(M0930-08-53) Advancements in Mini-Tablets: High Drug Loading and Precise Dose Titration

Purpose: Mini-tablets have gained popularity due to their flexibility in dosing and ease of administration. Our research has focused on developing mini-tablets with high drug loading content that enabling precise dose titration. The use of mini-tablets with high drug loading content and reduced excipient burden has the potential to improve patient compliance and reduce manufacturing costs, making them an attractive option for pharmaceutical companies. This contribution showcases the strategies of mini-tablet manufacture, including formulation strategies, processing methods, and performance evaluations. Additionally, it highlights the advantages and challenges associated with this approach and provides insights into future developments.

Methods: Mini-tablets with a diameter of 2 mm and various drug loadings were produced using a tableting machine (NP-RD10A, Natoli Engineering Company, Inc., Saint Charles, United States) equipped with 10-tip punches through direct compression. To ensure good flow properties, the active pharmaceutical ingredient (API) was processed through dry granulation. Each mini-tablet was designed to represent the smallest strength of the API, so the desired dosage could be achieved by multiplying the number of sub-units. Dissolution tests were conducted using a paddle dissolution apparatus (708-DS, Agilent Technologies, United States). The concentration of the released drug was measured by its UV absorbance at ten different time points (2, 5, 10, 15, 20, 25, 30, 45, 50, and 60 minutes). The radial tensile strength of individual mini-tablets was determined using a texture analyzer (CTX, Brookfield Inc., Middleboro, United States). A constant speed of 0.1 mm/s was set, and the force required to crush the tablet was measured using a cylindrical probe with a diameter of 6 mm. The length of the mini-tablets was characterized by analyzing images taken by a microscope (BX41, Olympus Corporation, Tokyo, Japan) with a Plan x4 objective. The friability test was performed using a tablet friability apparatus (FT 2, Dr. Schleuniger Pharmatron, Switzerland). Forty mini-tablets were initially dedusted and weighed before being placed in the friabilator drum. In addition, approximately six and a half grams of placebo-coated mini-tablets with a diameter of 2 mm were also inserted into the apparatus along with the mini-tablets containing the API. The mini-tablets were subjected to 100 rotations in the friabilator drum, which lasted four minutes as the rotational speed was set to 25 rpm. Finally, the mini-tablets containing the API were separated, dedusted, and weighed.

Results: The granulation of active pharmaceutical ingredients enhanced the flow properties of tableting mixtures and resulted in improved mass uniformity. Through our successful efforts, we were able to formulate mini-tablets with high drug loading content that maintained the original drug dissolution profiles and met the necessary mechanical property criteria. Furthermore, we conducted evaluations to assess the influence of drug loading on compressibility, dissolution, and flow properties for both active pharmaceutical ingredients.

Conclusion: In this study, we investigated the formulation of two active pharmaceutical ingredients (APIs) into mini-tablets, which are commonly used in combination therapy. We optimized the formulation and process conditions to ensure proper dissolution and mechanical properties. The mini-tablets were specifically designed as unit dosage forms, containing the lowest strength of the APIs, which allows precise dose titration by multiplying the number of mini-tablets. Additionally, these prepared mini-tablets can be utilized as sub-units for Multi-Unit Pellet Systems, which can solve some problems related to the polypharmacy.