邱世轩，严 珅，张盛宇，吴 铎

苏州大学 材料与化学化工学部 先进粉体技术工程研究中心，江苏 苏州 215123

引用格式：

邱世轩，严珅，张盛宇，等. 基于表面能量特性的喷雾干燥微粒构效关系［J］. 中国粉体技术，2025，31（6）：1-12.

QIU Shixuan， YAN Shen， ZHANG Shengyu， et al. Structure-property relationship of spray-dried microparticles based on surface energetics［J］. China Powder Science and Technology，2025，31（6）：1−12.

DOI：10.13732/j.issn.1008-5548.2025.06.013

收稿日期：2024-09-24，修回日期：2025-07-04，上线日期：2025-09-28。

基金项目：国家自然科学基金项目，编号：22278284。

第一作者简介：邱世轩（1999—），男，硕士生，研究方向为颗粒技术。E-mail：20215209008@stu. suda. edu. cn。

通信作者简介：吴铎（1981—），男，教授，博士，江苏省“双创博士”引进人才，研究方向为吸入药物粉体制剂研发，干细胞体外三维培养微载体创制，废水深度处理催化剂材料及装备研发，新型喷雾制粒装备设计与工艺优化。E-mail：duo. wu@suda. edu. cn。

摘要：【目的】为了实现微粒流动性的精准调控，探讨基于表面能量特性的喷雾干燥微粒构效关系。【方法】通过调整硬脂酸钠和甘露醇的质量分数，采用喷雾干燥技术制备5组甘露醇-硬脂酸钠微粒样品；利用扫描电子显微镜、X射线衍射仪和X射线光电子能谱仪表征微粒的结构属性，使用反气相色谱仪表征微粒的表面能量特性；通过计算卡尔指数对微粒的流动性进行分析。【结果】加入硬脂酸钠不会显著改变喷雾干燥微粒的形貌和尺寸，但能改变液滴干燥历程，使甘露醇出现亚稳态的δ晶型；硬脂酸钠在微粒表面富集，能够提高微粒的色散表面能但会降低微粒的表面极性，增大微粒表面分子粗糙度，从而改善微粒的流动性。【结论】表面能量特性有助于理解喷雾干燥微粒结构及微粒性能间的关联关系，指导功能性微粒的设计。

关键词：甘露醇；硬脂酸钠；喷雾干燥；反气相色谱；表面能量特性

Abstract

Objective Spray drying technology offers the advantage of one-step formation, enabling the efficient preparation of functional microparticles. It is widely used in the food, chemical, and pharmaceutical industries. However, during the drying process，solvent evaporation within droplets causes solute migration and rearrangement, resulting in dried microparticles with complex surface structures and surface compositions that are difficult to quantify. Furthermore, the morphology, size, and crystal forms of the microparticles can all influence their performance. In this study, inverse gas chromatography (IGC) was employed to characterize the surface properties of the microparticles, exploring the relationship between surface composition and surface energetics, and further analyzing the flowability of the microparticles. The study focuses on elucidating the structure-property relationship between surface composition and particle performance, providing guidance for the design of functional microparticles and enabling precise control of their flowability.

Methods Mannitol and sodium stearate were used as model substances. The feed liquid for spray drying was prepared using high-shear stirring, ultrasonic treatment, and microfluidic homogenization. A series of mannitol‒sodium stearate microparticles was then prepared via spray drying at an inlet temperature of 120 °C. The particle morphology was characterized using scanning electron microscopy (SEM), particle size was measured by laser diffraction, crystal form was analyzed using X-ray diffraction (XRD), and the chemical state of carbon on particle surfaces was examined using X-ray photoelectron spectroscopy (XPS). The surface properties of the microparticles were characterized using IGC at infinite dilution conditions: n-heptane, n-octane，and n-nonane were used to measure the dispersive surface energy; iso-octane was used to determine the surface roughness at the molecular level; and ethyl acetate and isopropanol were used to measure the surface reaction energy. In addition, the flowability of the samples was evaluated by measuring bulk density (Carr’s index).

Results and Discussion After spray drying, the resulting microparticles all exhibited a spherical morphology, and their dispersibility improved slightly with increasing sodium stearate content. However, the sodium stearate content had no significant effect on particle morphology or size. XRD results revealed that the addition of sodium stearate disrupted the formation of mannitol’s ordered crystalline structure, resulting in the precipitation of metastable δ-polymorph. XPS results showed that as the sodium stearate content increased, its proportion on the particle surface also increased. This was mainly due to the surface activity and larger molecular size of sodium stearate, causing it to aggregate on the particle surface during drying. IGC results showed that adding sodium stearate increased the dispersive surface energy of the microparticles, but decreased their surface polarity. When the sodium stearate content was 10% w/w, the dispersive surface energy of the particles reached 65. 1 mJ/m², and the surface reaction energy measured using isopropanol as a probe was 11. 42 kJ/mol. Moreover, the addition of sodium stearate disrupted the orderly arrangement of mannitol molecules on the particle surface, resulting in a more complex molecular arrangement. Accordingly, the surface roughness index measured with iso-octane as a probe decreased with increasing sodium stearate content. The flowability of the samples improved significantly with higher sodium stearate content: the Carr’s index of the spray-dried pure mannitol sample was as high as 48. 56%, but decreased to 29. 7% when the sodium stearate content was 10% w/w, which was due to the hydrophobic shell formed by sodium stearate enrichment on the particle surface.

Conclusion The IGC technology provides new insights into the surface properties of spray-dried microparticles. The addition of sodium stearate promotes the formation of a hydrophobic surface on the spray-dried microparticles, enhances the dispersive surface forces, and reduces the surface reaction energy, making the sample less prone to absorbing water during collection, transfer, and storage, and ultimately improving their flowability.

