Macromolecules Innovation Institute, Department of Sustainable Biomaterials, College of Natural Resources and Environment, Virginia Tech, Blacksburg, Virginia 24061, United States.
Department of Chemistry, University of the West Indies, Mona, Kingston JMAAW15, Jamaica.
Mol Pharm. 2024 Sep 2;21(9):4589-4602. doi: 10.1021/acs.molpharmaceut.4c00493. Epub 2024 Aug 1.
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 () 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 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.
无定形固体分散体（ASD）在聚合物基质中是一种提高溶解性和生物利用度的有效方法，适用于原本结晶、水溶性差的药物。醋酸丁酸纤维素（CCAB）是一种相对较新的商业纤维素衍生物，用于水基涂料应用。由于 CCAB 是一种具有两亲性、含羧基、玻璃化转变温度（Tg）高的聚合物，具有形成优秀 ASD 聚合物的关键特性，因此我们选择探索其 ASD 潜力。我们将结构多样的药物槲皮素、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 形成与这些药物的 ASD 的能力及其提供增溶和有效药物释放的能力。通过喷雾干燥制备的 CCAB/药物分散体在高达 25wt%药物的情况下为非晶态，而氯雷他定在高达 50wt%药物的情况下仍为非晶态。含有 10wt%药物的 CCAB 制剂有效地提高了结晶黄酮类药物槲皮素和利托那韦的溶解度，但对更易溶的 API 布洛芬和克拉霉素以及疏水性更强的氯雷他定没有效果。CCAB 确实提供了布洛芬的缓慢和控制释放，提供了一种简单而有前途的长效布洛芬制剂。含有克拉霉素的制剂表现出聚合物在胃 pH 下保护药物免受降解的能力。此外，加入水溶性聚合物聚乙烯吡咯烷酮（PVP）可以改善 CCAB 与氯雷他定和布洛芬的 ASD，CCAB 与 PVP 具有良好的混溶性。CCAB 在某些情况下提高了溶解度，CCAB 表现出的较慢的药物释放，尤其是在胃中，可能特别有益，例如，在含有已知的胃刺激性药物如布洛芬的制剂中。
