Stability characterization for pharmaceutical liposome product development with focus on regulatory considerations: An update.

Liposomes have several advantages, such as the ability to be employed as a carrier/vehicle for a variety of drug molecules and at the same time they are safe and biodegradable. In the recent times, compared to other delivery systems, liposomes have been one of the most well-established and commercializing drug products of new drug delivery methods for majority of therapeutic applications. On the other hand, it has several limitations, particularly in terms of stability, which impedes product development and performance. In this review, we reviewed all the potential instabilities (physical, chemical, and biological) that a formulation development scientist confronts throughout the development of liposomal formulations as along with the ways to overcome these challenges. We have also discussed the effect of microbiological contamination on liposomal formulations with a focus on the use of sterilization methods used to improve the stability. Finally, we have reviewed quality control techniques and regulatory considerations recommended by the agencies (USFDA and MHLW) for liposome drug product development.

Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets.

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. This study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets. The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules' density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.