(W1030-03-21) Development and In Vitro Evaluation of Eudragit-Coated Hot-Melt Extruded Ketoprofen-Pectin Pellets for Colon Targeting

Purpose: The present study is intended to develop Ketoprofen (KTP) colon-specific pellets using hot-melt extrusion (HME) coupled with a die-surface cutting pelletizer. KTP was chosen as a model drug for this study because of its thermal stability and severe side effects on the upper gastrointestinal tract. Developing a KTP colon-specific drug delivery system can reduce the drug release in the upper gastrointestinal tract to reduce the side effects related to the drug and improve the therapeutic effect by facilitating the maximum drug release in the colon.

Methods: The KTP pellets were prepared by performing extrusion with an 11 mm twin-screw corotating extruder (Process 11™, Thermo Fisher Scientific). The physical mixture of drug and polymers (high methoxy pectin and hydroxypropyl methylcellulose HME 4 M) was passed through the extruder at 50 rpm with a processing temperature of115°C. The resulting extrudates were pelletized with a die-surface cutting pelletizer. Finally, the pellets were coated with Eudragit S 100 solution until they attained a 10% weight gain. These pellets were evaluated for the drug’s physical state using thermal analysis, in-vitro drug release in simulated gastrointestinal fluids, and KTP stability under accelerated storage conditions.

Results: The powder X-ray diffraction (Fig. 1) and differential scanning calorimetry results indicate that KTP is present in a solid-solution state within the polymeric matrix after HME. From the in-vitro drug release studies (Fig. 2), the F2 formulation showed 15.1±0.6 % drug release in the lag period (5 h), which can be further reduced to about 1.2±0.2 % utilizing Eudragit S 100 coating (F4 formulation). Coating the pellets with Eudragit help prevent premature drug release in the upper gastrointestinal system and thus leave a majority of drug available to be released in the colon. Both F2 and F4 formulations demonstrated a prolonged release lasting up to 24 hours in the colonic region, as supported by the mean dissolution time and efficiency. After undergoing accelerated stability studies at 40°C temperature and 75 ± 5% RH for 6 months, the F4 formulation proved its stability in assay and drug release studies.

Conclusion: In conclusion, developing colon-specific KTP Eudragit-coated hot-melt extruded pellets could be vital to gain maximum drug release in the colonic region without significant drug loss in the upper gastrointestinal tract.

References: 1. Vemula, S.K., Formulation and pharmacokinetics of colon-specific double-compression coated mini-tablets: Chronopharmaceutical delivery of ketorolac tromethamine. International Journal of Pharmaceutics. 2015. 491(1-2): p. 35-41.
2. Narala, S., Repka, M.A., et al., Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting. International Journal of Pharmaceutics: X. 2023. 5: p. 100156.

Table 1: Formulation and in-vitro drug release parameters of KTP pellets

Figure 1. Powder X-ray diffractograms of a) KTP, b) HM Pectin, c) F4 formulation pellets

Figure 2. Drug release profiles of KTP colon-specific release pellets