Challenges encountered in the transfer of atorvastatin tablet manufacturing - commercial batch-based production as a basis for small-scale continuous tablet manufacturing tests.

As is the case with batch-based tableting processes, continuous tablet manufacturing can be conducted by direct compression or with a granulation step such as dry or wet granulation included in the production procedure. In this work, continuous manufacturing tests were performed with a commercial tablet formulation, while maintaining its original material composition. Challenges were encountered with the feeding performance of the API during initial tests which required designing different powder pre-blend compositions. After the pre-blend optimization phase, granules were prepared with a roller compactor. Tableting was conducted with the granules and an additional brief continuous direct compression run was completed with some ungranulated mixture. The tablets were assessed with off-line tests, applying the quality requirements demanded for the batch-manufactured product. Chemical maps were obtained by Raman mapping and elemental maps by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Large variations in both tablet weights and breaking forces were observed in all tested samples, resulting in significant quality complications. It was suspected that the API tended to adhere to the process equipment, accounting for the low API content in the powder mixture and tablets. These results suggest that this API or the tablet composition was unsuitable for manufacturing in a continuous line; further testing could be continued with different materials and changes in the process.

3D printed oral solid dosage form: Modified release and improved solubility.

Oral solid dosage form is currently the most common used form of drug. 3D Printing, also known as additive manufacturing (AM), can quickly print customized and individualized oral solid dosage form on demand. Compared with the traditional tablet manufacturing process, 3D Printing has many advantages. By rationally selecting the formulation composition and cleverly designing the printing structure, 3D printing can improve the solubility of the drug and achieve precise modify of the drug release. 3D printed oral solid dosage form, however, still has problems such as limitations in formulation selection. And the selection process of the formulation lacks scientificity and standardization. Structural design of some 3D printing approaches is relatively scarce. This article reviews the formulation selection and structure design of 3D printed oral solid dosage form, providing more ideas for achieving modified drug release and solubility improvement of 3D printed oral solid dosage form through more scientific and extensive formulation selection and more sophisticated structural design.

Streamlining tablet lubrication design via model-based design of experiments.

In oral solid dosage production through direct compression powder lubrication must be carefully selected to facilitate the manufacturing of tablets without degrading product manufacturability and quality (e.g. dissolution). To do so, several semi-empirical models relating compression performance to process operating conditions have been developed. Among them, we consider an extension of the Kushner and Moore model (Kushner and Moore, 2010, International Journal Pharmaceutics, 399:19) that is useful for the purpose, but requires an extensive experimental campaign for parameters identification. This implies the preparation and compression of multiple powder blends, each one with a different lubrication extent. In turn, this translates into a considerable consumption of Active Pharmaceutical Ingredient (API), and into time-consuming experiments. We tackled this issue by proposing a novel model-based design of experiments (MBDoE) approach, which minimizes the number of optimal blends for model calibration, while obtaining statistically sound parameters estimates and model predictions. Both sequential and parallel MBDoE configurations were compared. Experimental results involving two placebo blends with different lubrication sensitivity showed that this methodology is able to reduce the experimental effort by 60-70% with respect to the standard industrial practice independently of the formulation considered and configuration (i.e. parallel vs. sequential) adopted.

Pharmaceutical Lauryl Sulfate Salts: Prevalence, Formation Rules, and Formulation Implications.

The anionic surfactant sodium lauryl sulfate (SLS) is known to deteriorate the dissolution of some drugs by forming poorly soluble lauryl sulfate (LS) salts. However, because of the perception of its infrequent occurrence, this phenomenon is usually not investigated in drug development until unexpected dissolution slowdown is encountered. This work demonstrates the prevalence of this phenomenon, where 14 out of 18 compounds with diverse chemical structures, including salts of basic drugs, a quaternary ammonium salt, organic bases, and zwitterionic molecules, precipitated from a solution when mixed with SLS. Although no precipitation was observed for the other 4 compounds, their FTIR spectra suggested 3 of them had intermolecular interactions with SLS when dried from a solution. These results, along with the 5 other examples reported in the literature, demonstrate the prevalence of this phenomenon. The occurrence of precipitation is thermodynamically driven by the relative difference between the ion product in solution (Q) and the solubility product of the lauryl sulfate salt (Ksp). SLS, as a surfactant, also affects precipitation kinetics by influencing the interfacial tension of nuclei of the insoluble salt. When a potential issue associated with the LS salt is identified, effective mitigation strategies should be proactively designed and implemented to alleviate its possible negative impact on drug dissolution.

In vitro comparison test for chemical solid oral generic drugs administered by nasogastric tubes / 国际药学研究杂志

At present, the dosage and administration items in the marketing instructions of some oral solid brand drugs approved in China include related contents for administration via nasogastric tube. In order to achieve consistency with the original drugs in quality and efficacy, the generic drugs investigators should confirm whether the generic drugs and the original drugs have the same in vitro characteristics under the conditions of administration by nasogastric tube. The purpose is to eliminate the clinical risks brought by the way of administration. This article summarizes the experimental design and evaluation points for the in vitro comparative study of the solid oral generic drugs which can be administered by nasogastric tube, while referring to the individual drug guidelines issued by FDA and the related literature published, so as to provide a reference for the technical system construction for the consistency evaluation of oral solid dosage forms.