This study aimed to clarify the effects of magnesium oxide (MgO) on the hardness of orally disintegrating tablets (ODTs) during storage. ODTs containing a range of MgO concentrations were prepared by direct powder compression and stored for up to 4 weeks in an unpackaged condition at 40°C, with 75% relative humidity. Tablets that did not contain MgO showed a significant decrease in hardness after one week in storage, while those containing MgO at a mass fraction of ≥4% maintained their hardness for up to 4 weeks. The tablet disintegration times after storage were equivalent to those observed before storage (approximately 30 s), regardless of the MgO level. Furthermore, the dissolution behavior of a model drug (acetaminophen) from the ODTs was not affected by the level of MgO. These findings revealed that the addition of MgO suppressed the reduction in ODT hardness during storage in the unpackaged state, without delaying tablet disintegration or inhibiting drug release.

This study investigated how the inclusion of magnesium oxide (MgO) maintained tablet hardness during storage in an unpackaged state. Tablets were prepared with a range of MgO levels and stored at 40°C with 75% relative humidity for up to 14 d. The hardness of tablets prepared without MgO decreased over time. The amount of added MgO was positively associated with tablet hardness and mass from an early stage during storage. Investigation of the water sorption properties of the tablet components showed that carmellose water sorption correlated positively with the relative humidity, while MgO absorbed and retained moisture, even when the relative humidity was reduced. In tablets prepared using only MgO, a petal-or platelike material was observed during storage. Fourier transform infrared spectrophotometry showed that this material was hydromagnesite, produced when MgO reacts with water and CO 2 . The estimated level of hydromagnesite at each time-point showed a significant negative correlation with tablet porosity. These results suggested that MgO suppressed storage-associated softening by absorbing moisture from the environment. The conversion of MgO to hydromagnesite results in solid bridge formation between the powder particles comprising the tablets, suppressing the storage-related increase in volume and increasing tablet hardness.Key words hydromagnesite; relative humidity; unpackaged state; capillary condensation; mesopore Tablets are frequently used as a drug dosage form that is convenient for patients. However, uncoated tablets are affected by the temperature, humidity, and light-exposure of their storage environment; humidity in particular often affects the physical properties of tablets by reducing hardness and changing (accelerating or delaying) their disintegration time. [1][2][3][4] For this reason, uncoated tablets are usually packaged using materials with a high moisture resistance, such as pillowtype packaging with aluminum foil. In recent years, however, uncoated tablets have also often been handled in an unpackaged state, such as in automatic tablet packing machines, to provide unit-dose packages that aim to improve the reliability of, and compliance to, drug therapies. The packaging materials used for unit-dose packaging are not generally completely moisture-resistant, and the tablets in these packages reportedly show decreased hardness. 4,5) Magnesium oxide (MgO) has frequently been used as a laxative and antacid and has been proven to be effective and safe. MgO tablets have also become widespread in recent years because they are easy to take. [6][7][8] When stored for three months in an unpackaged state at 30°C with 75% relative humidity, these MgO tablets (Magmitt Tab ® , and Maglax Tab ® ) showed a 1.7-3.8-fold increase in hardness.9) MgO accounts for 86-88% of the mass of these tablets, strongly implying that MgO is involved in this increase in hardness. We have previously shown that MgO is useful as an excipient that suppresses the decline in tablet hardness caused by humidity.10)The...