Calcium phosphates in pharmaceutical tableting. 1. Physico-pharmaceutical properties

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Calcium phosphates are widely used excipients in direct tableting formulations.
• Understanding their physical and chemical properties is crucial for successful drug product development.

Purpose of the Study:

• To evaluate ten commercial calcium phosphates for direct tableting.
• To compare their particle size, powder properties, water sorption, and pH.

Main Methods:

• Characterization of particle size distribution and powder flowability.
• Sorption isotherm analysis at 93% relative humidity.
• pH measurement of aqueous slurries.
• Scanning electron microscopy (SEM) for manufacturing insights.

Main Results:

• All calcium phosphates exhibited sufficient flowability for tableting.
• Manufacturing methods significantly impacted water sorption, with hydroxylapatites showing high moisture uptake (>15%) and dibasic calcium phosphate dihydrate being non-hygroscopic (<1%).
• Monobasic calcium phosphate monohydrate demonstrated acidic properties, while others were near neutral.

Conclusions:

• Calcium phosphate properties, especially water sorption, vary significantly with manufacturing processes.
• The presence of crystal water in some calcium phosphates may lead to problematic interactions with active pharmaceutical ingredients.
• Selection of appropriate calcium phosphate excipients requires careful consideration of their specific properties and intended use.