Honick Moshe, Das Sharmila, Hoag Stephen W, Muller Francis X, Alayoubi Alaadin, Feng Xin, Zidan Ahmed, Ashraf Muhammad, Polli James E
University of Maryland, Department of Pharmaceutical Sciences, 20 Penn Street, Baltimore, MD 21201, USA.
Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE 19803 USA.
Eur J Pharm Sci. 2020 Dec 1;155:105556. doi: 10.1016/j.ejps.2020.105556. Epub 2020 Sep 16.
Spray dried dispersions (SDDs) have the potential to dramatically improve the oral bioavailability of drugs with poor water solubility. However, SDDs tend to have material attributes, such as small particle size, low bulk density, and poor flowability, which are undesirable for downstream processing such as tableting. The objective was to perform a comprehensive compaction characterization of both physical mixtures and SDDs consisting of itraconazole (ITZ) and hypromellose acetate succinate (HPMCAS) to elucidate process and material influences on compressibility and compactibility. We fabricated SDDs with 20% ITZ as a model BCS Class 2 drug and 80% HPMCAS as a polymer carrier. Results indicate that SDDs, as well physical mixtures of ITZ and HPMCAS, were easily deformable with similar compressibility profiles across all compression speeds. Analysis of Heckel plots revealed that yield pressures were fairly low for both physical mixtures and SDDs (43.97-59.75 MPa), indicative of ductile materials. SDDs had a much greater propensity to laminate, especially at higher compression speeds, compared to physical mixtures. This difference is likely due to the higher elastic recovery of SDDs. However, for intact tablets, the mechanical strength of compacts from SDDs tended to be higher than those produced from physical mixtures, likely due to the much smaller particle size of the SDDs. Importantly, examination of the compacts with differential scanning calorimetry did not detect any drug crystallization as a result of compaction. In conclusion, while spray drying did not significantly alter the compressibility of binary mixtures ITZ and HPMCAS, it dramatically impacted compactibility and tabletability, increasing elastic recovery, and making the mixtures more prone to lamination. However, at low compression speeds, SDDs produced tablets with higher tensile strength than physical mixtures.
喷雾干燥分散体（SDDs）有潜力显著提高水溶解度差的药物的口服生物利用度。然而，SDDs往往具有一些材料特性，如粒径小、堆密度低和流动性差，这些特性对于压片等下游加工来说是不理想的。目的是对由伊曲康唑（ITZ）和醋酸羟丙甲纤维素琥珀酸酯（HPMCAS）组成的物理混合物和SDDs进行全面的压实特性研究，以阐明工艺和材料对可压缩性和成型性的影响。我们制备了含20% ITZ作为BCS 2类模型药物和80% HPMCAS作为聚合物载体的SDDs。结果表明，SDDs以及ITZ和HPMCAS的物理混合物在所有压缩速度下都易于变形，具有相似的可压缩性曲线。Heckel图分析表明，物理混合物和SDDs的屈服压力都相当低（43.97 - 59.75 MPa），表明材料具有延展性。与物理混合物相比，SDDs更倾向于分层，尤其是在较高的压缩速度下。这种差异可能是由于SDDs的弹性恢复较高。然而，对于完整片剂，由SDDs制成的压片的机械强度往往高于由物理混合物制成的压片，这可能是由于SDDs的粒径小得多。重要的是，用差示扫描量热法检查压片未检测到因压实导致的任何药物结晶。总之，虽然喷雾干燥没有显著改变ITZ和HPMCAS二元混合物的可压缩性，但它对成型性和可压片性有显著影响，增加了弹性恢复，并使混合物更容易分层。然而，在低压缩速度下，SDDs制成的片剂的抗张强度高于物理混合物。
