Novel Glyceryl Monostearate- and Polyethylene Glycol 6000-Based Ibuprofen Pellets Prepared by Hot-Melt Extrusion: Evaluation and Stability Assessment

Abstract

Purpose: To prepare stable sustained-release (SR) pellets, containing high ibuprofen (IBU) loading, by hot-melt extrusion (HME) technique using polyethylene glycol 6000 (PEG 6000) and glyceryl monostearate (GMS). Methods: HME pellets (60% w/w IBU) were prepared using PEG 6000, GMS, and mixture of both polymers (1:1). Stability studies were performed under stress conditions (40 °C and relative humidity “RH” of 75%) for 6 months and at room temperature for 12 months. Fresh and stored IBU pellets were evaluated by drug content (HPLC), release rate study (USP apparatus IV), DSC, and XRD. Results: HME succeeded to produce SR-IBU pellets with high drug loading. PEG 6000 gave higher IBU release rate and relatively unstable formula after storage. PEG 6000/GMS mixture gave prolonged IBU release up to 4 h with stable formula for 12 months at room temperature. While, IBU/GMS pellets gave SR profile up to 6 h and a stable formula under both testing conditions. These advantages of IBU/GMS pellets could be an excellent candidate for SR-IBU product. DSC and XRD analysis data (enthalpy and counts) for IBU and polymers gave a mirror image for IBU release profiles of the studied HME pellets, for both fresh and stored samples. Conclusion: Stable SR-IBU/GMS HME pellets with high IBU loading (60% w/w) were successfully produced, for the first time, without any other excipients.