Formulation and processing of solid self-emulsifying delivery systems (HME S-SEDDS): A single-step manufacturing process via hot-melt extrusion technology through response surface methodology
The objective of the current study is the formulation development and manufacturing of solid self-emulsifying delivery systems (HME S-SEDDS) via a single-step continuous hot-melt extrusion (HME) process. For this study, poorly soluble fenofibrate was selected as a model drug. From the results of pre-formulation studies, Compritol® HD5 ATO, Gelucire® 48/16, and Capmul® GMO-50 were selected as oil, surfactant and co-surfactant respectively for manufacturing of HME S-SEDDS. Neusilin® US2 was selected as a solid carrier. The design of experiments (response surface methodology) was employed to prepare formulations via a continuous HME process. The formulations were evaluated for emulsifying properties, crystallinity, stability, flow properties and drug release characteristics. The prepared HME S-SEDDS showed excellent flow properties, and the resultant emulsions were stable. The globule size of the optimized formulation was 269.6 nm. The DSC and XRD studies revealed the amorphous nature of the formulation and FTIR showed no significant interaction between fenofibrate and excipients. The drug release studies showed significant (p<0.05) improvement in solubility compared to the pure drug (DE15 =45.04 for the optimized formulation), as >90% of drug release was observed within 15 minutes. The stability studies for the optimized formulation were conducted for 3 months at 40°C/75% RH.
Materials
Fenofibrate (API) was donated by Ashland Inc. (Lexington, KY, USA). Compritol ® HD5 ATO (Behenoyl polyoxyl-8 glycerides), Gelucire® 48/16 (Polyoxyl-32 stearate (type 1), Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides), Geleol™ (Glycerol Monostearate 40-55 (Type I)), Labrafil® 2130CS (Lauroyl polyoxyl-6 glycerides) were gift samples from Gattefosse (NJ, USA). Capmul® GMO-50 (Glyceryl Monooleate with di and triglycerides) was a gift sample from Abitec (OH, USA). Kolliphor® 407 was donated by BASF, Neusilin® US2 was donated by Fuji Chemical Industries.
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Venkata Raman Kallakunta, Narendar Dudhipala, Dinesh Nyavanandi, Sandeep Sarabu, Karthik Yadav Janga, Srinivas Ajjarapu, Suresh Bandari, Michael A. Repka, Formulation and processing of solid self-emulsifying delivery systems (HME S-SEDDS): A single-step manufacturing process via hot-melt extrusion technology through response surface methodology, International Journal of Pharmaceutics, 2023, 123055, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.123055.