University of Groningen

Dry powder inhalationKoning, Johannes Petrus de

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.

Document VersionPublisher's PDF, also known as Version of record

Publication date:2001

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):Koning, J. P. D. (2001). Dry powder inhalation: technical and physiological aspects, prescribing and uses.n.

CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.

Download date: 10-02-2018

'U\�3RZGHU�,QKDODWLRQ

7HFKQLFDO�DQG�3K\VLRORJLFDO�$VSHFWV��3UHVFULELQJ�DQG�8VH

5,-.681,9(56,7(,7�*521,1*(1

'U\�3RZGHU�,QKDODWLRQ

7HFKQLFDO�DQG�3K\VLRORJLFDO�$VSHFWV��3UHVFULELQJ�DQG�8VH

3URHIVFKULIW

WHU�YHUNULMJLQJ�YDQ�KHW�GRFWRUDDW�LQ�GH:LVNXQGH�HQ�1DWXXUZHWHQVFKDSSHQDDQ�GH�5LMNVXQLYHUVLWHLW�*URQLQJHQ

RS�JH]DJ�YDQ�GH5HFWRU�0DJQLILFXV��GU��'�)�-��%RVVFKHU�

LQ�KHW�RSHQEDDU�WH�YHUGHGLJHQ�RSPDDQGDJ���PHL�����

RP�������XXU

GRRU

-RKDQQHV�3HWUXV�GH�.RQLQJ

JHERUHQ�RS���VHSWHPEHU�����WH�$OSKHQ�DDQ�GHQ�5LMQ

3URPRWRUHV

3URI�'U��7K�)�-��7URPS3URI�'U��+�:��)ULMOLQN

5HIHUHQWHQ

'U��7K�:��YDQ�GHU�0DUN'U��3�0�-��&RHQHJUDFKW

%HRRUGHOLQJVFRPPLVVLH

3URI�'U��*�+��.RsWHU3URI�'U��/�7�:��GH�-RQJ���YDQ�GHQ�%HUJ3URI�'U��-�3��5HPRQ

3ULQWHG�YHUVLRQ� ,6%1���������������(OHFWURQLF�YHUVLRQ� ,6%1��������������[

voor Jokevoor mijn ouders

3DUDQLPIHQ

0DULQHOOD�9LVVHU*HUD�2HOHQ

��-�3��GH�.RQLQJ��*URQLQJHQ������

Printed version ISBN 90-367-1393-5

Electronic version ISBN 90-367-1401-x

NUGI 746

The research project described in this thesis was performed within the framework of the

research school GUIDE, and was supported by Groningen Centre for Drug Research (GCDR),

AstraZeneca B.V, Sofotec (formally ASTA Medica), and ‘Stichting Doelmatige

Farmaceutische Zorg Drenthe / Hanzeland’ (DFZ).

Printing of this thesis was financially supported by:

Groningen University Institute for Drug Exploration (GUIDE)

Rijksuniversiteit Groningen

AstraZeneca B.V.

Boehringer Ingelheim B.V.

GlaxoSmithKline

3M Pharma Nederland B.V.

Schering-Plough

Printing: Stichting Drukkerij C. Regenboog, Groningen, the Netherlands

vii

&217(176

&RQWHQWV

Preface ix

Introduction xi

Chapter 1 Introduction to Inhalation Therapy with Dry Powder Inhalers �

3DUW���� 7HFKQLFDO�DQG�3K\VLRORJLFDO�$VSHFWV

Chapter 2 Effect of Resistance to Airflow on the Inspiratory Flow Curve ��

Chapter 3 Relationship between Inspiratory Flow Through Simulated Dry ��

Powder Inhalers and Peak Maximal Inspiratory Pressure

Chapter 4 Inhalation Through Dry Powder Inhalers in Chronic Obstructive ��

Lung Disease Patients with Reduced Peak Maximal Inspiratory Pressure

Chapter 5 Daily use of a Dry Powder Inhaler Increases Peak Maximal ��

Inspiratory Pressure

Chapter 6 Effect of Peak Inspiratory Flow and Flow Increase Rate on In Vitro ��

Drug Deposition from Four Dry Powder Inhaler Devices

Chapter 7 Errors in Pneumotachograph Readings Caused by an Add-on Device ��

3DUW���� $VSHFWV�RI�3UHVFULELQJ�DQG�8VH

Chapter 8 Choice of an Inhaler Device in the Treatment of Asthma and COPD ���

by Chest Physicians, General Practitioners, and Pharmacists

Chapter 9 The Use of Dry Powder Inhalers – Inhalation-Instructions ���

Chapter 10 Patient Compliance in the Treatment of Pulmonary Disease Based���

on Prescription Data from Pharmacies

&RQFOXVLRQV

Chapter 11 Final Remarks and Perspectives ���

List of Abbreviations ���

Summary ���

Samenvatting ���

Dankwoord ���

Curriculum Vitae ���

viii

&217(176

hans

ix

35()$&(

3UHIDFH

*URQLQJHQ�&HQWUH�IRU�'UXJ�5HVHDUFK

,QQRYDWLRQ�E\�&ROODERUDWLRQ

The Groningen Centre for Drug Research (GCDR), founded in 1986, is committed to the

stimulation of pharmaceutical research at the University Centre for Pharmacy in Groningen,

in collaboration with industrial partners. The pharmacy research groups collaborate with a

large number of companies and health care organisations in many different projects. The

activities range from small problem-solving projects to major research programmes running

for several years. The expertise available is not only applicable for pharmaceutical companies

and health care organisations, but is also very useful for other kinds of industrial research

activities, especially those in the fields of food and agricultural science.

