The Rate of Drug Particle Detachment from Carrier Crystals in an Air Classifier-Based Inhaler

Boer, Anne H. de; Hagedoorn, Paul; Gjaltema, Doetie; Lambregts, Dorette; Irngartinger, Meike; Frijlink, Henderik W.

doi:10.1007/s11095-004-7668-4

Cited by 22 publications

(30 citation statements)

References 34 publications

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“…There have been several reports on the relationship between peak inspiratory flow rate and drug deposited by various systems, 3,4) with a Diskhaler shown to deliver approximately 12% of the initial dose. 11,12) The present results support and confirm those previous studies, as the estimated amount of drug deposited in stage 2 was 10.1 mg at a flow rate of 60 l/min, adequate for obtaining a good effect from a Diskhaler and similar to the 12% reported previously.…”

Section: Discussionmentioning

confidence: 99%

“…The curves generated from the estimated values were well matched to the values obtained in the experiment. (3) The doses deposited in stage 2 were estimated to be 2.9 mg at a flow rate of 20 l/min, 6.6 mg at 30 l/min, 8.4 mg at 40 l/min, 10.1 mg at 60 l/min, and 11.3 mg at 90 l/min.…”

Section: Analysis Of Relationship Between Amount Of Drug Released Fromentioning

confidence: 99%

“…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. …”

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

Yokoyama

Yamamura

Ozeki

et al. 2007

Biological & Pharmaceutical Bulletin

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Relationship Between Amount Of Drug Released Fromentioning

confidence: 99%

mentioning

confidence: 99%

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

Yokoyama

Yamamura

Ozeki

et al. 2007

Biological & Pharmaceutical Bulletin

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“…1). (1) Next, the relationship between the amount of drug released from the device and amount deposited in stage 2 was analyzed. The amount of drug deposited in stage 2 was calculated from the peak inspiratory flow rate, by integration of Eq.…”

Section: Relationship Between Amount Of Drug Released From Fp-dh and mentioning

confidence: 99%

“…Further, it has been proposed that the inspiratory ability of the patient has an influence on the amount remaining in the device. 1,2) Since dosing performance of an FP-DH is likely dependent on patient inspiration capability, the method of inhalation is important clinically for delivery of the proper dosage. In our previous study, patients found some amounts of drugs remaining in the device after a single inhalation with an FP-DH, while those remaining after a second inhalation were decreased by tapping the device after the first inhalation.…”

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confidence: 99%

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

Yokoyama

Yamamura

Abe

et al. 2007

Biological & Pharmaceutical Bulletin

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It is well known that drug residue remains in a fluticasone propionate Diskhaler (FP-DH) following a single inhalation. Thus, the inspiratory ability of the patient has an influence on the effects of the drug. In a previous study, we reported that the amount of drug remaining in an FP-DH was decreased by tapping the device after the first inhalation. In the present study, we investigated the relationship between the amount of drug delivered to the lungs and amount of drug released from the FP-DH by inhalation along with tapping using an in vitro model. We measured the amounts delivered to the throat, stage 1, and stage 2 of a twin impinger device by HPLC-UV, following inhalation and tapping of 100 m mg of FP-DH at various inspiratory flow rates, which ranged from 11.5 to 73.6 l/min for 2 s. A positive linear correlation between the amount of drug released from the FP-DH and that deposited in stage 2 was observed. Amounts deposited in stage 2 following tapping were estimated to be 6.0 m mg at an inspiratory flow rate of 20 l/min and 10.6 m mg at 60 l/min, while those without tapping were 2.0 m mg and 10.2 m mg, respectively. Notably, at an inspiratory flow rate of 20 l/min, the amount of drug deposited in stage 2 by tapping was increased about 3-fold in comparison to that without tapping. Our results indicate that the amount of drug deposited in stage 2, i.e., the lung in our model, is increased by tapping of the device, which would be particularly helpful for patients with a lower level of inspiratory ability.

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In Vitro Performance Testing for Pulmonary Drug Delivery

Son¹,

Mitchell²,

McConville³

2011

Controlled Pulmonary Drug Delivery

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The Rate of Drug Particle Detachment from Carrier Crystals in an Air Classifier-Based Inhaler

Cited by 22 publications

References 34 publications

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

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

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

In Vitro Performance Testing for Pulmonary Drug Delivery

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