The impacts of roller compaction on the quality attributes of simultaneously compressed micro and minitablets

The challenges of developing good quality low dose minitablets was assessed by systematically studying the effects of ibuprofen (IBU, a model compound) particle sizes (6–58 µm D₅₀) and concentrations (0.1–3 %w/w), roller compaction forces (3–7 kN/cm), and the minitablet size. A novel compression approach, where three minitablet sizes (1.2, 1.5, and 2 mm) were simultaneously produced in a single compression run was used. Roller compacted ribbons, granules, minitablets were characterized for physico-mechanical properties and minitablets were also characterized for stratified content uniformity and weight uniformity.

The results showed that roll force was the more dominant factor to ribbon solid fraction or tensile strength and granule size enlargement. Minitablets obtained from the granules had good weight uniformity; all but one batch met the <Ph. Eur. 2.9.5 >criteria. The precise control of tooling lengths across the various sizes was found profoundly important for achieving expected weights, solid fraction, and tensile strength of the simultaneously produced minitablets. The roller compaction process considerably improved the CU variability of the minitablets as compared to the direct compression process. Smaller particle size and higher concentration of IBU, increased roller compaction force, and larger minitablet size improved the potency and content uniformity; however, only the minitablet size was a statistically significant factor in this study.

As a product strategic design criterion, a threshold of 25 minitablets in a dosage unit would ensure robust downstream filling and weight verification operations as well as dose accuracy and uniformity (would pass <USP 905> stage 1 criteria). This study results demonstrated feasibility of the novel simultaneous compression approach and the roller compaction process in developing good quality minitablets.

Materials

Ibuprofen was used as a model compound in this study. Three different particle size grades [25, 50, and 70) of IBU were obtained from BASF, NJ, USA. IBU grades 25 and 50 were used as is, whereas, the grade 70 was pin milled at 15000 rpm (Contraplex CWII, Hosokawa Micron Powder Systems, NJ, USA) to create the smallest particle size API. Particle size of pin milled, grade 25, and grade 50 IBU are listed in Table 1 (measured using Mastersizer 3000 Aero S particle analyzer, dry dispersion method.

Following excipients are mentioned in the study besides other: Microcrystalline Cellulose pH 102, anhydrous lactose, croscarmellose sodium, magnesium stearate

Bilge Selvi, Naseer Alam, Saikishore Meruva, Patrick Mwangi, Jason Sweeney, Darshan Parikh, Suliman Chawdry, Biplob Mitra, The impacts of roller compaction on the quality attributes of simultaneously compressed micro and minitablets, International Journal of Pharmaceutics, 2024, 124785, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124785.