当前位置: X-MOL 学术Pharmaceutics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound.
Pharmaceutics ( IF 4.9 ) Pub Date : 2020-05-18 , DOI: 10.3390/pharmaceutics12050460
Justyna Knapik-Kowalczuk 1 , Krzysztof Chmiel 1 , Justyna Pacułt 1 , Klaudia Bialek 2 , Lidia Tajber 2 , Marian Paluch 1
Affiliation  

The main purpose of this paper was to evaluate the impact of both high- and low-Tg polymer additives on the physical stability of an amorphous drug, sildenafil (SIL). The molecular mobility of neat amorphous SIL was strongly affected by the polymeric excipients used (Kollidon VA64 (KVA) and poly(vinylacetate) (PVAc)). The addition of KVA slowed down the molecular dynamics of amorphous SIL (antiplasticizing effect), however, the addition of PVAc accelerated the molecular motions of the neat drug (plasticizing effect). Therefore, in order to properly assess the effect of the polymer on the physical stability of SIL, the amorphous samples at both: isothermal (at constant temperature-353 K) and isochronal (at constant relaxation time-τα = 1.5 ms) conditions were compared. Our studies showed that KVA suppressed the recrystallization of amorphous SIL more efficiently than PVAc. KVA improved the physical stability of the amorphous drug, regardless of the chosen concentration. On the other hand, in the case of PVAc, a low polymer content (i.e., 25 wt.%) destabilized amorphous SIL, when stored at 353 K. Nevertheless, at high concentrations of this excipient (i.e., 75 wt.%), its effect on the amorphous pharmaceutical seemed to be the opposite. Therefore, above a certain concentration, the PVAc presence no longer accelerates the SIL recrystallization process, but inhibits it.

中文翻译:

用增塑或抗增塑化合物增强无定形西地那非在二元混合物中的物理稳定性。

本文的主要目的是评估高Tg和低Tg聚合物添加剂对无定形药物Sildenafil(SIL)物理稳定性的影响。所用的聚合物赋形剂(Kollidon VA64(KVA)和聚(乙酸乙烯酯)(PVAc))对纯净无定形SIL的分子迁移性有很大影响。添加KVA会减慢非晶态SIL的分子动力学(抗塑化作用),但是,添加PVAc会加速纯药物的分子运动(塑化作用)。因此,为了正确评估聚合物对SIL物理稳定性的影响,比较了等温(在353 K恒温下)和等时(在恒定弛豫时间-τα= 1.5 ms)条件下的无定形样品。 。我们的研究表明,KVA比PVAc更有效地抑制了非晶SIL的再结晶。无论选择何种浓度,KVA均可改善无定形药物的物理稳定性。另一方面,在PVAc的情况下,低聚合物含量(即25 wt。%)在353 K下储存时会破坏稳定的非晶态SIL。尽管如此,在高浓度的这种赋形剂(即75 wt。%)下,它对无定形药物的作用似乎相反。因此,高于一定浓度时,PVAc的存在不再加速SIL重结晶过程,而是抑制了它。然而,在高浓度的这种赋形剂(即75重量%)下,其对无定形药物的作用似乎是相反的。因此,高于一定浓度时,PVAc的存在不再加速SIL重结晶过程,而是抑制了它。然而,在高浓度的这种赋形剂(即75重量%)下,其对无定形药物的作用似乎是相反的。因此,高于一定浓度时,PVAc的存在不再加速SIL重结晶过程,而是抑制了它。
更新日期:2020-05-18
down
wechat
bug