The influence of self-assembling supramolecular structures on the passive membrane transport of ion-paired molecules

Benaouda, Faiza; Brown, Marc; Shah, Bina; Martin, Gary P.; Jones, Stuart A.

doi:10.1016/j.ijpharm.2012.09.001

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…Permeability study of 5FU cocrystals was carried out using a Franz diffusion cell with a silicone membrane as an alternative nonpolar membrane to human and animal skin, for a duration of 10 h. − The cumulative amount per unit area permeated ( Q n ) of 1 – 3 , with form I of 5FU as a control, is shown in Figure in the form of Q n of 5FU (μg/cm 2 ) vs time (h). The plots indicate that Q n ’s of 5FU/cocrystals increase slowly with time.…”

Section: Resultsmentioning

confidence: 99%

Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization

Dai

Chen

et al. 2016

Crystal Growth & Design

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Pharmaceutical cocrystallization is proposed as a new method to enhance membrane permeability of a BCS class III model drug, 5-fluorouracil (5FU). Three cocrystals of 5FU, 5FU/3-hydroxybenzoic acid (1), 5FU/4-aminobenzoic acid (2) and 5FU/cinnamic acid (3), were successfully synthesized by a slurry method or a liquid-assisted grinding process. Spectroscopic methods, thermal analysis, and X-ray diffraction were used to characterize these new forms. The permeability was studied using a Franz diffusion cell and silicone membrane. All of the cocrystals showed improved membrane permeability compared to free 5FU. The cumulative amount per unit area of permeated 5FU in the first ten hours for 1-3 were increased by 41%, 70% and 83%, and the steady penetrate rate of 1-3 were increased by 38%, 66% and 79% respectively, as compared to pure drug.Structure-permeability correlation study finds a link between intermolecular interactions and molecular packing in cocrystals and their permeability behavior and has important implications for use of cocrystallization approach to improve drugs' permeability in pharmaceutical field.

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Section: Resultsmentioning

confidence: 99%

Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization

Dai

Chen

et al. 2016

Crystal Growth & Design

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“…The sensitivity of infrared spectroscopy in the liquid state is limited by the large solvent signals recorded by the instrument, but previous work has shown that strong diclofenac-vehicle interactions can be detected using this method. 35 This suggests that if HPMC-drug interactions were present, they were relatively weak or localised to a particular area of the system. This conclusion is supported by the fact that a similar PG-water cosolvent mixture has been previously found not to hinder the diffusion of the solubilised diclofenac in the absence of a second solid phase, 20 and suggests that any solution state interactions between the drug and solvent supramolecular structure have a minimal functional effect in the bulk solution.…”

Section: Discussionmentioning

confidence: 99%

In situ self assembly of soft diclofenac loaded microparticles in superstructured fluids

et al. 2013

Self Cite

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This study investigated how the in situ construction and payload delivery from soft diclofenac loaded hydroxypropylmethylcellulose (HPMC) coated microparticles was influenced by the superstructure of the cosolvent in which the particles were suspended. A dual nozzle spray was used to produce microparticles in a propylene glycol (PG)???water mixture and data generated from the structural features of the vehicle, the physical properties of the particles and drug transport from the suspensions were used to characterise the particle???vehicle interactions. Infrared spectroscopy indicated supramolecular structures were formed in the bulk PG???water cosolvent upon mixing, but no solvent structural modification was observed as a consequence of microparticle self-assembly. Forming the microparticles in a premixed cosolvent, i.e., with a preformed superstructure, did not allow the polymer to deposit on the surface of the microparticles. The suspensions that did not contain the HPMC coated microparticles demonstrated a reduced diclofenac transmembrane transport rate (7.9 ?? 0.4 ??g cm???2 h???1) compared to soft HPMC coated particles (27.7 ?? 3.0 ??g cm???2 h???1). The HPMC???diclofenac hydrogen bonding interactions observed in the polymer coated material, the increased availability of the diclofenac in the solution state (drug degree of saturation rose from 3.0 ?? 0.2 to 11.0 ?? 1.2) and the slower microparticle formation kinetics (>1 order of magnitude) supported the conclusion that the cosolvent supramolecular structuring controlled HPMC deposition at the particle interface. Analysis of the solid material recovered from the suspensions suggested that the cosolvent supramolecular structures could be used to modify the diclofenac solid???liquid equilibrium and generate a complex liquid with an unusually high chemical potential. Graphical abstract: In situ self assembly of soft diclofenac loaded microparticles in superstructured fluids botto

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“…The concept of ion pairing has been utilized in drug designs to alter the hydrophilic/hydrophobic balance of drug molecules. [18][19][20][21] Pairing hydrophilic drug molecules with hydrophobic co-ions/peptides can increase the permeability of drug/co-ion pair into cell membranes, [22,23] enhance transdermal penetration depth, [24] or increase the drug solubility. [25] Ionpairing can tailor the pharmacokinetics of drugs to different applications without modifying its chemical structure.…”

Section: Introductionmentioning

confidence: 99%

Reducing Passive Drug Diffusion from Electrophoretic Drug Delivery Devices through Co‐Ion Engineering

et al. 2021

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Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion‐conducting membrane out to the local implanted area. This solvent‐flow‐free “dry” delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co‐ion is presented. By switching acetylcholine's associated co‐ion from chloride to carboxylate co‐ions as well as sulfopropyl acrylate‐based polyanions, steady‐state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices.

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The influence of self-assembling supramolecular structures on the passive membrane transport of ion-paired molecules

Cited by 6 publications

References 34 publications

Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization

Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization

In situ self assembly of soft diclofenac loaded microparticles in superstructured fluids

Reducing Passive Drug Diffusion from Electrophoretic Drug Delivery Devices through Co‐Ion Engineering

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