11 mm process 11

Caffeine citrate (20% w/w) was blended with EC, triethyl citrate (TEC) and with or without pore formers in an amount outlined in Table 1 using a V-shell blender (GlobePharma, Maxiblend, New Brunswick, NJ, USA) after passing through ASTM #30 mesh. The blends were melt-extruded using a co-rotating twin-screw extruder (11 mm Process 11, ThermoFisher Scientific, Pittsburgh, PA, USA) with a modified screw design at 50 rpm over a temperature range of 125–130°C. The extrudate was milled using a comminuting mill (Fitzpatrick, Model “L1A”, Elmhurst, IL, USA) and sieved through an ASTM # 40/35. The portion retained by an ASTM # 35 sieve was stored in foil lined polyethylene bags for further analysis and processing.

Preparation of RX-HCL loaded NLCs using HME technology involved two main steps. The first step involved the formation of a pre-emulsion by extruding a combination of solid lipid, RX-HCl, liquid lipid, and the aqueous phase through the HME barrel, and the second step involved size reduction of the pre-emulsion utilizing probe sonication to obtain the NLC formulation. Extrusion was carried out on an 11-mm co-rotating twin screw extruder (11-mm Process 11^™, Thermo Fisher Scientific, Karlsruhe, Germany). Schematic representation of the preparation of the NLC formulations using HME and probe sonication is as shown in Figure 1. RX-HCl was uniformly mixed with the solid lipid, and introduced in the barrel using a volumetric feeder. Liquid lipid and the aqueous phase (solution of surfactants and water) were heated to 85 °C and then respectively, injected in zone 2 and zone 4 of the barrel using peristaltic pumps. A screw speed of 100 rpm, barrel temperature of 85 °C, and sonication time of 10 minutes, were used in this study. Volumetric feeder and peristaltic pump feeding rates were optimized in this study. Figure 2 shows the screw configuration that was used for the extrusion process [3 (link)]. The pre-emulsion obtained was subjected to probe sonication (SONICS Vibracell^™, Sonics and Material, Inc., Newton, CT) with an amplitude of 40 %, to obtain the RX-HCl loaded NLCs.

During the preformulation studies, the HME parameters such as barrel temperatures (100, 160, 180 °C), screw configurations (three mixing zones and only conveying zone), and screw speeds (25 and 100 rpm) were investigated to find out which parameters that have dominant impact on ATR transformation to an amorphous state. After the evaluation of HME parameters, ATR (25%) and NUS2 (75%) were mixed and blended using a V-shell blender (MaxiBlendTM, GlobePharma, North Brunswick, NJ, USA) at 25 rpm for 10 min. The physical mixture (PM) was fed on to a corotating twin-screw extruder (11 mm Process 11^™, Thermo Fischer Scientific, Karlsruhe, Germany) without an extrusion die and successfully extruded at 180 °C. The screw designs were a Thermo Fischer standard screw design with three mixing zones (Fig. 1A) and a screw design with only conveying elements (Fig. 1B) without any mixing zones. Two feed rates (FR) were studied, and the HME proposed formulations are shown in Table 1. All formulations output was in a powder form.