dissolução e perfis de liberação. Técnicas de caracterização de estado sólido como espectroscopia no infravermelho pela transformada de Fourier (FTIR), difratometria de raios X, calorimetria de varredura diferencial, infravermelho próximo e espectroscopia Raman foram utilizadas para caracterizar os fármacos a partir das dispersões selecionadas. As dispersões foram, também, avaliadas pelos estudos de capacidade de umedecimento e permeação. Os resultados dos estudos de solubilidade de fase e os parâmetros termodinâmicos indicaram a espontaneidade e o efeito de solubilização do transportador. Os resultados dos estudos de liberação mostraram maior aperfeiçoamento da liberação do fármaco das dispersões sólidas, comparativamente à do fármaco puro, e descobriu-se que a liberação aumenta com o aumento do conteúdo de transportador. O mecanismo possível para o aumento da taxa de libera...

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Section: Ft-ir Studiessupporting

confidence: 71%

Section: Ft-ir Studiesmentioning

confidence: 94%

Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

Krishnamoorthy¹,

Suchandrasen

Prasad

2012

Braz. J. Pharm. Sci.

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“…Pure OL showed characteristic absorption bands at 3217 cm À1 (NH stretching), 2929, 2836, and 2791 cm À1 (C-H stretching), 1586 cm À1 (C ¼ C stretching), 1461 cm À1 (C ¼ N stretching), and 1283 cm À1 C-N stretching. (Ayala et al, 2006;Hiriyanna et al, 2008) The FTIR spectra of ascorbic acid indicated a characteristic peak at 1754 cm À1 which is attributed to the C ¼ O stretching vibration commonly observed for carboxyl groups . The characteristic peaks of pure OL and ascorbic acid were found to be present in the spectra of the physical mixture; however, they were shorter than original components.…”

Section: Fourier Transform Infra-red Analysismentioning

confidence: 99%

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

et al. 2016

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Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm 2 ). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.

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“…In order to investigate the loss of OLZ and formation of a degradant, a Q1 scan and product ion scan for all six m/z of previously described degradation products of OLZ in solid oral formulations [26,27] was carried out daily on sample sets 1-3 (and sub-sets A and B).…”

Section: Loss Of Olz and Identification Of 2-oh-olz As Degradantmentioning

confidence: 99%

“…Two degradation product studies using solid oral formulations of OLZ have been published to date and confirmed six degradation products in OLZ tablets: OLZ-lactam, OLZ-ketolactam, OLZketothiolactam, OLZ-N-oxide, OLZ-keto-oxim and a dimeric compound [26,27]. It is not known if any of these are formed in blood or plasma or whether other products are formed.…”

Section: Introductionmentioning

confidence: 99%

Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

Saar¹,

Gerostamoulos²,

Drummer³

et al. 2012

Forensic Science International

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Identification and characterization of olanzapine degradation products under oxidative stress conditions

Cited by 27 publications

References 8 publications

Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

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