Segregation of Formulated Powders in Direct Compression Process and Evaluations by Small Bench-Scale Testers

Powder segregation can cause severe issues in processes of pharmaceutical drugs for control of content uniformity if the powder is likely to be free or easy flowing. Assessing segregation intensity of formulated powders in a process is challenging at the formulation stage because of the limited availability of samples. An advanced segregation evaluation using small bench-scale testers can be useful for formulation decisions and suggestions of operation conditions in the process, which has not been practically investigated before. In this study, eight formulations (two co-processed excipients blended with one active pharmaceutical ingredient at different ratios) were used for the segregation study on two types of bench-scale testers (air-induced and surface rolling segregation tester), and a pilot simulation process rig as a comparative study.

Highlights

• Segregation of formulated powders in a direct compression process,
• Assess powder segregation in a process using bench-scale testers,
• Validation of segregation index measured from bench-scale testers with process rig,
• Segregation on bench-scale tester is highly correlated to the segregation in process,
• A prediction model was established based on segregation harshness factors,
• Measured segregation index on bench-scale testers linearly correlated to process rig.

The results show that segregation measured on the bench-scale testers can give a good indication of the segregation intensity of a blend if the segregation intensity is not more than 20%. The comparison also shows that both the bench-scale testers have a good correlation to the process rig, respectively, which means either segregation tester can be used independently for the evaluation. A linear regression model was explored for prediction of segregation in the process.

Table 2: A list of the formulations studied and suppliers of the materials

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Materials

One API and two Co-Processed Excipients (CPEs) were used to form eight formulations at different mixing ratios, as shown in Table 2. The API/CPEs were supplied by various suppliers, as shown in Table 2, with the material codes used in the analysis and corresponding names with their formulations. Because of availability and safety, acetaminophen dense is selected for this study as a typical API material which is a widely used nonprescription analgesic and antipyretic medication for mild-to-moderate pain and fever. A CPE used to be a combination of two or more excipients obtained by physical co-processing that does not lead to the formation of covalent bonds (Bhatia, et al., 2022). Because of the functionalities that are not achievable through sample blending, nowadays CPEs are widely used in many pharmaceutical products to avoid complicated blending process (Mamatha et al., 2017, Zhao et al., 2022). A mixture of an API and a CPE will be more representative for practical applications and simple for the study. In this study, CPEs used are the Ludipress® and the Prosolv® EasyTab SP. Ludipress® Polymer is a mixture of Lactose monohydrate (93%), Kollidon® 30 and Kollidon® CL supplied as white, free-flowing granules. PROSOLV® EASYtab SP is a lubricant-coated high functionality excipient composite, which is comprised of four individual components: a binder/a filler, a glidant, a super disintegrant, and a lubricant as Microcrystalline Cellulose (96%), Colloidal Silicon Dioxide, Sodium Starch Glycolate, and Sodium Stearyl Fumarate.

Tong Deng, Lucas Massaro Sousa, Vivek Garg, Michael SA Bradley, Segregation of Formulated Powders in Direct Compression Process and Evaluations by Small Bench-Scale Testers, International Journal of Pharmaceutics,
2023, 123544, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123544.

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