Mechanism by Which Magnesium Oxide Suppresses Tablet Hardness Reduction during Storage

Abstract

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...

Appropriate usage of food thickening agents to prevent non-disintegration of magnesium oxide tablets

“…Additionally, the disintegration time of the moisture-absorbed magnesium oxide tablets in Hightoromeal was shorter than that of newly opened tablets in Hightoromeal. It has been reported that voids in magnesium oxide tablets are decreased when the tablets absorb moisture 19,20 . This was because, although Hightoromeal easily invades newly opened tablets, the invasion of thickener into moisture-absorbed tablets may be difficult.…”

Quality Evaluation of Humidified Magnesium Oxide Tablet Formulations with Respect to Disintegration Time Prolongation

“…2,4-8) Sakamoto et al reported that MgO dissolved by moisture absorption forms solid crosslinks with powder particles as one of the mechanisms. 3) Moreover, they suggested that a part of MgO binds to water (H 2 O) and carbon dioxide (CO 2 ) to generate a hydromagnesite [Mg 5 (CO 3 ) 4 (OH) 2 •4H 2 O], which is involved in the formation of solid crosslinks. 4) In another study, physical structure, such as the presence or absence of voids, was also considered a factor in prolonging disintegration time.…”

“…1) In addition, there are some reports that the hardness and mass of MgO tablet formulations tend to increase when stored under humidified conditions and that disintegration of the MgO tablet formulations is prolonged by humidification. [2][3][4][5][6][7][8] Prolonged disintegration time of MgO tablet formulations affects patient's sense of taking. Furthermore, it is difficult for patients with insufficient swallowing ability to take the formulations.…”

Effect of Different Direct Compaction Grades of Mannitol on the Storage Stability of Tablet Properties Investigated Using a Kohonen Self-Organizing Map and Elastic Net Regression Model

“…We thought the values of the tested tablet properties mainly fluctuated according to the moisture content of the tablets. In other words, these values should be constant as long as the moisture content reaches a level of saturation after storage under humid conditions [16][17][18]. For example, Yamazaki et al [18] studied the storage stability of original brand name and generic famotidine tablets after storage under humid conditions (27 • C, 55% RH) for 8 weeks.…”