Issue link: http://www.e-digitaleditions.com/i/830814
Inhalation JUNE2017 13 pharmaceutically active drugs are developed, dose con- trol will become more important. This is already being seen in increased restrictions by regulators, such that modern drug approval is related to the specific nebulizer used in the later phases of a clinical trial program, with an advisory in the instructions for use of the launched product stating that the performance of other devices has not been evaluated. For general-purpose nebulizers intended for use with existing drug formulations, a manufacturer must docu- ment the performance of the new nebulizer device according to the results of tests defined in test standards. 32- 34 The tests and parameters defined in the standards offer simplified test model approximations of the fate of aerosol droplets/particles, to balance practicality of the tests with relevance to the clinical situation. Recent work has shown an area of improvement that seems practical and may be of increasing importance in the delivery of modern pharmaceuticals for which dose is likely to be more of a factor. Hatley et al. showed the impact of vary- ing the inhalation:exhalation (I:E) ratio of the simple model of the breathing cycle used in the test standards upon the delivered dose and respirable delivered dose from nine different brands of nebulizer with five different modes of operation (conventional jet; venturi jet; breath- enhanced jet; mesh; and breath-activated jet/mesh). 34 The results showed the usual wide variation (up to 2.5 times difference) in delivered dose and an even greater, four-fold difference in respirable delivered dose between the different nebulizers, when using the test breathing pattern mandated in the standards. But there was also a reduction of up to 60% in respirable delivered dose from non-breath-activated nebulizers when tested with breath- ing patterns defined in the standards, compared to a breathing pattern typical of a patient with severe airflow obstruction/restriction. In contrast, the breath-activated jet nebulizer demonstrated only a 10% change in the res- pirable delivered dose over the same range, while the res- pirable delivered dose from the breath-activated mesh nebulizer was independent of I:E ratio, although the treatment time from both breath-activated nebulizers was significantly increased, providing further evidence why mesh nebulizers, particularly breath-activated mod- els, are more suited to drug development. Neglected opportunities for nebulized therapies For the 50% of COPD patients who are discharged from the hospital with a nebulized drug, they may find themselves switched from a once-daily, anti-muscarinic inhaler to a four-times-per-day nebulized combination of short-acting β-agonist and anti-muscarinic, with a consequent significant increase in treatment time. It is well documented that burden of disease can adversely affect adherence 35 and it has been estimated that a reduction in adherence of 20% leads to an increase in adverse events of more than 10% in COPD patients. 36 It is therefore not surprising that patients are less likely to be readmitted when prescribed a long-acting, nebu- lized β-agonist, compared to a short-acting product. 37 Driving Successful Drug Delivery by Bridging the Gaps between Patient Usage, Device Performance, and Formulation Learn more at: goproveris.com/labstudies F O R M U L A T I O N P A T I E N T U S A G E D E V I CE P E R F O R M A NCE