Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Mass spectrometric conditions for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide. ESI: electrospray ionization, m/z: mass-to-charge ratio, msec: millisecond.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: LC-MS/MS chromatogram of desmethyl cyclobenzaprine, cyclobenzaprine, cyclobenzaprine-d3 and cyclobenzaprine N-oxide with the respective structural formula.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Liquid Chromatography with Mass Spectroscopy

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Summary of accuracy and precision results for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide (accuracy presented as mean relative error and precision as coefficient of variation, n = 5 per run). CV, coefficient of variation; LLOQ, Lower limit of quantification; QC, quality control.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Control

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Impact of excipient addition in preformulation and formulation development of cyclobenzaprine. A : Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet (mean ± SEM; n ≥ 5). B : Cumulative amount of permeated drug per cm 2 of the respective solution (mean ± SEM; n ≥ 5) adapted from , Int. J. Pharm. 2021. C : Dissolution of the respective sublingual tablet (mean ± SEM; n = 3). D : Correlation of obtained cyclobenzaprine permeability with the added amount of dibasic phosphate (mean ± SEM). R 2 : determination coefficient, SEM: standard error of the mean, *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Formulation, Dissolution, Permeability

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Disintegration of cyclobenzaprine sublingual tablets after addition of 150 µL freshly collected human saliva in dependence on time.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Cytochrome P450 metabolism of cyclobenzaprine. A : Scheme of cyclobenzaprine demethylation by CYP isoenzymes. B : Cumulative amount of permeated desmethyl cyclobenzaprine per cm 2 (mean ± SEM; n = 8). C : Formation of desmethyl cyclobenzaprine by different mucosae and approaches (mean ± SEM; n ≥ 2). D : Formation of desmethyl cyclobenzaprine by human liver microsomes per time (mean ± SEM; n = 3). HLM: human liver microsomes, LLOQ: lower limit of quantification .

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Alteration of cyclobenzaprine sublingual tablets under ambient and stress conditions. ( A ): Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet stored (mean ± SEM; n ≥ 4). ( B ): Dissolution of the respective sublingual tablet stored (mean ± SEM; n = 3). ( C , D ): Visual and microscopic inspection of the primary packaging material and the tablet surface after storage under ambient conditions and stress conditions, respectively. ( E , F ): TOF-MS scan of the rinsed residuals from packaging material after storage under ambient conditions and stress conditions, respectively. m/z: mass-to-charge ratio, SEM: standard error of the mean , *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Dissolution