Physical characterization of dibasic calcium phosphate dihydrate and anhydrate.

The dehydration of different commercial brands of dibasic calcium phosphate dihydrate (DCPD; CaHPO(4).2H(2)O) was examined over a range of temperatures and water vapor pressures. To determine the main factors affecting the physical stability of DCPD, the baseline characterization of DCPD and dibasic calcium phosphate anhydrate (DCPA; CaHPO(4)) was conducted by thermogravimetric analysis, differential scanning calorimetry and X-ray diffractometry. The surface area and the DCPA content (present as an impurity) depended on the commercial source of DCPD. The larger particles contained a higher concentration of DCPA and the anhydrate exhibited a concentration-dependent acceleratory effect on the dehydration of DCPD. Unlike DCPD, DCPA is physically stable and resisted hydration even when dispersed in water for over 7 months in the temperature range of 4-50 degrees C. In dosage forms containing DCPD, there is a potential for phase transformation to DCPA, while the reverse transition, that is, DCPA --> DCPD appears to be extremely unlikely. Thus, the risk of physical transformation can be minimized by using DCPA in formulations.

Processing-induced phase transitions of theophylline--implications on the dissolution of theophylline tablets.

Aqueous wet massing of stable anhydrous theophylline (A) with polyvinylpyrrolidone (PVP) resulted in its complete transformation to theophylline monohydrate (M). Drying at 45 degrees C, resulted in the formation of metastable anhydrous theophylline (A*) which then transformed to A. PVP, a known crystallization inhibitor, was effective in inhibiting the A* --> A transition. The higher molecular weight polymer, PVP K90, was more effective in inhibiting the A* --> A transition as compared to PVP K17. The disappearance of M, and the formation of A* and A was simultaneously monitored by XRD. An increase in the drying temperature from 45 to 55 degrees C accelerated the A* --> A transition. In granules prepared by the high-shear process, approximately 50% of theophylline existed as A and the rest as A*. In contrast, the fluid-bed granulation process yielded granules containing only A. Thus, the physical form of theophylline in tablets was influenced by the molecular weight of the binding agent, the granulation method, and the drying temperature. Using A as the starting material, tablets were manufactured by high-shear aqueous wet granulation process and the A* content was quantified. These tablets were stored under various relative humidity (RH) conditions at 25 degrees C for 2 weeks. Storage at RH >or= 33% caused complete A* --> A conversion accompanied by a pronounced decrease in the initial dissolution rate indicating that phase transitions during processing and storage can have a significant influence on product performance.