Erfani Amir, Reichert Paul, Narasimhan Chakravarthy N, Doyle Patrick S
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Merck & Co., Inc., Kenilworth, NJ 07033, USA.
iScience. 2023 Jul 22;26(8):107452. doi: 10.1016/j.isci.2023.107452. eCollection 2023 Aug 18.
The fast pace of breakthroughs in cancer immunotherapy, combined with the new paradigm of moving toward high-concentration dosages and combinatorial treatments, is generating new challenges in the formulation of biologics. To address these challenges, we describe a method of formulation that enables high-concentration injectable and stable formulation of biologics as amorphous solids in aqueous suspension. This technology combines the benefits of liquid formulation with the stability of solid formulation and eliminates the need for drying and reconstitution. This widely applicable formulation integrates the amorphous solid forms of antibodies with the injectability, lubricity, and tunability of soft alginate hydrogel particles using a minimal process. The platform was evaluated for anti-PD-1 antibody pembrolizumab and human immunoglobulin G at concentrations up to 300 mg/mL with confirmed quality after release. The soft nature of the hydrogel matrix allowed packing the particles to high volume fractions.
癌症免疫疗法的快速突破，再加上朝着高浓度剂量和联合治疗发展的新范式，给生物制剂的配方带来了新的挑战。为应对这些挑战，我们描述了一种配方方法，该方法能够将生物制剂以无定形固体的形式在水性悬浮液中制成高浓度可注射且稳定的制剂。这项技术结合了液体制剂的优点和固体制剂的稳定性，无需干燥和重构。这种广泛适用的配方通过一个简单的过程，将抗体的无定形固体形式与柔软的藻酸盐水凝胶颗粒的可注射性、润滑性和可调性结合在一起。该平台针对抗PD - 1抗体帕博利珠单抗和人免疫球蛋白G进行了评估，浓度高达300 mg/mL，释放后质量得到确认。水凝胶基质的柔软性质使得颗粒能够以高体积分数填充。
