Optimizing twin-screw melt granulation: The role of overflight clearance on granulation behavior.

Twin-screw melt granulation (TSMG) relies on the dispersive and distributive mixing at the kneading zone for granule growth to happen highlighting the critical role played by the kneading elements in TSMG. Despite extensive research conducted on the impact of screw geometry in melt compounding, there is not enough literature for TSMG. Disc width for the kneading elements was 2 mm, contrary to the standard 5 mm. The objective of this study was to evaluate if varying overflight clearance (OC) can alter the paradigm for TSMG. The new elements reduce the peak shear at kneading zone however a higher barrel temperature and degree of fill (DoF) is required to compensate to attain similar granule attributes. The change in DoF was achieved through a combination of modified screw configuration to pre-densify powders before kneading and processing at a lower screw speed. Despite the higher barrel temperature, process optimization of thermally unstable gabapentin was carried out. Using the new elements, compressible granules (Tensile strength > 2 MPa) with low % GABA-L content were manufactured despite increasing OC to 0.4 mm. Granule stability at 40 °C, ambient humidity for 6 months indicated gabapentin was stable (% GABA-L ≪0.4 %) despite a high barrel temperature of 120 °C.

Feasibility of high melting point hydrochlorothiazide processing via cocrystal formation by hot melt extrusion paired fused filament fabrication as a 3D-printed cocrystal tablet.

The development of amorphous solid dispersions (ASDs) of high-melting-point drug substances using hot-melt extrusion (HME) continues to be challenging because of the limited availability of polymers that are stable at high processing temperatures. The main aim of this research project is to improve processability and develop three-dimensional (3D) cocrystal printlets of hydrochlorothiazide (HCTZ) using HME paired fused deposition modeling (FDM) techniques. Among the investigated coformers, nicotinamide (NIC) was identified as a suitable coformer. The cocrystal filaments of HCTZ-NIC and pure HCTZ that were suitable for the FDM 3D-printing process were developed using a Process 11 mm Twin -Screw Extruder with Kollicoat® IR and Kollidon® VA64 as polymeric carriers. The investigation of extruded filaments using differential scanning calorimetry (DSC) revealed the formation of HCTZ-NIC cocrystals, which was further confirmed using Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction analysis (PXRD). The 3D-printed printlets of HCTZ-NIC with 50 % infill density resulted in improved dissolution and permeability compared to pure drug. This demonstrates the suitability of the HME-paired FDM 3D-printing technique for improving solubility and developing on-demand patient-focused dosage forms for poorly soluble high-melting-point drug substances by utilizing a cocrystal approach.

A quality by design approach to develop topical creams via hot-melt extrusion technology.

The advantages of hot-melt extrusion technology (HME) over conventional techniques to develop topical semisolids have been established. However, this technique is not widely used for semisolid production. Therefore, the aim of this novel work was to develop creams using the melt extrusion technology while applying Quality by Design (QbD) principles to study the effects of the extrusion process parameters on the product characteristics. The model drug selected was hydrocortisone acetate. A 23 factorial design was considered for the factor influence study, which resulted in eight formulations to be extruded. Of the process parameters considered, the temperature of zone 2 had a significant influence on the work of adhesion of the creams. A similar permeation profile was obtained for all the formulations with the formulations following a diffusion based drug release mechanism. The results from the size distribution graph indicated stable cream formulations. In conclusion, this technology coupled with a design of experiments approach could be utilized to study how the extrusion process parameters could be modified to develop consistent topical creams with ideal product characteristics.

Solid-State Stability Issues of Drugs in Transdermal Patch Formulations.

The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used.