The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process

Abstract

Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.

Insights from a qualitative study of the procurement and manufacture of active pharmaceutical ingredients in India

“…Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body.’15 The manufacture of APIs from raw ingredients entails several intermediate stages, which often takes place in different production facilities, moving between countries in the process 16. The finished API is then combined with excipients, chemically inactive substances that help the medication remain stable and control absorption when the medicine is administered 17. Both APIs and excipients are crucial to the formation of an efficacious finished product.…”

“…16 The finished API is then combined with excipients, chemically inactive substances that help the medication remain stable and control absorption when the medicine is administered. 17 Both APIs and excipients are crucial to the formation of an efficacious finished product. Most research to date has focused on the latter stages of medicine production: the combination of API and excipients (and packaging) to create the finished product, thereby overlooking the complexities and potential vulnerabilities that occur further upstream.…”

Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

“…Continuous mixers have been shown to produce a more homogeneous output compared with mixers operating in a batch mode [ 74 ] and also have the added advantage of the potential to add PAT. Ervasti et al [ 75 ] considered whether one of the reasons for the slow take-up of CM might be due to concerns over which products it was most suited. On this basis, they studied the application of a CM direct compression process to low-dose API products, where achieving good homogeneity is a real challenge.…”

Formulation Study of a Co-Processed, Rice Starch-Based, All-in-One Excipient for Direct Compression Using the SeDeM-ODT Expert System

“…Among the general tablet manufacturing methods, direct compression (DC) stands the most prominent due to the cost-effectiveness, simplicity, and high stability it offers to the drug products [4]. However, manufacturing without a granulation process and recent advancement in pharmaceutical tableting, such as continuous manufacturing and high-speed tableting machines, could limit this production method with the conventional excipients [5,6]. Simultaneously, it encourages the development of a new excipient to support tablet manufacturing under specific production conditions.…”