当前位置：
X-MOL 学术
›
Cryst. Growth Des.
›
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.)
Influence of Excipients on Cocrystal Stability and Formation
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2020-05-26 , DOI: 10.1021/acs.cgd.0c00321 Marwah Aljohani 1 , Patrick McArdle 1, 2 , Andrea Erxleben 1, 2
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2020-05-26 , DOI: 10.1021/acs.cgd.0c00321 Marwah Aljohani 1 , Patrick McArdle 1, 2 , Andrea Erxleben 1, 2
Affiliation
|
Cocrystal formation is widely used to modify and optimize the physicochemical properties of an active pharmaceutical ingredient (API). However, the stability of cocrystals toward formulation with excipients is little investigated. In this work, the effect of grinding in the presence of the common excipients polyvinylpyrrolidone (PVP) and microcrystalline cellulose (MCC) on 11 cocrystals and a salt of the sulfonamide diuretic chlorothiazide (ctz) was studied (ctz-bipy, ctz-ebipy, ctz-pbipy, ctz-pyr, ctz-hyp, ctz-hma, ctz-bza, ctz-nia, ctz-ina, ctz-cbz, ctz-aca, ctz-ppa, (bzamH+)(ctz–); bipy = 4,4′-bipyridine, ebipy = 1,2-di(4-pyridyl)ethylene, pbipy = 1,3-di(4-pyridyl)propane, pyr = pyrazine, hyp = 2-hydroxypyridine, hma = hexamethylenetetramine, bza = benzamide, nia = nicotinamide, ina = isonicotinamide, cbz = carbamazepine, aca = acetamide, ppa = propionamide, bzamH+ = benzamidinium). Except for ctz-ppa and ctz-aca, all cocrystals were stable toward milling with 1 weight equiv PVP or MCC. It was also shown that the cocrystals ctz-bipy, ctz-ebipy, ctz-pbipy, ctz-pyr, ctz-hma, ctz-bza, ctz-ina, ctz-cbz, and the salt (bzamH+)(ctz–) formed in situ, when ctz was milled with the respective coformer in the presence of PVP or MCC. The stability and formation of ctz-cbz, ctz-nia, and htz-nia (htz = hydrochlorothiazide) toward grinding with a wider range of excipients (HPC, α-lactose, deoxycholic acid, and sodium taurocholate) was also investigated, and the results are discussed with regard to the heterosynthons of the ctz cocrystals and competing H bonding with the excipients.
中文翻译：
赋形剂对共晶稳定性和形成的影响
共晶形成被广泛用于修饰和优化活性药物成分（API）的物理化学性质。然而，很少研究共晶对赋形剂配制的稳定性。在这项工作中，研究了在常见赋形剂聚乙烯吡咯烷酮（PVP）和微晶纤维素（MCC）存在下研磨对11种共晶体和磺酰胺利尿剂氯噻嗪（ctz）盐的影响（ctz-bipy，ctz-ebipy， ctz-pbipy，ctz-pyr，ctz-hyp，ctz-hma，ctz-bza，ctz-nia，ctz-ina，ctz-cbz，ctz-aca，ctz-ppa，（bzamH +）（ctz –）; bipy = 4,4'-联吡啶，ebipy = 1,2-二（4-吡啶基）乙烯，pbipy = 1,3-二（4-吡啶基）丙烷，pyr =吡嗪，hyp = 2-羟基吡啶，hma =六亚甲基四胺，bza =苯甲酰胺，nia =烟酰胺，ina =异烟酰胺，cbz =卡马西平，aca =乙酰胺，ppa =丙酰胺，bzamH + =苯甲din鎓。除ctz-ppa和ctz-aca以外，所有共结晶均对1重量当量的PVP或MCC稳定。还显示了共晶体ctz-bipy，ctz-ebipy，ctz-pbipy，ctz-pyr，ctz-hma，ctz-bza，ctz-ina，ctz-cbz和盐（bzamH +）（ctz –）原位形成，当在PVP或MCC存在下将ctz与相应的共成型机一起研磨时。还研究了ctz-cbz，ctz-nia和htz-nia（htz =氢氯噻嗪）对更广泛的赋形剂（HPC，α-乳糖，脱氧胆酸和牛磺胆酸钠）研磨的稳定性和形成，并且讨论了关于ctz共晶体的杂合子以及与赋形剂竞争H键的结果。
更新日期：2020-07-01
中文翻译：
赋形剂对共晶稳定性和形成的影响
共晶形成被广泛用于修饰和优化活性药物成分（API）的物理化学性质。然而，很少研究共晶对赋形剂配制的稳定性。在这项工作中，研究了在常见赋形剂聚乙烯吡咯烷酮（PVP）和微晶纤维素（MCC）存在下研磨对11种共晶体和磺酰胺利尿剂氯噻嗪（ctz）盐的影响（ctz-bipy，ctz-ebipy， ctz-pbipy，ctz-pyr，ctz-hyp，ctz-hma，ctz-bza，ctz-nia，ctz-ina，ctz-cbz，ctz-aca，ctz-ppa，（bzamH +）（ctz –）; bipy = 4,4'-联吡啶，ebipy = 1,2-二（4-吡啶基）乙烯，pbipy = 1,3-二（4-吡啶基）丙烷，pyr =吡嗪，hyp = 2-羟基吡啶，hma =六亚甲基四胺，bza =苯甲酰胺，nia =烟酰胺，ina =异烟酰胺，cbz =卡马西平，aca =乙酰胺，ppa =丙酰胺，bzamH + =苯甲din鎓。除ctz-ppa和ctz-aca以外，所有共结晶均对1重量当量的PVP或MCC稳定。还显示了共晶体ctz-bipy，ctz-ebipy，ctz-pbipy，ctz-pyr，ctz-hma，ctz-bza，ctz-ina，ctz-cbz和盐（bzamH +）（ctz –）原位形成，当在PVP或MCC存在下将ctz与相应的共成型机一起研磨时。还研究了ctz-cbz，ctz-nia和htz-nia（htz =氢氯噻嗪）对更广泛的赋形剂（HPC，α-乳糖，脱氧胆酸和牛磺胆酸钠）研磨的稳定性和形成，并且讨论了关于ctz共晶体的杂合子以及与赋形剂竞争H键的结果。
京公网安备 11010802027423号