聚合物基质中的无定形固体分散体(ASD)是一种有效的方法,可以增强其他晶体的溶解度和生物利用度,水溶性差的药物。6-纤维素乙酸丁酸酯(CCAB)是相对新的商业纤维素衍生物,其被引入用于水性涂料应用中。由于CCAB是两亲性的,含羧基,高玻璃化转变温度(Tg)聚合物,优异的ASD聚合物性能所必需的特性,我们选择探索其ASD潜力。结构不同的药物槲皮素,布洛芬,利托那韦,氯雷他定,和克拉霉素分散在CCAB基质中。我们评估了CCAB用这些药物产生ASD的能力及其提供溶解度增强和有效药物释放的能力。通过喷雾干燥制备的CCAB/药物分散体是无定形的,高达25重量%的药物,与氯雷他定保持无定形高达50%的药物。具有10%药物的CCAB制剂被证明可有效增强结晶类黄酮药物槲皮素和利托那韦的体外溶解度,但不为更易溶的原料药布洛芬和克拉霉素和更疏水性的氯雷他定。CCAB确实提供了布洛芬的缓慢和受控释放,提供一个简单和有前途的长期布洛芬制剂。含有克拉霉素的制剂显示出聚合物在胃pH下防止药物降解的能力。此外,CCABASD与氯雷他定和布洛芬都可以通过添加水溶性聚合物聚(乙烯基吡咯烷酮)(PVP),与CCAB表现出良好的混溶性。CCAB在某些情况下提供溶解度增强,CCAB表现出较慢的药物释放,尤其是在胃里,可能特别有益,例如,在含有布洛芬等已知胃刺激物的制剂中。
Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature (Tg) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir,
loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with
loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic
loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both
loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.