Purpose: Polymeric excipients play an increasingly important role in modern formulation design. With well controlled molecular design and chemical functionalities, synthetic polymers contribute to quality attributes of the final dosage forms, such as controlled release, enhanced bioavailability and extended physical stability. Meanwhile, excipient could also significantly impact the processability of formulations in different formulation processes. Copovidone is a major solubilizer that is commonly used in HME to enhance the bioavailability of active pharmaceutical ingredient (API), and the goal of this study is to design and characterize an improved copovidone product that enables a better hot melt extrusion process than current standard copovidone,
Methods: In this study, a developmental grade of copovidone has been developed and characterized for powder flowability, HME processability and stability. These properties were compared with these of the standard copovidone. An extrusion study has been carried out using Leistrize 27 mm extruder, to further confirm the process advantages that the improved conpovidone offers over the standard grade of copovidone.
Results: The improved copovidone showed several advantages over standard copovidone. Specific benefits of using the improved copovidone in HME included but were not limited to the following:
1. The maximum HME throughput obtained by using improved copovidone was 17% higher than that of using current copovidone. In addition, no processing issue was observed by using the improved copovidone and consequently, the content uniformity of the extrudates was enhanced.
2. The pure polymer processing torque and die pressure at different processing temperatures were reduced by approximately 20% and 25%, respectively, when the improved copovidone was used. Similar trends were also observed in copovidone/API formulations.
3. Peroxide level of the improved copovidone was at least 50% lower than that of the current copovidone. Furthermore, the growth rate of the peroxide in improved copovidone was one order slower than current copovidone.
Conclusion: The improved copovidone exhibited both better processability and stability than standard grade of copovidone. At the same time, it exhibits the same API solubility and stability enhancements as the standard copovidone. All these benefits and properties associated with the improved copovidone makes it better suited to HME process, and thus improved extrusion efficiency and stability can be expected in extruded products when improved grade copovidone is used.