Determination of the minimum dose of lactose drug carrier
that can be sensed during inhalation

M. A. HIGHAM, A. M. SHARARA, R. P. MAGEE & P. W. IND
Respiratory Division, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du
Cane Road, London WI2 ONN

Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy volunteers
without respiratory symptoms inhaled seven different doses of lactose and a placebo
(empty) dose through the four place Diskhaler® device, in order to determine the lowest
dose that could be reliably sensed. The minimum dose for which all subjects
reported taste or feel sensations was 10 mg. This has implications regarding the
amount of carrier used in future drug delivery systems.

Keywords lactose inhalation sensation

Introduction

The inhaled route has well established benefits for
drug delivery in the treatment of airway diseases, and
a number of different inhaled drug delivery systems
have been developed [1]. Dry powder inhalers have
certain advantages over metered dose inhalers since
they do not involve aerosol constituents, which can
have direct adverse effects on health [2] and indirect
effects due to their impact on the environment [3].
Being breath operated they obviate the need for handbreath
coordination and are considered easier to use
[4]. Dry powder devices commonly use sealed individual
doses of medication ('caps' or 'blisters'),
allowing patients and physicians to monitor usage
and thus potentially improving compliance. Each
dose usually comprises active drug and lactose
carrier, the dose of lactose varying considerably in
different devices.
It has been proposed that one advantage of using
lactose as a carrier is that it may allow patients to
register that they have taken a dose, due to its irritant
effect on the back of the throat [5]. We have observed
that patients often complain that they cannot detect
actuation of one of the dry powder devices which
delivers pure drug without any lactose carrier. However,
we have found no published reports of controlled
studies of individuals' ability to recognise that
a dose of medication has been inhaled. The present
study was undertaken in order to determine the minimum
dose of lactose which can be reliably sensed
when inhaled. This may have implications for future
development of inhaled drug formulations.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.1995....