Department of Pharmaceutical Engineering, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
Int J Pharm. 2011 Sep 15;416(1):252-9. doi: 10.1016/j.ijpharm.2011.07.001. Epub 2011 Jul 7.
A major challenge in the development of orally disintegrating tablets (ODTs) is to achieve a good balance between tablet hardness and disintegration time. In this study, an advanced method was demonstrated to improve these opposing properties in a molded tablet using a one-step procedure that exploits the swelling induced by microwave treatment. Wet molded tablets consisting of the delta form of mannitol and silicon dioxide were prepared and microwave-heated to generate water vapor inside the tablets. This induced either swelling or shrinking of tablets, in the extent of each being dependent on tablet formulation and manufacturing conditions. A two-level full factorial design method was used to evaluate the effects of several variables in formulation and manufacturing conditions on the tablet properties, hardness, disintegration time and change in shape. The variables investigated in this study were: ratio of silicon dioxide in formulation, water volume added in granulation, ratio of water absorbed by silicon dioxide prior to granulation, and microwave irradiation time. Swelling of tablet by microwave irradiation was observed in the batches with high ratio of silicon dioxide and low levels of water volume. The disintegration time was clearly shortened by induction of the swelling, while tablet hardness increased. We demonstrated that the water vapor generated by microwave irradiation promoted a change in the crystalline form of mannitol from delta to beta, and that this may have contributed to an increase in tablet hardness. Additionally, it was found that new solid bridges were formed between the granules in the tablet via the pathway from dissolution of mannitol in water vapor to congelation, resulting in an increase in tablet hardness. Thus, both tablet hardness and disintegration properties of the molded tablets were improved by the proposed one-step method and the appropriate ranges for variables are indicated. In addition, multiple regression modeling was used to optimize formulation and manufacturing conditions, and the tablets obtained under these optimized conditions showed both swelling and desirable tablet properties. Therefore, we concluded that this one-step method using microwave irradiation would be a useful method for preparing the ODTs.
开发口崩片（ODT）的一个主要挑战是在片剂硬度和崩解时间之间取得良好的平衡。在这项研究中，展示了一种先进的方法，通过利用微波处理引起的膨胀，在模制片剂中改善这些相反的性质。使用一步法制备由甘露糖醇的δ形式和二氧化硅组成的湿模制片剂，并对其进行微波加热以在片剂内部产生水蒸气。这会引起片剂的膨胀或收缩，其程度取决于片剂配方和制造条件。使用两级完全因子设计方法评估配方和制造条件中的几个变量对片剂性质（硬度、崩解时间和形状变化）的影响。本研究中考察的变量有：配方中二氧化硅的比例、造粒中加入的水量、造粒前二氧化硅吸收的水量以及微波辐射时间。在高二氧化硅比例和低水量的批次中观察到片剂通过微波辐射膨胀。通过诱导膨胀，崩解时间明显缩短，而片剂硬度增加。我们证明了微波辐射产生的水蒸气促进了甘露糖醇从δ型向β型的晶型转变，这可能有助于提高片剂的硬度。此外，发现通过水蒸气中甘露糖醇的溶解到凝固的途径，在片剂中的颗粒之间形成了新的固体桥，从而导致片剂硬度增加。因此，通过提出的一步法，改善了模制片剂的片剂硬度和崩解性质，并且指示了变量的适当范围。此外，还使用多元回归建模优化配方和制造条件，并且在这些优化条件下获得的片剂表现出膨胀和理想的片剂性质。因此，我们得出结论，这种使用微波辐射的一步法将是制备 ODT 的有用方法。
