A dynamic in vitro permeation study on solid mono- and diacyl-phospholipid dispersions of celecoxib

Jacobsen, Ann-Christin; Elvang, Philipp A.; Bauer‐Brandl, Annette; Brandl, Martin

doi:10.1016/j.ejps.2018.11.003

Cited by 24 publications

(19 citation statements)

References 23 publications

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“…In a previous dissolution/permeation study on solid phospholipid dispersions of celecoxib, a similar effect was observed where the presence of FaSSIF promoted the permeation of freeze-dried celecoxib [27]. Upon freeze-drying, the crystalline tadalafil was amorphized as shown in the XRPD analysis (see Section 3.1).…”

Section: Resultssupporting

confidence: 62%

High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

et al. 2019

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Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeation employing a two-compartment 96-well plate. Freeze-drying from hydro-alcoholic solutions was used to prepare amorphous formulations. The screening approach was tested on amorphous and crystalline tadalafil formulations with and without Soluplus®. The workflow consisted of: (1) dispersion of the formulations; (2) incubation within the two-compartment plate, where a dialysis membrane separated donor (dispersed formulation) and acceptor; (3) sampling (donor and acceptor), where donor samples were centrifuged to remove non-dissolved material; and (4) quantification by UHPLC-UV. To identify optimal screening conditions, the following parameters were varied: dispersion medium (buffer/biomimetic media), acceptor medium (buffer/surfactant solutions), and incubation time (1, 3, and 6 h). Surfactants (acceptor) increased tadalafil permeation. Biomimetic medium (donor) enhanced dissolution, but not permeation, except for freeze-dried tadalafil, for which the permeated amount increased. The predictiveness was evaluated by comparing dissolution-/permeation-results with in vivo bioavailability. In general, both dissolution and permeation reflected bioavailability, whereof the latter was a better predictor. High-throughput dissolution/permeation is regarded promising for formulation screening.

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Section: Resultssupporting

confidence: 62%

High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

et al. 2019

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“…Contrary to the previous findings obtained for deformable liposomes,17,21,23 DPGLs exhibited superior drug encapsulation because the presence of monoacyl phosphatidylcholine increased the solubilization of AZI. Namely, monoacyl phospholipid has been proven as a more efficient solubilizer than diacyl phospholipid 37. The slightly lower encapsulation of AZI in DPGL-2 than in DPGL-1 could be attributed to the possible interaction/competition of the monoacyl phospholipid and the negatively charged phospholipid inside the bilayers of DPGL-2 for AZI; however, further studies, such as Fourier transform infrared spectroscopy (FT-IR), are necessary to prove the interactions of liposomal bilayer constituents and the drug.…”

Section: Resultsmentioning

confidence: 99%

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Vanić¹,

Rukavina²,

Manner³

et al. 2019

IJN

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Background Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC 50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

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“…These results are in line with a report of Fong et al (2016), reporting the absence of any correlation of enhanced apparent solubility of celecoxib in a solid phospholipid dispersion and permeability. A further study by this research group (Jacobsen et al, 2019) concluded that only elevated concentrations of molecularly dispersed API could increase the permeability. Comparable results were reported by Ueda et al (2014), where authors measured the impact of crystallization inhibition by bile acids and lipid micelles solutions on permeation of dexamethasone.…”

Section: Mechanisms Of Uptake From Dissolved Asdsmentioning

confidence: 95%

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

2019

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Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.

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A dynamic in vitro permeation study on solid mono- and diacyl-phospholipid dispersions of celecoxib

Cited by 24 publications

References 23 publications

High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

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