Granados Pedro A, Gross Idejan P, Medeiros-Souza Patrícia, Sá-Barreto Livia L, Gelfuso Guilherme M, Gratieri Tais, Cunha-Filho Marcilio
Laboratory of Food, Drug, and Cosmetics (LTMAC), University of Brasilia, Brasilia 70910-900, DF, Brazil.
Department of Pharmacy, University of Brasília, Brasília 72220-900, DF, Brazil.
Pharmaceutics. 2025 Apr 29;17(5):586. doi: 10.3390/pharmaceutics17050586.
: Triamcinolone acetonide (TA), a poorly water-soluble corticosteroid, presents formulation challenges due to limited membrane permeability. This study aimed to identify suitable drug-polymer-plasticizer systems for TA using combined theoretical and experimental methods. : Using Hansen solubility parameters, seven hot-melt extrusion (HME)-grade polymers and four plasticizers were initially screened for miscibility with TA. Based on Δδt values, four polymers-Eudragit L100 (EUD), Parteck MXP (PVA), Plasdone S-630 (PVPVA), and Aquasolve™ AS-MG (HPMCAS)-along with triethyl citrate (TEC), were selected for experimental evaluation. Differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy assessed thermal behavior, miscibility, and chemical compatibility. : Amorphous TA content was highest with EUD (81.1%), followed by PVA (67.5%), PVPVA (45.6%), and HPMCAS (8.5%). Thermal incompatibility and TEC evaporation were observed in PVA, PVPVA, and HPMCAS systems. FTIR suggested TEC should be avoided in melt-based formulations with PVA and PVPVA due to PVA degradation and partial TA oxidation. No significant interactions were detected in HPMCAS samples heated to 220 °C, aligning with theoretical predictions. In contrast, the EUD-TEC system showed limited chemical reactivity and maintained TA's structural integrity. Infrared bands at 1758 and 1802 cm indicated minor anhydride formation above 160 °C with partial TEC evaporation. : EUD/TEC were identified as a promising combination for the HME processing of TA. This work supports the rational formulation of stable amorphous systems for thermolabile drugs with poor solubility.
曲安奈德（TA）是一种水溶性较差的皮质类固醇，由于膜通透性有限，在制剂方面存在挑战。本研究旨在通过理论和实验相结合的方法，确定适合TA的药物-聚合物-增塑剂体系。：利用汉森溶解度参数，初步筛选了七种热熔挤出（HME）级聚合物和四种增塑剂与TA的混溶性。基于Δδt值，选择了四种聚合物——丙烯酸树脂L100（EUD）、聚维酮MXP（PVA）、聚维酮S-630（PVPVA）和Aquasolve™ AS-MG（HPMCAS）——以及柠檬酸三乙酯（TEC）进行实验评估。差示扫描量热法、热重分析和傅里叶变换红外光谱法评估了热行为、混溶性和化学相容性。：EUD的无定形TA含量最高（81.1%），其次是PVA（67.5%）、PVPVA（45.6%）和HPMCAS（8.5%）。在PVA、PVPVA和HPMCAS体系中观察到热不相容性和TEC蒸发。FTIR表明，由于PVA降解和部分TA氧化，在基于熔体的PVA和PVPVA制剂中应避免使用TEC。在加热到220°C的HPMCAS样品中未检测到明显的相互作用，这与理论预测一致。相比之下，EUD-TEC体系显示出有限的化学反应性，并保持了TA的结构完整性。1758和1802 cm处的红外波段表明，在160°C以上有少量酸酐形成，同时有部分TEC蒸发。：EUD/TEC被确定为TA热熔挤出加工的有前景的组合。这项工作支持了针对溶解度差的热不稳定药物合理配制稳定的无定形体系。
