Isreb Abdullah, Alhnan Mohamed A, Mkia Abdulrahman, Al-Jammal Khaled, Yaghi Abdallah M, Oga Enoche Florence, Timmins Peter, Bonner Michael, Forbes Robert T
Department of Clinical Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
Department of Life Science and Medicine, Kings College University, London SE1 9NH, UK.
Methods Protoc. 2025 Jan 6;8(1):4. doi: 10.3390/mps8010004.
Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system. This work studies the interaction between model drug combinations (two of ibuprofen, malonic acid, flurbiprofen, or naproxen) dispersed in a polymeric matrix of hypromellose acetate succinate (HPMCAS) using a solvent evaporation technique. Hildebrand and Hansen calculations were used to predict the miscibility of compounds as long as the difference in their solubility parameter values was not greater than 7 MPa. It was observed that the selected APIs (malonic acid, ibuprofen, naproxen, and flurbiprofen) were miscible within the formed polymeric matrix. Adding the API caused depression in the Tg of the polymer to certain concentrations (17%, 23%, 13%) for polymeric matrices loaded with malonic acid, ibuprofen, and naproxen, respectively. Above this, large crystals started to form, and phase separation was seen. Adding two APIs to the same matrix resulted in reducing the saturation concentration of one of the APIs. A trend was observed and linked to Hildebrand and Hansen solubility parameters (HSP).
多药物递送系统已越来越受到制药行业的关注。与此同时，无定形固体分散体作为一种实现生物利用度受溶解度限制的化合物有效口服递送的方法也备受关注。尽管如此，关于预测两种或更多种（无定形形式）药物在聚合物载体中的行为，以及化合物之间、每种化合物与聚合物之间的分子相互作用是否对系统的物理性质有任何影响的信息仍然有限。这项工作使用溶剂蒸发技术研究了分散在醋酸羟丙甲纤维素琥珀酸酯（HPMCAS）聚合物基质中的模型药物组合（布洛芬、丙二酸、氟比洛芬或萘普生中的两种）之间的相互作用。只要化合物的溶解度参数值差异不大于7 MPa，就使用希尔德布兰德和汉森计算来预测化合物的混溶性。观察到所选的活性药物成分（丙二酸、布洛芬、萘普生和氟比洛芬）在形成的聚合物基质中是可混溶的。对于分别负载丙二酸、布洛芬和萘普生的聚合物基质，添加活性药物成分会使聚合物的玻璃化转变温度在一定浓度（17%、23%、13%）下降低。超过此浓度，开始形成大晶体，并出现相分离。向同一基质中添加两种活性药物成分会导致其中一种活性药物成分的饱和浓度降低。观察到一种趋势，并将其与希尔德布兰德和汉森溶解度参数（HSP）联系起来。
