Assessment of Abrasion-Induced Visual Defects in Twin Screw Wet Granulation Using Wall Friction Measurements

Starting point of the presented study were abrasion effects occurring during a twin screw wet granulation (TSG) process of a new chemical entity (NCE) formulation, resulting in gray spots on the final tablets. Several actions and systematic changes of equipment and process parameter settings of TSG process were conducted which reduced the visual defect rate of the tablets, i.e., gray spots on the surface, below the specification limit. To understand the rationale and mechanism behind these improvements, correlations of defect rates and wall friction measurements using a Schulze ring shear tester were evaluated. To check the suitability of the method, a broad range of wall materials as well as powder formulations at various moisture levels were investigated with regard to their wall friction angle. As differences in wall friction angle could be detected, further experiments were conducted using wall material samples made out of different screw materials for TSG. Evaluation of these screw wall material samples gave first hints, which screw materials should be preferred in regard of friction for TSG process. In the finally presented case study, wall friction measurements were performed using the above mentioned NCE formulation with known abrasion issues at TSG processing. The results confirmed that changes which led to a reduced visual defect rate of tablets correlated with a decreased wall friction angle. The results suggest wall friction measurements as a potent tool for equipment selection and establishment of a suitable process window prior to conducting TSG experiments. Graphical abstract

Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug.