Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
AAPS PharmSciTech. 2023 Sep 22;24(7):193. doi: 10.1208/s12249-023-02644-2.
Previously, we have shown that thin-film freeze-drying can be applied to prepare dry powders of bacteria such as Lactobacillus acidophilus. Herein, we tested the viability of L. acidophilus in thin-film freeze-dried powders (TFF powders) filled in delayed-release vegetarian capsules in a simulated gastric fluid (SGF) consisting of 0.1N hydrochloric acid and sodium chloride. Initially, we determined the water removal rate from frozen thin films on relatively larger scales (i.e., 10-750 g). We then prepared and characterized two TFF powders of L. acidophilus with either sucrose and maltodextrin or sucrose and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), a pH-sensitive polymer, as excipients and evaluated the viability of the bacteria after the TFF powders were filled in delayed-release vegetarian capsules and the capsules were incubated in the SGF for 30 min. On 10-750 g scales and at the settings specified, water removal from frozen thin films was faster than from slow shelf-frozen bulk solids. When the L. acidophilus in sucrose and HPMC-AS TFF powder was filled into a delayed-release capsule that was placed into another delayed-release capsule, the bacterial viability reduction after incubation in the SGF can be minimized to within 1 log in colony forming unit (CFU). However, for the L. acidophilus in sucrose and maltodextrin TFF powder, even in the capsule-in-capsule dosage form, bacterial CFU reduction was > 2 logs. TFF powders of live microorganisms containing an acid-resistant material in capsule-in-capsule delayed-release vegetarian capsules have the potential for oral delivery of those microorganisms.
先前，我们已经证明，薄膜冷冻干燥可用于制备嗜酸乳杆菌等细菌的干粉。在此，我们测试了填充在延迟释放素食胶囊中的嗜酸乳杆菌薄膜冷冻干燥粉末（TFF 粉末）在模拟胃液（SGF）中的生存能力，SGF 由 0.1N 盐酸和氯化钠组成。最初，我们在相对较大的规模（即 10-750g）上确定了从冷冻薄膜中去除水分的速率。然后，我们制备并表征了两种嗜酸乳杆菌 TFF 粉末，一种使用蔗糖和麦芽糊精，另一种使用蔗糖和羟丙基甲基纤维素醋酸琥珀酸酯（HPMC-AS）作为赋形剂，HPMC-AS 是一种 pH 敏感聚合物，并评估了填充在延迟释放素食胶囊中的 TFF 粉末和胶囊在 SGF 中孵育 30 分钟后的细菌活力。在 10-750g 规模和指定的条件下，冷冻薄膜的水分去除速度比缓慢货架冷冻的块状固体快。当在蔗糖和 HPMC-AS TFF 粉末中的嗜酸乳杆菌填充到延迟释放胶囊中，然后将胶囊放入另一个延迟释放胶囊中时，在 SGF 中孵育后的细菌生存能力降低可以最小化到 1 个对数形成单位（CFU）以内。然而，对于在蔗糖和麦芽糊精 TFF 粉末中的嗜酸乳杆菌，即使在胶囊套胶囊剂型中，细菌 CFU 减少>2 个对数。含有耐酸材料的活微生物的 TFF 粉末在胶囊套胶囊延迟释放素食胶囊中具有口服递送这些微生物的潜力。
