Effects of polymorphic transformation on pharmaceutical properties of direct compressed tablets containing theophylline anhydrate bulk powder under high humidity

The effect of high humidity on the pharmaceutical properties of direct compression tablets containing theophylline anhydrate (TA) was investigated to prepare high quality pharmaceuticals. A mixed powder (230 mg) containing the TA, β-lactose anhydrate, microcrystalline cellulose (MCC) and magnesium stearate was compressed in a die by 8-mm diameter punches with flat surfaces at 4.8 kN. The TA tablets were stored in desiccators at 96% relative humidity and 20 °C. Physicochemical properties of the tablets were measured using, powder X-ray diffraction (XRD), X-ray computed tomography (XCT), the tablet hardness test and the dissolution test. The water absorption process could be divided into two stages: 1.0% absorption at for 0–6 h due to absorption of MCC, and 4% absorption at 6–24 h due to hydration of TA. The XRD and XCT results were supported be tablet weight changes in the initial and later stages, respectively. The relationship between tablet hardness and water absorption indicated that the first stage of absorption was more significant. In contrast, the relationship between the dissolved amount at 20 min (D20) and water absorption indicated that the first stage was less effective. The first stage of absorption was due to MCC, but the second was due to hydration of the TA bulk powder.