Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery.
Lipid nanoparticles have gained increased interest in the field of dermal products because of various advantages such as improved drug absorption and controlled drug release. The main objective was to investigate the influence of drug solubility and type of lipid carrier on the in vitro drug release. Drugs of different solubilities in the release medium PBS pH 7.4 (dexamethasone: 0.1mg/ml and diclofenac sodium: 5.0mg/ml) and three different lipids (in which the drugs had the highest solubility), Gelucire® 50/13 (solid lipid, mp: 50°C), Witepsol® S55 (solid lipid, mp: 33.5-35.5°C) and Capryol® 90 (liquid lipid) were chosen. The lipid nanoparticles were prepared by high shear homogenization. All nanosuspensions were in the nanometer range (up to 400nm) and the drug encapsulation efficiency was between 84% and 95%. The drug release was prolonged over 48h without an initial burst release and was dependent on the lipid carrier. Formulations containing a higher amount of solid Gelucire® 50/13 released the drugs slower due to the high affinity of the drugs to this lipid product. Inclusion of the liquid lipid Capryol® 90 resulted in a less organized lipidic structures (softer particles) and therefore a faster drug release. Despite its higher water solubility, diclofenac was released slower than dexamethasone because of its higher solubility in the lipid carriers. DSC studies indicated a partial miscibility between the solid lipids and a good miscibility between the solid and liquid lipids. Primary studies using total internal reflection fluorescence (TIRF) microscopy indicated that it is possible to detect individual fluorescently labeled dexamethasone (DXM-F) molecules dissolved in the liquid lipid Capryol® 90. These studies will allow for the precise determination of the drug distribution within the lipid carrier, and the changes upon drug release. In conclusion, lipid carrier type and drug solubility in the lipid have a large influence on the in vitro drug release from lipid nanoparticles.
College of Pharmacy, Department of Pharmaceutical Technology, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Gaith
G
Zoubari
College of Pharmacy, Department of Pharmaceutical Technology, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Sven
S
Staufenbiel
Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
Pierre
P
Volz
Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
Ulrike
U
Alexiev
College of Pharmacy, Department of Pharmaceutical Technology, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany. Electronic address: roland.bodmeier@fu-berlin.de.
Roland
R
Bodmeier
D000279:Administration, Cutaneous; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry; D004008:Diclofenac / Q000008:administration & dosage; D004058:Diffusion; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005223:Fats / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005223:Fats; D008055:Lipids; D009821:Oils; D011108:Polymers; D011409:Propylene Glycols; D013501:Surface-Active Agents; D014280:Triglycerides; C584816:capryol propylene glycol monocaprylate; C071184:Gelucire 50-13; C009683:witepsol; D004008:Diclofenac; D003907:Dexamethasone
Dexamethasone; Diclofenac; In vitro drug release; Lipid nanoparticles; Microencapsulation; Nanocarrier; Single molecule detection; Total internal reflection fluorescence (TIRF) microscopy