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患者为中心的长效注射和植入式平台—工业视角。

Patient-Centric Long-Acting Injectable and Implantable Platforms─An Industrial Perspective.

机构信息

Independent Researcher, Havertown, Pennsylvania 19083, United States.

Gilead Sciences, 333 Lakeside Drive, Foster City, California 94403, United States.

出版信息

Mol Pharm. 2024 Sep 2;21(9):4238-4258. doi: 10.1021/acs.molpharmaceut.4c00665. Epub 2024 Aug 19.

Abstract

The increasing focus on patient centricity in the pharmaceutical industry over the past decade and the changing healthcare landscape, driven by factors such as increased access to information, social media, and evolving patient demands, has necessitated a shift toward greater connectivity and understanding of patients' unique treatment needs. One pharmaceutical technology that has supported these efforts is long acting injectables (LAIs), which lower the administration frequency for the patient's provided convenience, better compliance, and hence better therapeutical treatment for the patients. Furthermore, patients with conditions like the human immunodeficiency virus and schizophrenia have positively expressed the desire for less frequent dosing, such as that obtained through LAI formulations. In this work, a comprehensive analysis of marketed LAIs across therapeutic classes and technologies is conducted. The analysis demonstrated an increasing number of new LAIs being brought to the market, recently most as aqueous suspensions and one as a solution, but many other technology platforms were applied as well, in particular, polymeric microspheres and in situ forming gels. The analysis across the technologies provided an insight into to the physicochemical properties the compounds had per technology class as well as knowledge of the excipients typically used within the individual formulation technology. The principle behind the formulation technologies was discussed with respect to the release mechanism, manufacturing approaches, and the possibility of defining predictive in vitro release methods to obtain in vitro in vivo correlations with an industrial angle. The gaps in the field are still numerous, including better systematic formulation and manufacturing investigations to get a better understanding of potential innovations, but also development of new polymers could facilitate the development of additional compounds. The biggest and most important gaps, however, seem to be the development of predictive in vitro dissolution methods utilizing pharmacopoeia described equipment to enable their use for product development and later in the product cycle for quality-based purposes.

摘要

在过去十年中,制药行业越来越关注以患者为中心,加上信息获取、社交媒体的发展以及患者需求的变化等因素,推动了医疗保健领域的变革,这使得人们需要更加注重患者的独特治疗需求,并加强医患之间的沟通。一种支持这些努力的制药技术是长效注射剂(LAIs),它降低了患者的给药频率,为患者提供了便利,提高了患者的顺应性,从而为患者提供了更好的治疗效果。此外,患有艾滋病和精神分裂症等疾病的患者也积极表示希望减少给药频率,例如通过 LAI 制剂获得的频率。在这项工作中,对治疗类别和技术的市售 LAIs 进行了全面分析。分析表明,越来越多的新型 LAI 被推向市场,最近大多数是水性混悬剂,一种是溶液,但也应用了许多其他技术平台,特别是聚合物微球和原位形成凝胶。对技术的分析深入了解了化合物按技术类别具有的物理化学性质,以及在各个制剂技术中常用的赋形剂知识。从工业角度出发,讨论了制剂技术背后的原理,包括释放机制、制造方法以及定义预测性体外释放方法的可能性,以获得体外体内相关性。该领域仍然存在许多空白,包括更好的系统性制剂和制造研究,以更好地了解潜在的创新,还需要开发新的聚合物,以促进其他化合物的开发。然而,最大和最重要的差距似乎是开发利用药典描述设备的预测性体外溶出度方法,以将其用于产品开发,并在产品周期的后期用于基于质量的目的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae56/11372838/b46a768b4a92/mp4c00665_0001.jpg

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