دانلود رایگان مقاله انگلیسی تکنولوژی ارسال در استنشاق دوز اندازه گیری شده فشرده برای داروهای چند دوزی در درمان بیماری های تنفسی - الزویر 2018

abstract

Technologies for long-term delivery of aerosol medications in asthma and chronic obstructive pulmonary disease have improved over the past 2 decades with advancements in our understanding of the physical chemistry of aerosol formulations, device engineering, aerosol physics, and pulmonary biology. However, substantial challenges remain when a patient is required to use multiple inhaler types, multiple medications, and/or combinations of medications. Combining multiple drugs into a single inhaler while retaining appropriate dosing of the individual agents in the combination may enhance patient adherence to therapy and reduce device errors that occur when patients are using multiple inhalers. Pressurized metered-dose inhaler (pMDI) devices are widely used by patients for acute symptom relief as well as maintenance treatment, so the pMDI may be a suitable option with which to explore medication combinations. However, optimizing drug formulation remains a key challenge for pMDI delivery systems. This article introduces a new pMDI formulation approach: co-suspension delivery technology, which uses drug crystals with porous, low-density phospholipid particles engineered to deliver combinations of drugs to the airways with accurate and consistent dosing via pMDIs, independent of medication types and combinations. We describe the key characteristics of pMDIs, and discuss the rationale for the co-suspension delivery technology platform based on the limitations associated with traditional formulations. Finally, we discuss the clinical implications of co-suspension delivery technology for developing combination drug therapies administered by pMDIs.

8. Summary

Although pMDIs are currently the most widely used aerosol delivery devices, challenges associated with pMDIs have meant that major drug classes and their combinations are not available for this inhaler type. As a result, there is a need for alternative formulation and delivery approaches. In its fundamental form, cosuspension delivery technology is a simple and versatile formulation platform for pMDIs. The platform uses drug crystals, which are the naturally stable form of a drug, and phospholipid porous particles, which are naturally buoyant low-density particles, together. This approach allows the potential to formulate drugs with a wide range of pharmacological properties, physicochemical attributes, and doses, whether alone or in combinations. Thus, co-suspension delivery technology provides an opportunity to combine multiple drugs with highly variable characteristics in the same pMDI device while maintaining uniformity and suspension stability, thereby overcoming the variability associated with conventional formulations. Consistent delivery of small and large molecules can now be contemplated from one inhaler. This formulation approach has shown the ability to target all regions of lungs consistently. In addition, the co-suspension delivery technology formulation has been shown to have consistent drug delivery across various pMDI patient-use scenarios. By solving some of the longest-standing challenges with pMDI-based drug delivery, the co-suspension delivery technology has the potential to enable development of multiple therapies in one inhaler type and increase patient adherence to therapy.