The influence of tablet size and weight on water-based microwave-induced in situ amorphization

Abstract

Microwave-induced in situ amorphization is an innovative technology that enables the direct preparation of amorphous solid dispersions (ASDs) in the final dosage form. This approach offers significant advantages in addressing the challenges related to the long-term physical stability and downstream processing of ASDs. However, most previous studies have primarily focused on regular tablet sizes intended for adult patients. In light of the unique considerations and challenges associated with paediatric formulations, this study aimed to investigate the impact of tablet sizes with varying weights on microwave-induced in situ amorphization.

The overall objective was to establish a novel platform for personalized formulations that cater specifically to paediatric patients with improved drug dissolution rate and enhanced patient compliance. Indomethacin (IND) was chosen as a model drug while PVP/VA 64 was selected as the polymeric carrier to prepare ASDs with 20 % (w/w) drug loading. Different-sized tablets (6 mm, 4 mm, and 2 mm which were considered as mini-tablets intended for paediatric patients) were characterized using a combination of imaging, structural and thermal analyses, followed by in vitro dissolution testing. With 2 mm mini-tablets, in particular, varying numbers of mini-tablets (one to five) were placed into an HPMC capsule which was then exposed to microwave irradiation.

It was observed that a complete amorphization accompanied with an improved dissolution rate was achieved for formulations of all tablet sizes in this study. Regardless of tablet size, there were no significant differences in the extent of dissolution rate enhancement. In addition, a white-to-yellow colour change indicating amorphization of IND and a marked tablet deformation were observed in all formulations after microwaving. Among all 2 mm mini tablet formulations in capsules, the 5-in-1 formulation showed the highest amorphization rate. Overall, the in-situ amorphization platform proposed in this study can be applied to tablets with varying diameters down to 2 mm and weights down to 4 mg, indicating a promising paediatric formulation strategy.

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Materials

Crystalline IND (MW = 357.79 g/mol) was purchased from Fagron (Rotterdam, Netherlands). Copovidone (Kollidon® PVP VA 64) was provided by BASF (Ludwigshafen, Germany). Magnesium stearate (Fagron, Barsbüttel, Germany), were used as a glidant to increase flow between powders. Silica gel with indicator (orange gel) was bought from Supelco (Darmstadt, Germany) for storage. VCAPS hydroxypropyl methylcellulose (HPMC) capsules (size 0) were gifted by Capsugel® Lonza (Basel, Switzerland).

Meng Zhang, Korbinian Löbmann, Gavin P. Andrews, Min Zhao, The influence of tablet size and weight on water-based microwave-induced in situ amorphization, International Journal of Pharmaceutics, 2025, 126303, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.126303.

At CPhI 2025 in Frankfurt we had the chance for an introduction interview with Argann Pensec from Lactalis Ingredients Pharma: