医薬品の結晶水と錠剤に関する研究 (第1報)

パラアミノサリチル酸カルシウムの結晶水が錠剤におよぼす影響

抄録

Medicinal tablets of compounds containing water of crystallization often show variation in disintegration time by passage of time and various examinations are being made to solve this problem but no reports are available for fundamental reasons for this phenomenon.
Assuming that the moisture during preservation might be the reason for this phenomenon, relationship between the amount of crystal water in a compound and pressure-tabletting was examined from measured values in thermobalance, differential thermal analysis, specific gravity, and X-ray diffraction methods, using calcium p-aminosalicylate heptahydrate (PASCa⋅6H₂O).
PAS-Ca⋅6H₂O loses its water of crystallization according to atmospheric conditions. In this case, gram-volume decreases as indicated in Table I and, at the same time, the substance takes an amorphous state, not forming a crystal lattice even after a long period of time, as shown in Fig. 5. As indicated in Table II, supply of water to this anhydrate results in retention of crystal water in transition state but its X-ray diffraction pattern is still that of an amorphous state and lattice formation is observed only after a long period of time.
These facts suggest that when tablets are formed from a compound in partially amorphous state, the tablets absorb moisture during passage of time and gradually transits to crystal lattice of a hydrate, resulting in volume change of the crystal and promotion of tablet disintegration. This also results in decreased amount of retained air and gradual lengthening of disintegration time (Table III).