Two-step solid lipid extrusion as a process to modify dissolution behavior

Abstract

Extrudates based on varying ratios of the triglyceride tripalmitin and the hydrophilic polymer polyethylene glycol as matrix formers were produced as oral dosage forms with controlled release characteristics. The extrudates were processed below the melting points of the excipients and contained the hydrophobic model drug chloramphenicol. The influence of the ratio of the matrix formers on drug dissolution was investigated, with an increase in the water-soluble polymer content increasing the drug release rate. In addition, the effect of varying the extrusion process on the extrudate structure and drug dissolution was investigated. Two-step extrusion was performed, which comprised an initial extrusion step of drug and one matrix component followed by milling these extrudates and a second extrusion step for the milled extrudates mixed with the second matrix component. Initial extrusion with polyethylene glycol led to increased dissolution rates, while initial extrusion with tripalmitin led to decreased dissolution rates compared to the dissolution characteristics of extrudates containing the same composition produced by one-step extrusion. Thus, two-step solid lipid extrusion can successfully be used as a process to modify the dissolution behavior of extrudates.

Fig. 1

Physical characterization of powders and extrudates. a DSC thermograms of powders, b DSC thermograms of extrudates, and c XRPD diffractograms of powders and extrudates

Fig. 2

Dissolution curves of extrudates containing 50% chloramphenicol (PEG polyethylene glycol), n = 3, mean, SD < 3%, not shown

Fig. 3

DSC thermograms of extrudates containing 50% chloramphenicol produced by varying extrusion processes

Fig. 4

Dissolution curves of extrudates containing 50% chloramphenicol produced by varying extrusion processes (PEG polyethylene glycol), n = 3, mean, SD < 3%, not shown

Fig. 5

SEM images of extrudates before and after dissolution testing. Initially extruded with tripalmitin before (a) and after (b) dissolution, no initial extrusion before (c) and after (d) dissolution, initially extruded with polyethylene glycol before (e) and after (f) dissolution

Fig. 6

Stability testing of extrudates containing 50% chloramphenicol. a DSC thermograms after 3 months storage in 40°C/75% RH and b vapor sorption analysis