Molecular insights into the formation of drug-monoacyl phosphatidylcholine solid dispersions for oral delivery
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2016
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
European Journal of Pharmaceutical Sciences
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
Ausgabe / Nummer
Seiten / Dauer
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Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
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Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Phospholipid-based formulations provide a key technol. to formulate poorly water-sol. drugs. A recent interest has been in using phospholipids with a high content of monoacyl phosphatidylcholine (monoacyl PC) due to its ability to form mixed micelles of mono- and di-acylphospholipids upon aq. dispersion. The present work focused on binary drug- monoacyl PC systems (at about equimolar ratio) with respect to screening of solid dispersion feasibility. It was tested whether or not a mol. rule of thumb can predict the desirable absence of drug crystallinity in the products. Subsequently, mol. simulations were performed to gain a better understanding of mol. assocn. between drugs and monoacyl PC. Finally, the glass-forming ability (GFA) of pure drugs was considered with respect to solid dispersion formation. All products were obtained from a solvent-evapn. process and subsequent anal. of potential drug crystallinity was measured with X-ray powder diffraction and differential scanning calorimetry. Mol. simulations were making use of a Monte Carlo algorithm and mol. properties relevant for GFA were calcd. As a result, the dataset of 28 drugs confirmed an earlier proposed empirical rule that enthalpy of fusion and logP were important for solid dispersion formation, while some relevance was also evidenced for drug energies of frontal orbitals. Interestingly, the Monte Carlo simulations revealed several likely assocns. between drug and phospholipid rather than a well-defined single complex formation. However, drug-excipient interactions were still pivotal, since GFA of pure drug could not predict solid dispersion formation. These findings led to important mol. insights into binary solid dispersions of drug and monoacyl PC, which can guide formulators in early drug product development.
Schlagwörter
Poorly water-soluble drugs, Phospholipi, Monoacyl phosphatidylcholine, Monte Carlo simulation, Glass formation
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0928-0987
1879-0720
1879-0720
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
GAUTSCHI, Nicolas, Peter VAN HOOGEVEST und Martin KUENTZ, 2016. Molecular insights into the formation of drug-monoacyl phosphatidylcholine solid dispersions for oral delivery. European Journal of Pharmaceutical Sciences. 2016. DOI 10.1016/j.ejps.2016.05.023. Verfügbar unter: http://hdl.handle.net/11654/23691