The general aim of the GCDR is to carry out both fundamental and applied research into the

methodologies, which are necessary for the innovative design, development and evaluation of

new drugs and their dosage forms. These research areas cover the entire field of drug

research, from drug design to the post-marketing surveillance of any given specific

compound.

In 1995 the GCDR initiated a competition for research proposals of a multidisciplinary nature

for the research groups involved in the GCDR to support the GCDR mission statement

innovation by collaboration. Finally, the multidisciplinary research proposal initiated by

Prof. Dr. Ir. C.F. Lerk (former head of department of Pharmaceutical Technology and

Biopharmacy), Prof. Dr. Th.F.J. Tromp (Pharmacy Practice), Dr. P.M.J. Coenegracht

(Chemometrics), and Dr. Th.W. van der Mark (department of Pulmonology, University

Hospital Groningen), was rewarded by the scientific board of the department of Pharmacy of

the University of Groningen, and the GCDR with a research grant. The results obtained within

this multidisciplinary research setting are presented in this thesis.

Groningen Centre for Drug Research

x

*521,1*(1&(175()25'58*5(6($5&+

Groningen centre for drugs research Hans de Koning

xi

,1752'8&7,21

,QWURGXFWLRQ

*XLGH�WR�WKH�5HDGHU

This thesis is the result of a project that was initiated by the Groningen Centre for Drug

Research (GCDR). The activities were carried out in four different research groups as a

combined project. The research groups were Pharmaceutical Technology and Biopharmacy

(Prof. Dr. H.W. Frijlink), Pharmacy Practice (Prof. Dr Th.F.J Tromp), Chemometrics

(Dr. P.M.J. Coenegracht), all three of the Groningen Research Institute of Pharmacy (GRIP),

and the research group of Pulmonology (Dr. Th.W. van der Mark) from the University

Hospital of Groningen. The setting of this research with input from the different research

groups enabled a broad approach in investigating inhalation therapy with dry powder inhalers.

This thesis is divided in a general introduction, two major experimental parts and finally some

remarks and perspectives.

In chapter 1, a general introduction to inhalation therapy with dry powder inhalers is

presented. The aim of this chapter is to provide a brief introduction and background to all

aspects investigated as presented in this thesis.

Part one of this thesis deals with the technical and physiological aspects of dry powder

inhalations. The aim of this section is to investigate the effects of inhalation performances on

the output of fine particles from dry powder inhalers.

Chapter 2 describes the effect of inhalation through a resistance to airflow on the inspiratory

flow curve. The aim of this study is to define the essential parameters for a proper description

of the inspiratory flow curve through a resistance to airflow, such as dry powder inhaler.

In chapter 3 and chapter 4, the relationship between the inspiratory muscle strength and the

inspiratory flow curve is investigated in healthy subjects, asthmatics, mild to moderate COPD

patients and COLD patients with significantly reduced peak maximal inspiratory pressure.

The aim of the study was to determine the relationship between a human performance

parameter and the parameters of the inspiratory flow curve.

xii

*8,'(727+(5($'(5

Chapter 5 deals with the training effects of the use of high resistance to airflow dry powder

inhalers. The aim of this study was to investigate the effect of daily use of a high resistance to

airflow dry powder inhaler, as an inspiratory muscle training, on the peak maximal inspiratory

pressure and peak inspiratory flow.

In chapter 6, the results are presented from testing of the performance of four corticosteroid

dry powder inhalers. The test conditions were based on previously measured inspiratory flow

parameters. In this study the effects of both the peak inspiratory flow and the flow increase

rate on the fine particle output from the dry powder inhalers were investigated.

In chapter 7, a theoretical explanation and experimental solution of errors in

pneumotachograph readings, as found during measurements with an add-on device, as

described in chapter 3 and chapter 4, is presented.

Part two of this thesis deals with aspects of prescribing and use of dry powder inhalers. The

aim of this section is to provide knowledge about the patients’ use of dry powder inhalers and

information about the intervention possibilities for changes in prescribing of inhaled

medication.

Chapter 8 deals with the evoked set for inhalation devices as applied by chest physicians,

general practitioners and pharmacists. The aim of this study was to investigate which choice

criteria and actual (technical) knowledge about inhaler devices is involved at the prescribing

of an inhaler device in the treatment of asthma and COPD.

Chapter 9 provides an overview of inhalation-instructions to patients for commonly used dry

powder inhalers. The aim of this study is to connect technical knowledge about dry powder

inhalers with an inhalation-instruction. This combined information can be used when

inhalation-instruction to patients is given.

In chapter 10 the patient compliance of inhaled corticosteroids is investigated, based on

prescription data from pharmacies. The aim of this study is to measure differences in patient

compliance in relation to the used inhaler device and age of the patient.

Final remarks and perspectives are given in Chapter 11. Aim of this chapter is to merge the

research results on dry powder inhalation as investigated from the different perspectives. The

different perspectives are the result of the multidisciplinary input of the different research

groups.