(M1030-09-52) Development of a Self-Emulsifying Drug Delivery System (SEDDS) of Fenofibrate Using ZoomLab^TM

Purpose: Traditional pre-formulation studies to develop an optimized dosage form are typically based on a trial-and-error approach. This approach is not only cumbersome, but also takes several months to years, and a considerable amount of research capital investment. Newer approaches like Quality by Design (QbD) enabled formulation development has somewhat expedited the process, but are still hindered by multiple trials, and inability to incorporate excipient selection for the most effective dosage form. With advancements in science and technology, it is now possible to develop an optimized formulation based on the properties of the active pharmaceutical ingredient (API). ZoomLab™ is one such advanced formulation algorithm-based platform, which has the capability to predict an optimized dosage form design based on drugs’ physicochemical properties, route of administration, release profile, and compatibility with formulation excipients. This project aims to investigate the utility and robustness of the software in oral drug product design, using a model drug Fenofibrate, a BCS Class-II drug, and an anti-hypertriglyceridemia agent.

Methods: ZoomLab™ (version 4.0) (a trademark of BASF SE) was used to develop a dosage form containing Fenofibrate (120 mg dose). The input parameters related to API and dosage form such as dosage form class, administration route, dosage form, release kinetics, category of dosage form, dose of active ingredient, preferred tablet weight, tensile strength of tablets, melting point, glass transition temperature, etc., were added. Based on the input information, the software scans the physicochemical properties against Lipinski’s “Rule of Five” and categorizes it into appropriate BCS class. Based on drug’s properties, ZoomLab™ predicted self-emulsifying drug delivery system (SEDDS) to be the most appropriate formulation (Feno-SEDDS), and provided Feno-SEDDS carrier formulations, along with excipients, potential drug solubility in these excipients, and detailed instructions. We selected the first formulation (Feno-SEDDS-1) for small-scale lab manufacturing (Fig 1). Briefly, the oil phase consisted of Maisine CC (0.825mL) and refined soybean oil (0.825mL), heated at 50°C. The aqueous phase consisted of Kolliphor RH 40 (1.050mL) and anhydrous ethanol (0.300mL), heated at 50°C. Both phases were mixed on a magnetic stirrer with continuous stirring at 250 rpm at 50°C. Upon homogenous mixing, the API, Fenofibrate (360 mg) was added and was mixed for 2 h to form Feno-SEDDS-1. A calibration curve was constructed using methanol as solvent and at a wavelength of 278nm. Physicochemical characterization of Feno-SEDDS included % drug content, globule size, surface charge, and polydispersity index.

Results: ZoomLab^TM provided 7 optimized SEDDS formulations encapsulating fenofibrate, out of which first formulation (Feno-SEDDS-1) was prepared in lab conditions. As can be seen in Fig. 2, the Feno-SEDDS-1 showed an entrapment of 76.76 ± 1.80%, suggesting the good encapsulation ability of the formulation. The globule size and PDI were found to be 48.65 ± 0.85 nm and 0.06 ± 0.01 respectively suggesting homogenous dispersion of globules throughout the formulation. All the observations point toward developing a successful formulation by a single trial following the recommendations from ZoomLab^TM platform. Further characterization studies are ongoing to assess the drug release, stability, permeation across epithelial membranes, and in-vivo bioavailability.

Conclusion: In this study, we demonstrated the feasibility of ZoomLab^TM platform in predicting a SEDDS formulation of fenofibrate, a BCS Class II drug with low solubility and high permeability. Feno-SEDDS-1 formulation was prepared using the formula and method provided by ZoomLab™ version 4.0. Using this software, a stable and optimized formulation of Feno-SEDDS was developed in no time, without any DOE and ternary phase diagrams.

Feno-SEDDS-1 Formulation as Provided by ZoomLabTM

Results and Calibration curve