Thompson Stephen A, Davis Daniel A, Miller Dave A, Kucera Sandra U, Williams Robert O
Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 W. University Ave, PHR 4.214, Austin, TX 78712, USA.
AustinPx, LLC, 111 W Cooperative Way, Suite 300, Georgetown, TX 78626, USA.
Biomedicines. 2023 Apr 26;11(5):1281. doi: 10.3390/biomedicines11051281.
This study compares the effects of pre-processing multiple polymers together to form a single-phase polymer alloy prior to amorphous solid dispersion formulation. KinetiSol compounding was used to pre-process a 1:1 (/) ratio of hypromellose acetate succinate and povidone to form a single-phase polymer alloy with unique properties. Ivacaftor amorphous solid dispersions comprising either a polymer, an unprocessed polymer blend, or the polymer alloy were processed by KinetiSol and examined for amorphicity, dissolution performance, physical stability, and molecular interactions. A polymer alloy ivacaftor solid dispersion with a drug loading of 50% / was feasible versus 40% for the other compositions. Dissolution in fasted simulated intestinal fluid revealed that the 40% ivacaftor polymer alloy solid dispersion reached a concentration of 595 µg/mL after 6 h, 33% greater than the equivalent polymer blend dispersion. Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance revealed changes in the ability of the povidone contained in the polymer alloy to hydrogen bond with the ivacaftor phenolic moiety, explaining the differences in the dissolution performance. This work demonstrates that the creation of polymer alloys from polymer blends is a promising technique that provides the ability to tailor properties of a polymer alloy to maximize the drug loading, dissolution performance, and stability of an ASD.
本研究比较了在无定形固体分散体制备之前将多种聚合物一起预处理以形成单相聚合物合金的效果。采用KinetiSol共混法对醋酸羟丙甲纤维素琥珀酸酯和聚维酮按1:1（/）的比例进行预处理，以形成具有独特性能的单相聚合物合金。通过KinetiSol制备了包含聚合物、未处理的聚合物共混物或聚合物合金的依伐卡托无定形固体分散体，并对其无定形性、溶解性能、物理稳定性和分子相互作用进行了研究。载药量为50% / 的聚合物合金依伐卡托固体分散体是可行的，而其他组合物的载药量为40%。在禁食模拟肠液中的溶解情况显示，40%的依伐卡托聚合物合金固体分散体在6小时后达到了595 µg/mL的浓度，比同等聚合物共混物分散体高33%。傅里叶变换红外光谱和固态核磁共振显示，聚合物合金中所含聚维酮与依伐卡托酚羟基部分形成氢键的能力发生了变化，这解释了溶解性能的差异。这项工作表明，由聚合物共混物制备聚合物合金是一种很有前景的技术，它能够调整聚合物合金的性能，以最大限度地提高无定形固体分散体的载药量、溶解性能和稳定性。
