Gautschi, Nicolas
Lade...
E-Mail-Adresse
Geburtsdatum
Projekt
Organisationseinheiten
Berufsbeschreibung
Nachname
Gautschi
Vorname
Nicolas
Name
Gautschi, Nicolas
2 Ergebnisse
Suchergebnisse
Gerade angezeigt 1 - 2 von 2
- PublikationMolecular insights into the formation of drug-monoacyl phosphatidylcholine solid dispersions for oral delivery(Elsevier, 2016) Gautschi, Nicolas; van Hoogevest, Peter; Kuentz, Martin [in: European Journal of Pharmaceutical Sciences]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.01A - Beitrag in wissenschaftlicher Zeitschrift
- PublikationRapid determination of drug solubilization versus supersaturation in natural and digested lipids(Elsevier, 2016) Gautschi, Nicolas; Bergstroem, Christel; Kuentz, Martin [in: International Journal of Pharmaceutics]Lipid-based formulations (LBFs) represent one of the successful formulation approaches that enable oral delivery of poorly water-sol. drugs. This work presents a simple equil. approach based on soly. in lipids and their corresponding digestion media to est. a max. drug supersatn. ratio (SRmax). This value of drug concn. normalized by the soly. in the aq. digestion phase indicates the propensity for drug pptn. A set of 16 structurally diverse drugs was first measured for their soly. in tricaprin and tricaprylin and results were compared to an empirical model based on mol. predictors. In the next step, digestion media were either prepd. by in vitro lipolysis or by assembling a compn. to mimic the endpoint of digestion. It was found that drug soly. in the pure lipids mainly was related to the m.p. in that increased values resulted in reduced soly. The soly. values measured in the lipolysis media correlated well with those obtained from assembled digestion media. Interestingly, the solubilization upon digestion was typically higher when using tricaprin than tricaprylin in spite of that the latter oil (as pure excipient) generally was a more potent solvent. This work suggests that a simplified digestion screen can be used to facilitate evaluation of formulations during early development. Estn. of SRmax provides an early risk assessment of drug pptn. for LBFs. The method is easily scaled down to the microtiter plate format and can be used for selecting candidate formulations that merit further evaluation in more complex and dynamic in vitro tests.01A - Beitrag in wissenschaftlicher Zeitschrift