engleski

Mechanisms of polymer matrix formation in a sustained release tablet studied by DMA and DSC

Poly(ethyl acrylate, methyl methacrylate, 2:1) [poly(EA-MMA)] matrix tablets containing diclofenac sodium (DS) were studied by dynamic mechanical analyses (DMA) and differential scanning calorimetry (DSC) to understand the mechanisms of matrix formation. DS was granulated with an aqueous dispersion of poly(EA-MMA) (MFT=5°C, Tg=(-8)°C) at 15:1 and 3:1 mass ratios. Duplicate batches were dried at 4°C. Half of the granules were cured at 50°C for 1 h. All granules were compressed at 7.5t or 15t loading. Portions of the compacts were examined by DMA (TA Instruments, DMA 983) and DSC (Perkin Elmer, DSC Pyris 1). Flex storage modulus E` was lower and non-uniform for the low polymer content systems (LPS). It increased upon higher compression load, independently of formulation or granule treatment. Flex loss modulus E`` was characterised by two peaks. The first peak appeared around (-30)± 5°C in the LPS and was related to DS. The second, poly(EA-MMA), peak, appeared in the range (36-45)°C for the LPS and (24-30)°C for the HPS, and was not markedly influenced by either granule treatment or compression load. Although the Tg of the polymer is (-8)°C, the DMA suggests that glass to rubber transition occurs at much higher temperatures in the matrix. Preliminary DSC showed corresponding endothermic transitions. Matrix stiffness (indicated by E`) increased upon increased compression loading, while the Tgs of the poly(EA-MMA) matrices (indicated by E`) were primarily influenced by formulation and were much higher than that of polymer alone. Consequently, changes could occur in matrices during processing and on storage and this could affect drug release characteristics.

Poly(EA-MMA); matrix formation; DMA; DSC; glass transition

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