In-Silico Screening of Lipid-Based Drug Delivery Systems

Joscha Brinkmann,Lara Exner,Christian Luebbert,Gabriele Sadowski

doi:10.1007/s11095-020-02955-0

Joscha Brinkmann, Lara Exner + Show 2 more

Open Access

https://doi.org/10.1007/s11095-020-02955-0

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Journal: Pharmaceutical research	Publication Date: Nov 23, 2020
Citations: 9	License type: open-access

Affiliation: TU Dortmund University

Abstract

PurposeThis work proposes an in-silico screening method for identifying promising formulation candidates in complex lipid-based drug delivery systems (LBDDS).MethodThe 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).ResultsFor 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.ConclusionThe 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.Graphical abstract

Highlights

IntroductionMany of the newly-developed active pharmaceutical ingredients (APIs) possess an insufficient solubility in water
Many of the newly-developed active pharmaceutical ingredients (APIs) possess an insufficient solubility in water. If they cannot be administered as conventional tablets providing sufficient bioavailability, other formulation strategies must be explored to overcome this limitation. Promising alternatives in this field are lipid-based drug delivery systems (LBDDS), in which the APIs are dissolved in liquid formulations
Since the API is administered in a dissolved state, LBDDS can avoid the slow API-dissolution step in the human body and increase the API bioavailability. [1,2,3,4] In their simplest form, LBDDS comprise the API dissolved in a pure triglyceride (TG)

Summary

Introduction

Many of the newly-developed active pharmaceutical ingredients (APIs) possess an insufficient solubility in water. If they cannot be administered as conventional tablets providing sufficient bioavailability, other formulation strategies must be explored to overcome this limitation. Promising alternatives in this field are lipid-based drug delivery systems (LBDDS), in which the APIs are dissolved in liquid formulations. LBDDS contain complex mixtures of excipients such as glycerides, surfactants or cosolvents to further enhance the API solubility. The API solubility in the liquid excipient (mixture) is a key property for the development of LBDDS. The most-common experimental methods to measure API solubilities are differential scanning calorimetry (DSC) [9, 13, 16], Raman spectroscopy [9, 13], UV-vis [14, 17], and high-performance liquid chromatography (HPLC) [9, 13, 15]

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