Influence of the introduction of a solubility enhancer on the formulation of lipidic nanoparticles with improved drug loading rates

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 75; no. 2; pp. 117 - 127
• Main Authors: Malzert-Fréon, A., Saint-Lorant, G., Hennequin, D., Gauduchon, P., Poulain, L., Rault, S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-06-2010; Elsevier
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Biological and medical sciences; Drug Stability; Emulsions; Excipients - chemistry; Galenic pharmacology; General pharmacology; Glycerides; Labrasol; Least-Squares Analysis; Life Sciences; Lipids - chemistry; Medical sciences; Microscopy, Electron, Transmission; Nanoparticles; Organic Chemicals - chemistry; Partial least square; Particle Size; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase inversion; Pyrrolizidine Alkaloids - administration & dosage; Pyrrolizidine Alkaloids - chemistry; Solubility; Temperature; Tripentone; PIZ; Phase inversion; HLD; NP; Tripentone; Partial least square; Nanoparticles; Labrasol; PEG; PDI; o/w; w/o; SAD; PIT; Drug; Pharmaceutical technology; Nanoparticle; Solubility; Phase reversal; Formulation; Microparticle; Physicochemical properties
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.02.003

The objective of the present paper is to develop lipidic nanoparticles (NP) able to encapsulate drugs presenting limited solubility in both water and lipids, with high loading rates, and without using organic solvents. In this goal, a solubility enhancer, a macrogolglyceride (Labrasol®), was incorporated in a formulation process based on a low-energy phase inversion temperature method. From electrical conductivity through the temperature scans, it appears that presence of Labrasol® does not prevent the phase inversion, and it takes part in the microemulsion structuring, probably of bicontinuous type. After screening pseudo-ternary diagrams, the feasibility of NP was established. From results of a partial least square analysis, it appears that these NP present a core–shell structure where Labrasol® is well encapsulated and contributes to the formation of the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light scattering, remains kinetically stable. These NP, smaller than 200
nm, spherical in shape as attested by cryo-transmission electron micrographs, are able to encapsulate a tripentone, a new anticancer agent, with drug loading rates up to 6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without using the slightest organic solvent trace, and making it easily possible dose adjustment.