Analysis of Relationship between Peak Inspiratory Flow Rate and Amount of Drug Delivered to Lungs Following Inhalation of Fluticasone Propionate with a Diskhaler

Abstract

A fluticasone propionate dry powder inhaler with a Diskhaler (FP-DH), developed for inhalation of corticosteroids, is widely used for the treatment of asthma. A dry powder inhaler (DPI) is a breath controlled drug delivery system, in which a turbulent airstream is created by exploiting the patient's own inspiratory flow rate and is required to aerosolize particles for inhalation at a satisfactory peak inspiratory flow rate, which can achieve sufficient diffusion of the drug into the lungs. Therefore, it is considered that the inspiratory flow rate of the patient has a significant influence on the effects of drugs administered by an FP-DH.It was reported that 28 of 233 patients who inhaled corticosteroids for asthma could not achieve the optimal flow rate of 60 l/min, of whom 5 were treated for exacerbation of symptoms.1) Thus, it is very important to clarify the relationship between inspiratory flow rate and amount of drug delivered into the lungs when using a DPI. Although several in vitro studies have shown the delivery of drugs into the lungs at unvaried or slightly varied high flow rates, there is no known examination of the detailed relationship of these factors. [2][3][4][5][6] In the present study, we investigated the relationship between inspiratory flow rate and amount of drug delivered into the lungs by quantification of FP after inhalation with an FP-DH equipped with a twin impinger at various inspiratory flow rates. MATERIALS AND METHODS Materials A Flutide® 100 Rotadisk ® (GlaxoSmithKline K.K., Lot No. 355) was used as the FP-DH in the present study. A blister contains a mixture of 100 mg of microfine FP blended with lactose to a total weight of 25 mg. Geometric particle size of FP was Ϲ5 mm ( 90%м of particles), 7) aerodynamic particle size of FP was 3.3 mm, 8) and geometric particle size of lactose was 60-90 mm.7) To investigate the amount of drug inhaled, we used an inhalation simulator ( Fig. 1), which consisted of a flow recorder placed in a plastic air-tight box that covered the FP-DH equipped with a twin impinger and a vacuum pump. The FP-DH was kept at angle of 90°to the inlet of the impinger. The flow rate was recorded using a Vitalograph ® 2120 Handheld Storage spirometer (Vitalograph Ltd.), and data was transferred to a computer and analyzed using Vitalograph ® Spirotrac ® IV software. The relative amounts of the drug distributed inside a plastic box (a), and the device (b), throat (c), stage 1 (upper impinger) (d), and stage 2 (lower impinger) (e) were determined by measuring the amounts of drugs in those areas. The experiments were performed at 20°C with 30% relative humidity. The flow rates ranged from 18.7 to 77.3 l/min for 2 s. A Diskhaler is a dry powder type of inhaler that utilizes a breath controlled drug delivery system. The inspiratory flow rate of the patient would have a significant influence on the effects of drugs administered by a Diskhaler. Thus, we investigated the relationship between inspiratory flow rate and amount of drug delivered into the lungs when using a flutica...

Relationship between Amount of Drug Delivered to Lungs and Amount Released from Diskhaler by Inhalation with Tapping

“…a single inhalation without tapping) in the present study. 6) Further, there was a positive linear correlation between the amount released from the device and amount deposited in stage 2 with and without tapping (Fig. 4).…”

“…5) Therefore, peak inspiratory flow rates were set from 11.5 to 73.6 l/min in this study, since such peak inspiratory flow rates vary widely and some amounts of drug remained in the FP-DH following inhalation by patients with a low level of inspiratory ability less than 60 l/min in particular. 3,6,7) The technique used for tapping the device was three taps on the upper area of the rear side of the device by use of a fingernail, while being careful not to disperse the drugs outside of the device. During the experiments, the plastic box was opened after the first inhalation of drugs contained in a single blister and the second inhalation was carried out after tapping.…”

Investigation of Appropriate Inhalation Technique for Mometasone Furoate Dry Powder Inhaler

“…It is known that the PIFR of each patient has effects on drug delivery with a DPI 5,6,11,13) and each pharmaceutical company has prepared their own DPI training device for confirming inspiratory flow rate. However, no previous study examined the relationship between PIFR of the training device and drug deposition in the lungs.…”

“…Several studies set the inspiration time at 2 s by taking vital capacity into consideration, as the time required for a patient to strongly inhale with the DPI is approximately 2 s. 4,14) On the other hand, it has been noted that the dose emitted from a DPI is not affected by inspiration time. 8) Moreover, the average lung capacity of Japanese healthy adults is 3.5 L in males and 2.5 L in females.…”

Aerosol Delivery Devices for Obstructive Lung Diseases

“…Some in vitro studies indicate that the fine-particle dose from DPIs is reduced when inspiratory flow is Ͻ 60 L/min, [141][142][143][144] whereas other studies show little effect of flow. 145,146 Diskus lung delivery may be suboptimal with a peak inspiratory flow Ͻ 60 L/min.…”