Laboratorium voor Farmacotechnologie en Biofarmacie, K.U. Leuven, Herestraat 49, Leuven, Belgium.
Eur J Pharm Biopharm. 2012 May;81(1):207-13. doi: 10.1016/j.ejpb.2012.01.007. Epub 2012 Jan 24.
The aim of this work is to investigate the effect of compression on miscibility of naproxen (NAP)-PVP K25 solid dispersions. Solid dispersions with diverse drug/polymer compositions were compressed at various forces for uniform dwell time. Miscibility assessments were performed using mDSC, and the effect of compression on the specific interactions of NAP and PVP K25 was investigated by FTIR. The 20% (w/w) naproxen containing solid dispersion showed a single T(g) before and after compression. FTIR analysis showed the unchanged profile of this system upon compression. On the other hand, the miscibility in the compositions with 30% and 40% (w/w) naproxen is markedly affected by compression. Compression pressures from beyond 565.05 MPa induced apparent amorphous-amorphous phase separation as indicated by two characteristic T(g)s in DSC and altered IR spectral profile. The highly ductile nature of PVP promotes plastic deformation upon compression induced by the rotation of the PVP backbone with the transition of dihedral angles from low to high energy state. Segmental rotation can also be an outcome of plastic deformation that often leads to increase in structural temperature. This can have influence on miscibility resulting from weakening and/or disruption of intermolecular hydrogen bonding between drug and polymer upon compression.
本工作旨在研究压缩对萘普生（NAP）-PVP K25 固体分散体混溶性的影响。将具有不同药物/聚合物组成的固体分散体在不同的压力下压缩，以达到均匀的停留时间。使用 mDSC 进行混溶性评估，并通过 FTIR 研究压缩对 NAP 和 PVP K25 特定相互作用的影响。在压缩前后，含有 20%（w/w）萘普生的固体分散体显示出单个 T(g)。FTIR 分析表明该体系在压缩后其谱图没有变化。另一方面，30%和 40%（w/w）萘普生组成的混溶性明显受到压缩的影响。超过 565.05 MPa 的压缩压力会导致明显的无定形-无定形相分离，这表现在 DSC 中有两个特征 T(g)和改变的 IR 光谱谱图。PVP 的高延展性促进了在 PVP 主链旋转时发生的塑性变形，伴随着二面角从低能量状态到高能量状态的转变。片段旋转也可能是塑性变形的结果，这通常会导致药物和聚合物之间的分子间氢键变弱和/或破坏，从而影响混溶性。
