Overcoming the Limited Biovailability of Poorly Soluble Drugs by Lipo-Tops®

This poster has been presented at the 15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, which took place in Prague, Czech Republic.

Overcoming the Limited Biovailability of Poorly Soluble Drugs by Lipo-Tops®

Introduction

Poor solubility and permeability of active ingredients poses as the major challenge in both dermal and oral formulation development.

Lipo-Tops® is a stable oil in water nanoemulsion formulated with two natural, sustainable, non-PEGylated emulsifiers IMWITOR® 375 (Glyceryl Citrate/Linoleate/Oleate) and IMWITOR® 600 (Polyglyceryl-3-Polyricinoleate). To evaluate its ability to enhance delivery of lipophilic actives, Lipo-Tops® were examined in a series of comparative experiments, assessing its ability to increase skin penetration of poorly soluble actives after topical application and transepithelial transport across intestinal Caco-2 epithelia after oral ingestion.

Lipo-Tops® – an O/W Nanoemulsion

Unlike thermodynamically stable transparent microemulsions, Lipo-Tops® are milky with homogeneous droplet sizes ranging from 80 to 250 nm (PDI < 0.2). This fact is explained by the different ratio of emulsifier to oil (1:5 for Lipo-Tops® and 5:1 for micro-emulsions). Despite that, they are distinguished by high encapsulation efficiencies of sensitive, poorly soluble ingredients and oils (rates up to 20%), which led to a significant increase in the hydrophilicity of these substances. Lipo-Tops® can be used in liquid and semisolid formulations.

Dermal Application of Lipo-Tops® L-Tocopherol (10%)

Penetration studies with vesicles containing the antioxidant tocopherol were done using porcine skin and the content of vitamin E in the viable skin was determined by ESR [1].

The encapsulation of the lipophilic vitamin E into LipoTops® enabled more than 8-times higher antioxidative power in the viable skin (epidermis) after penetration compared to liposomes. Lipo-Tops® protect vitamin E so that it could not be easily oxidized to tocopherylquinone and remains much longer reactive. BNC (bacterial nanocellulose) fleeces were successfully loaded with 10% Lipo-Tops® Tocopherol which corresponded to an embedding of 1% pure tocopherol. Studies showed that intact vesicles were released from BNC, maintaining particle size distribution. Tocopherol distribution in the skin revealed in the same behaviour with or without BNC [2,3].

Oral Application of Lipo-Tops® Curcumin Extract (1.5%)

Lipo-Tops® and liposomes containing 1.5% curcumin extract were evaluated for metabolic changes during gastrointestinal passage using an in-vitro digestion simulation [4]. Quantitative analysis showed a recovery rate of 92% curcuminoids with Lipo-Tops® compared to 47 % for liposomes after digest simulation. Metabolic changes in the composition of loaded curcuminoids indicated differences in digestive stability [5].

Additionally, the intestinal transepithelial transport capability of cellviable digest media containing curcuminoids, unencapsulated and encapsulated in liposomes and Lipo-Tops® were studied in the Caco-2 cell model [4]. Notable differences were observed in the transport of curcuminoids across the Caco-2 epithelium: Lipo-Tops® resulted in a 60% higher concentration of substances in the basal compartment compared to liposomes. A notable decrease in TEER (transepithelial electrical resistance) together with high curcumin concentration suggested a partial tight junction opening while maintaining cell viability for LipoTops® [5]. Consistent with literature, curcumin extract demonstrated minimal intestinal absorption [6].

Conclusion

Lipo-Tops® represent a stable innovative natural carrier system that enables an efficient encapsulation of poorly soluble active ingredients.

This oil-in-water nanoemulsion demonstrates a higher bioavailability of lipophilic components in deeper skin areas with long lasting effects as well as a significant increase in the intestinal absorption – compared to a phospholipid-based advanced delivery system.

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Source: sopharcos – Drug Delivery, IOI Oleo, Gabriele Blume, Robert Radsziwill, PBP poster: Overcoming the Limited Biovailability of Poorly Soluble Drugs by Lipo-Tops®