Pharmaceutical & Analytical R & D, Hoffmann-La Roche Inc, Nutley, New Jersey, 07110.
J Pharm Sci. 2013 Oct;102(10):3604-13. doi: 10.1002/jps.23661. Epub 2013 Aug 17.
The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd ) were determined along with Hiestand indices using compacts prepared at a solid fraction of ∼0.85. HPMCAS and copovidone exhibited lower Hd , lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId ) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.
研究了熔融挤出（HME）和喷雾干燥（SD）对醋酸琥珀酸羟丙甲纤维素（HPMCAS）、共聚维酮及其配方混合物的机械性能的影响，并将其与参考赋形剂进行了比较。使用约 0.85 固体分数制备的压片测定了拉伸强度（TS）、压缩压力（CP）、弹性模量（E）和动态硬度（Hd）以及 Hiestand 指数。HPMCAS 和共聚维酮的 Hd、CP 和 E 均低于参考赋形剂，且具有中等 TS。根据脆性断裂指数值，发现 HPMCAS 具有高脆性。与未加工材料相比，SD 和 HME 后 HPMCAS 的 CP 分别提高了 24%和 61%，同时 Hd 也更高。此外，HME 后 HPMCAS 和共聚维酮的 TS 降低。当熔融挤出的 HPMCAS 与微晶纤维素等塑性材料混合时，TS 增加。这些结果表明，SD 和 HME 可以通过减少材料的变形来影响返工性，在 HME 的情况下，由于在螺杆挤出机中加热和剪切应力的作用，可能会增加密度。赋形剂和配方混合物的动态结合指数（BId）也观察到了类似的效果。这些数据可用于定量评估加工对片剂配方开发过程中材料机械性能的影响。
