Characterisation of mini-tablets – Pediatrics

Mini-tablets are a pharmaceutical dosage form with a diameter of typically ≤ 3 mm. This is a potential dosage form for pediatrics since the small size of mini-tablets can ease the swallowing of medicines. In recent years there has been an increasing demand for research and development concerning child-appropriate dosage forms. The goals are to improve the availability of approved medicines for children and increase the knowledge of medication use in the pediatric population. An important step in the manufacturing process is assessing the quality of the final product. Until know there has been an insufficient availability of standardized evaluation procedures concerning mini-tablets in the pharmacopoeias.

The aim of the study was to evaluate whether the disintegration and dissolution methods used in this present study could be recommended for usage in future evaluation procedures on mini-tablets. An additional aim was to assess the impact of compaction pressure (50 or 150 MPa), compaction speed (20 or 50 strokes/min) and amount of model drug (1 or 10 % w/w) on the characteristics of the mini-tablets. Furthermore, the drug-binding tendency of three membrane filters; Polytetrafluoroethylene (PTFE), Polyvinylidene fluoride (PVDF) and Nylon was investigated to evaluate which filter/filters that could be recommended for usage in future dissolution tests.

Mini-tablets were produced in a single-punch tablet press and sodium salicylate served as the model drug compound. The following tablet characterization tests were performed to assess the characteristics of the final products: uniformity of weight, uniformity of content, radial tensile strength, friability and disintegration and dissolution tests. Dissolution tests were performed on a mini paddle apparatus and compared with results retrieved from a conventional paddle apparatus. A petri dish filled with 40 mL phosphate saline buffer was used as the experimental set up in the disintegration tests.

All six batches passed the disintegration test and the test for uniformity of weight. Radial tensile strength was only determined on tablet batches produced at 150 MPa, and these batches also passed the friability test. Four out of six batches displayed an insufficient homogeneity in the initial tests for content uniformity. In the dissolution tests, usage of the mini paddle and the standard paddle equipment resulted in similar dissolution profiles. When evaluating the membrane filters, the highest drug recoveries were obtained with the PTFE and PVDF filters. The PVDF and PTFE filters can be recommended for usage in future dissolution tests due to their low drug binding- tendencies. Saturation of the PTFE and PVDF filters had no significant effect (p>0.05) on the drug recovery.

Only the two batches produced at 150 MPa were subjected to all characterization tests while the fragileness of the other four batches made them unsuitable as pharmaceutical dosage forms. The compaction pressure had the greatest impact on the characteristics of the mini-tablets. No correlations were detected when analyzing the impact of compaction speed or the impact of concentration of model drug on the tablet characteristics.

The disintegration method used in this present study is a potential method for future characterization tests on mini-tablets. To further evaluate the suitability of this method, comparisons of different procedures must be made in future characterization studies on mini-tablets. The dissolution method used in this present study can be recommended for future characterization tests. The development of a dissolution procedure is dependent on the characteristics of the investigated drug compound. It is important to assess the physical and chemical characteristics of the mini-tablet when determining the different settings of the dissolution test. Download the full thesis here: characterization-of-minitablets-1.pdf

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