In-Silico Screening of Lipid-Based Drug Delivery Systems

Purpose
This work proposes an in-silico screening method for identifying promising formulation candidates in complex lipid-based drug delivery systems (LBDDS).

Method
The approach is based on a minimum amount of experimental data for API solubilites in single excipients. Intermolecular interactions between APIs and excipients as well as between different excipients were accounted for by the Perturbed-Chain Statistical Associating Fluid Theory. The approach was applied to the in-silico screening of lipid-based formulations for ten model APIs (fenofibrate, ibuprofen, praziquantel, carbamazepine, cinnarizine, felodipine, naproxen, indomethacin, griseofulvin and glibenclamide) in mixtures of up to three out of nine excipients (tricaprylin, Capmul MCM, caprylic acid, Capryol™ 90, Lauroglycol™ FCC, Kolliphor TPGS, polyethylene glycol, carbitol and ethanol).

Results
For eight out of the ten investigated model APIs, the solubilities in the final formulations could be enhanced by up to 100 times compared to the solubility in pure tricaprylin. Fenofibrate, ibuprofen, praziquantel, carbamazepine are recommended as type I formulations, whereas cinnarizine and felodipine showed a distinctive solubility gain in type II formulations. Increased solubility was found for naproxen and indomethacin in type IIIb and type IV formulations. The solubility of griseofulvin and glibenclamide could be slightly enhanced in type IIIb formulations. The experimental validation agreed very well with the screening results.

Conclusion
The API solubility individually depends on the choice of excipients. The proposed in-silico-screening approach allows formulators to quickly determine most-appropriate types of lipid-based formulations for a given API with low experimental effort.

Download the full article here: In-Silico Screening of Lipid-Based Drug Delivery Systems

or continue reading here: Brinkmann, J., Exner, L., Luebbert, C. et al. In-Silico Screening of Lipid-Based Drug Delivery Systems. Pharm Res 37, 249 (2020). https://doi.org/10.1007/s11095-020-02955-0

Materials
The APIs fenofibrate (FFB), ibuprofen (IBU), indomethacin (IND) and felodipine (FEL) with purity >98% were purchased from TCI (Tokyo, Japan). Cinnarizine (CIN), griseofulvin (GRI), glibenclamide (GLI) were purchased from Alfa Aesar (Karlsruhe, Germany) possessing a purity >97%. Tricaprylin (TG808080) and carbitol were purchased from Sigma Aldrich (Steinheim, Germany) with purity >99%. The glycerides are abbreviated in this work according to [22] (e.g. tricaprylin: TG808080, monolaurin: MG80: The first two letters define the type of component (TG = triglyceride, DG = diglyceride and MG = monoglyceride. The capital numbers give the number of carbon atoms in each carbon chain and the subscript denotes the number of unsaturated bonds in each carbon chain.

Caprylic acid (MC80) was obtained from Merck (Darmstadt, Germany) with purity 99%. Capryol 90™ (Capryol 90) was provided by Gattefosse (Saint-Priest Cedex, France). Kolliphor® TPGS (TPGS1000) was provided by BASF (Ludwigshafen, Germany). The surfactants Capryol 90 and TPGS1000 were taken from the same batches as in a recent work [17]. Water was purified by Milli-Q from Merck Millipore (Darmstadt, Germany). Acetonitrile used for the mobile phase in the HPLC was of analytical grade with minimal purity of 99.9% from VWR Chemicals (Darmstadt, Germany). Phosphoric acid was purchased from Sigma Aldrich with purity >99.9%.