Tobias Werk

An Impedance-Based Method to Determine Reconstitution Time for Freeze-Dried Pharmaceuticals

The reconstitution of freeze-dried products is usually determined by visual inspection with the naked eye. This can inevitably lead to significant variability in the ability to detect complete reconstitution of the dried solid. It was thus the goal of our study to assess an automated method to monitor reconstitution of a freeze-dried protein drug product in its primary packaging. A newly developed measuring device was used to measure impedance. This was achieved by detecting minor changes in impedance of the reconstitution medium, which occurred because of solid material dissolving during the dissolution process. This measurement system was capable of consistently detecting the dissolution of the last visible residues of freeze-dried lyophilisates. The endpoint of reconstitution was defined at an impedance change of less than 1 Ω for at least 7 s. Finally, we compared reconstitution times determined by the automated impedance method with results obtained by a visual method. In contrast to human operators, the new method delivered both accurate and precise results. Besides detection of the reconstitution endpoint, the impedance method and apparatus can monitor reconstitution endpoints as well as reconstitution kinetics. This standardized method can therefore advantageously be used for the determination of the reconstitution endpoint.

Technology, Applications, and Process Challenges of Dual Chamber Systems

Dual-chamber systems provide an option as a drug and device combination product, when home care and emergency lyophilized products are intended. Nevertheless, until today, there are only a few products on the market, due to the challenges and limitations in manufacturability, product formulation, and product stability in a dual-chamber configuration, as well as economic considerations. This review serves to describe currently available dual-chamber systems and to discuss factors to be considered for appropriate selection and establishing fill-finish processes.

A Method To Determine the Kinetics of Solute Mixing in Liquid/Liquid Formulation Dual-Chamber Syringes

Dual-chamber syringes were originally designed to separate a solid substance and its diluent. However, they can also be used to separate liquid formulations of two individual drug products, which cannot be co-formulated due to technical or regulatory issues. A liquid/liquid dual-chamber syringe can be designed to achieve homogenization and mixing of both solutions prior to administration, or it can be used to sequentially inject both solutions. While sequential injection can be easily achieved by a dual-chamber syringe with a bypass located at the needle end of the syringe barrel, mixing of the two fluids may provide more challenges. Within this study, the mixing behavior of surrogate solutions in different dual-chamber syringes is assessed. Furthermore, the influence of parameters such as injection angle, injection speed, agitation, and sample viscosity were studied. It was noted that mixing was poor for the commercial dual-chamber syringes (with a bypass designed as a longitudinal ridge) when the two liquids significantly differ in their physical properties (viscosity, density). However, an optimized dual-chamber syringe design with multiple bypass channels resulted in improved mixing of liquids. LAY ABSTRACT: Dual-chamber syringes were originally designed to separate a solid substance and its diluent. However, they can also be used to separate liquid formulations of two individual drug products. A liquid/liquid dual-chamber syringe can be designed to achieve homogenization and mixing of both solutions prior to administration, or it can be used to sequentially inject both solutions. While sequential injection can be easily achieved by a dual-chamber syringe with a bypass located at the needle end of the syringe barrel, mixing of the two fluids may provide more challenges. Within this study, the mixing behavior of surrogate solutions in different dual-chamber syringes is assessed. Furthermore, the influence of parameters such as injection angle, injection speed, agitation, and sample viscosity were studied. It was noted that mixing was poor for the commercially available dual-chamber syringes when the two liquids significantly differ in viscosity and density. However, an optimized dual-chamber syringe design resulted in improved mixing of liquids.