Quantitative Determination Of Amorphous And Crystalline Drug In Polymer Microspheres

By Leonard C. Thomas, TA Instruments

Biodegradable polymer microspheres, sized 50–200 μm, offer advanced drug delivery by enabling controlled release via injection or inhalation. Factors like particle size, drug distribution, and crystalline structure influence release rates. Thermal analysis methods—Differential Scanning Calorimetry (DSC), Modulated DSC (MDSC), and Thermogravimetry (TGA)—are essential for characterizing these microspheres.

DSC and MDSC analyze crystalline and amorphous drug transitions. Polymorphic transformations are observed during heating, where lower rates reveal multiple melting peaks, and faster rates simplify transitions. In one study, DSC identified 13% crystalline drug in microspheres through melting peak analysis, validated by heat capacity changes during glass transitions in subsequent heating cycles.

TGA complements these techniques by quantifying total drug content. By comparing weight loss rates of placebo and drug-loaded microspheres, TGA measures crystalline monohydrate content from water evolution and total drug content from weight loss at high temperatures. The analysis found microspheres containing 30% total drug, with 13% crystalline and 17% amorphous fractions.

Together, DSC, MDSC, and TGA offer comprehensive insights into microsphere properties, supporting precise drug release system design. This understanding ensures effective delivery, reducing inefficiencies and enhancing therapeutic outcomes, making polymer microspheres a promising platform for controlled drug delivery systems.