In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

Franek, Frans; Jarlfors, A.; Larsen, Frank; Holm, Per; Steffansen, Bente

doi:10.1016/j.ejps.2015.06.012

Cited by 11 publications

(13 citation statements)

References 38 publications

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“…According to the semi-mechanistic model conducted by Franek et al (2015), our results of a more delayed drug release are more preferable compared to faster release preparations. This is mainly due to the suggestion that Desvenlafaxine absorption from Immediate Release Formulation (IRF) is rate-limited by permeability, whereas Desvenlafaxine absorption from Extended Release Formulations (ERFs) is likely rate-limited by dissolution due to the formulation.…”

Section: Resultsmentioning

confidence: 93%

“…DSV, being a weak basic drug (Völgyi et al, 2010), dissolves easily in gastric fluids and is highly absorbed after oral administration, which exaggerates its side effects. Indeed, this highlights the need to prepare extended release of DSV tablets to increase the compliance of patients suffering from depressive disorder and decrease side effects compared to the immediate release formulation (Franek et al, 2015, McLaughlin et al, 2007). Being a relatively new drug (Hussar and Campoli, 2008), few trails have been made to develop sustained release preparation of DSV.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Samy

Elnoby

El‐Gowelli

et al. 2017

Saudi Pharmaceutical Journal

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Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and DSV release. The release kinetics were calculated to determine the drug release mechanism. DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (P) were performed using everted sac technique. Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7). A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Samy

Elnoby

El‐Gowelli

et al. 2017

Saudi Pharmaceutical Journal

View full text Add to dashboard Cite

show abstract

“…This equation is derived based on the assumption that the particle radius is significantly larger than its boundary layer thickness. However, when the boundary layer thickness is in the same range as the radius of the particle ( r ≈ h eff , generally when the particle radius is less than 30 µm [176]), the conservation of species equation and Fick’s law of diffusion in spherical coordinates can be used to derive a dissolution expression [177, 178]:

\frac{d C_{aq}}{d t} = - \frac{4 π r^{2} N D_{eff}}{V} false(\frac{1}{r} + \frac{1}{h_{italiceff}} false) false(C_{aq}^{eq} - C_{aq} false)

where N is the number of undissolved particles, and r is the particle radius (Figure 7). To account for non-sphericity of the dissolving particle, a shape factor S is incorporated as a multiplier of the dissolution rate equations [166, 179].…”

Section: Value Of Mathematical Modeling and Existing Modeling Apprmentioning

confidence: 99%

Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement

Rezhdo

Speciner

Carrier

2016

Journal of Controlled Release

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The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented.

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“…An early understanding of the physicochemical parameters describing the drug molecule, the mechanism of absorption (passive or carrier mediated) and where in the gastrointestinal tract the absorption takes place, enables efficient optimisation in drug design. The site of absorption, in terms of the longitudinal absorption profile of a new drug in the intestine, is a critical factor in developing either modified release formulations which direct the dose to specific regions in the intestine or for sustained release formulations which may require colonic absorption 2, 13, 14 .…”

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis

Nilsson

Peric

Strimfors

et al. 2017

Sci Rep

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Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

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In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

Cited by 11 publications

References 38 publications

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis

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