ABSTRACT

Introduction

Respiratory infections are a major cause of morbidity and mortality. As an alternative to systemic drug administration, inhaled drug delivery can produce high drug concentrations in the lung tissue to overcome resistant bacteria. The development of inhaled fixed-dose combination powders (I-FDCs) is promising next step in this field, as it would enable simultaneous drug-drug or drug-adjuvant delivery at the site of infection, thereby promoting synergistic activity and improving patient compliance.

Areas covered

This review covers the clinical and pharmaceutical rationales for the development of I-FDCs for the treatment of respiratory infections, relevant technologies for particle and powder generation, and obstacles which must be addressed to achieve regulatory approval.

Expert opinion

I-FDCs have been widely successful in the treatment of asthma and chronic obstructive pulmonary disease; however, application of I-FDCs towards the treatment of respiratory infections carries additional challenges related to the high dose requirements and physicochemical characteristics of anti-infective drugs. At present, co-spray drying is an especially promising approach for the development of composite fixed-dose anti-infective particles for inhalation. Though the majority of fixed-dose research has thus far focused on the combination of multiple antibiotics, future work may shift to the additional inclusion of immunomodulatory agents or repurposed non-antibiotics.

中文翻译：

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用于治疗呼吸道感染的吸入固定剂量复方粉剂

摘要

介绍

呼吸道感染是发病率和死亡率的主要原因。作为全身给药的替代方案，吸入给药可以在肺组织中产生高药物浓度以克服耐药细菌。吸入固定剂量复方粉剂 (I-FDC) 的开发有望在该领域迈出下一步，因为它将能够在感染部位同时递送药物-药物或药物-佐剂，从而促进协同作用并提高患者依从性。

覆盖区域

本综述涵盖了开发用于治疗呼吸道感染的 I-FDC 的临床和药物原理、颗粒和粉末生成的相关技术以及获得监管批准必须解决的障碍。

专家意见

I-FDC 在治疗哮喘和慢性阻塞性肺疾病方面取得了广泛的成功；然而，将 I-FDC 应用于治疗呼吸道感染带来了与抗感染药物的高剂量要求和理化特性相关的额外挑战。目前，共喷雾干燥是开发用于吸入的复合固定剂量抗感染颗粒的特别有前途的方法。尽管迄今为止大多数固定剂量研究都集中在多种抗生素的组合上，但未来的工作可能会转向额外加入免疫调节剂或重新利用非抗生素。