Keywords：mannitol; sodium stearate; spray drying; inverse gas chromatography; surface energetics

参考文献（References）

［1］PIÑÓN-BALDERRAMA C I, LEYVA-PORRAS C, TERÁN-FIGUEROA Y, et al. Encapsulation of active ingredients in food industry by spray-drying and nano spray-drying technologies［J］. Processes，2020，8（8）：889-916.

［2］ZIAEE A, ALBADARIN A B, PADRELA L, et al. Spray drying of pharmaceuticals and biopharmaceuticals: critical parameters and experimental process optimization approaches［J］. European Journal of Pharmaceutical Sciences，2019，127：300-318.

［3］HO R, NADERI M, HENG J Y Y, et al. Effect of milling on particle shape and surface energy heterogeneity of needle-shaped crystals［J］. Pharmaceutical Research，2012，29（10）：2806-2816.

［4］YU J Q, ROMEO M C, CAVALLARO A A, et al. Protective effect of sodium stearate on the moisture-induced deterioration of hygroscopic spray-dried powders［J］. International Journal of Pharmaceutics，2018，541（1/2）：11-18.

［5］JIANG T T, YAN S, ZHANG S Y, et al. Uniform lactose microspheres with high crystallinity fabricated by micro-fluidic spray drying technology combined with post-treatment process［J］. Powder Technology，2021，392：690-702.

［7］BOEL E, KOEKOEKX R, DEDROOG S, et al. Unraveling particle formation: from single droplet drying to spray drying and electrospraying［J］. Pharmaceutics，2020，12（7）：625-683.

［8］MANGAL S, PARK H, NOUR R, et al. Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants［J］. International Journal of Pharmaceutics，2019，568：118504.

［9］SHETTY N, PARK H, ZEMLYANOV D, et al. Influence of excipients on physical and aerosolization stability of spray dried high-dose powder formulations for inhalation［J］. International Journal of Pharmaceutics，2018，544（1）：222-234.

［10］WANG B Y, WANG X L, ZHU Y J, et al. Characterization of nimodipine amorphous nanopowder prepared by quenching cooling combined with wet milling and spray drying［J］. International Journal of Pharmaceutics，2022，628：122332.

［11］YOUNG P M, COCCONI D, COLOMBO P, et al. Characterization of a surface modified dry powder inhalation carrier prepared by “particle smoothing”［J］. Journal of Pharmacy and Pharmacology，2010，54（10）：1339-1344.

［12］TORGE A, GRÜTZMACHER P, MÜCKLICH F, et al. The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles［J］. European Journal of Pharmaceutical Sciences，2017，104：171-179.

［13］ALGHUNAIM A, KIRDPONPATTARA S, NEWBY B Z. Techniques for determining contact angle and wettability of powders［J］. Powder Technology，2016，287：201-215.

［14］KUNG C H, SOW P K, ZAHIRI B, et al. Assessment and interpretation of surface wettability based on sessile droplet contact angle measurement: challenges and opportunities［J］. Advanced Materials Interfaces，2019，6（18）：1900839.

［15］LA Z D, ZHANG F W, SUN F L, et al. Drug powders with tunable wettability by atomic and molecular layer deposition: from highly hydrophilic to superhydrophobic［J］. Applied Materials Today，2021，22：100945.

［16］SALEHI H, KARDE V, HAJMOHAMMADI H, et al. Understanding flow properties of mannitol powder at a range of temperature and humidity［J］. International Journal of Pharmaceutics，2021，596：120244.

［17］BAI W L, PAKDEL E, LI Q X, et al. Inverse gas chromatography (IGC) for studying the cellulosic materials surface characteristics: a mini review［J］. Cellulose，2023，30（6）：3379-3396.

［18］BUNGERT N, KOBLER M, SCHERLIESS R. Surface energy considerations in ternary powder blends for inhalation［J］. International Journal of Pharmaceutics，2021，609：121189.

［19］THOOL P, STANCILL C, BUI M, et al. Evaluation of time consolidation effect of pharmaceutical powders［J］. Pharmaceutical Research，2022，39（12）：3345-3357.

［20］CARES-PACHECO M G, VACA-MEDINA G, CALVET R, et al. Physicochemical characterization of d-mannitol polymorphs: the challenging surface energy determination by inverse gas chromatography in the infinite dilution region［J］. International Journal of Pharmaceutics，2014，475（1/2）：69-81.

［21］ALHAJJ N, O’REILLY N J, CATHCART H. Designing enhanced spray dried particles for inhalation: a review of the impact of excipients and processing parameters on particle properties［J］. Powder Technology，2021，384：313-331.

［22］MA X Q, YAN S, ZHANG S Y, et al. Shell-formation mediated surface composition of uniform two-component microparticles fabricated by micro-fluidic spray drying： effect of component size and solubility［J］. Particuology，2022，67：68-78.

［23］YANG Y X, LIU J, HU A N, et al. A critical review on engineering of d-mannitol crystals: properties, applications， and polymorphic control［J］. Crystals，2022，12（8）：1080.

［24］QI Y L, CHEN T T, ZHANG J. A facile method of hydrophobic surface modification for acrylonitrile-styrene-acrylateterpolymer based on the out-migration property of metallic soaps［J］. Applied Surface Science，2018，435：503-511.

［25］ENFERAD S, PETIT J, GAIANI C, et al. Effect of particle size and formulation on powder rheology［J］. Particulate Science and Technology，2021，39（3）：362-370.