Oral Liquid Medications
Fluid Thinking
Increasing patient compliance, while at the same
time ensuring correct dosing, is an ongoing task
for the OTC industry when it comes to liquid
medications, so selection of a suitable system
to dispense these formulations is paramount
Günter Nadler, Matthias Birkhoff and
Degenhard Marx at Aptar Pharma
Images: Aptar Pharma
On the other hand, liquids are
not easy to handle and dose,
which often means that the
medication is not taken as
prescribed by the physician or as
recommended by the manufacturer.
The challenging issue with all these products is
the preciseness of the dose required. Inconvenient packaging
and complicated dosing procedures are all contributing
factors. As of today, liquid medications are commonly packed
in conventional glass or open-mouth plastic bottles
equipped with dosing devices like measuring cups or spoons.
But patients are often not able to follow the instructions
provided by the manufacturer, and drug products are not
Figure 1 (above): Typical in-use appearance of standard bottle: the content
may cover the bottle and depending on the ingredients the screw may be
blocked by dried medication
always fully compatible with the dosing system with
which they are equipped. Confusing symbols and measuring
units result in over or under-dosages. Apart from the limited
– if not entirely absent – efficacy following under-dosing,
numerous reports of accidental overdoses are of more
serious concern. In a US study, 120 deaths in infants
from 1969 to 2006 were attributed to the overdose of
unprescribed antihistamines or decongestants (1).
Consequently, in 2009 the FDA issued a draft Guidance –
Pharmaceutical Manufacturing and Packing Sourcer August 2011 issue. © Samedan Ltd. 2011
Administration of medicines in liquid form is very common for
self-medication of medical conditions in adults as well as in
infants. Preferable over tablets, liquid medications are easy to
swallow, an important point for children and elderly people, and
provide a distinct benefit to these consumers as a result. Liquid
formulations should also provide a more rapid onset than solid
dosage forms with the same active ingredient. From a marketing
perspective, liquid formulations provide a wide range of options
to differentiate products: appealing to the senses of patients,
marketing people understood the need to create
products such as cough syrups with
different colours and flavours to
meet their sensitive taste and
other consumer’s preferences.
This should be enough to
guarantee a success story.
Dosage Delivery Devices for OTC Liquid Products – to address
existing safety concerns.
certainly influence the next purchase the consumer may
undertake when in the same or a similar condition.
However, there is still room for improvement. Just recently,
Shonna Yin et al of NYU School of Medicine published a study,
showing that top-selling paediatric OTC liquid medications
contained highly variable and inconsistent dosing directions
and measuring devices (2). Intelligent and well designed
packaging can help to provide a safe, as well as cutting-edge,
product to meet patients’ and consumers’ preferences. As
teaspoons and tablespoons are certainly an inappropriate
choice, this article tries to provide an overview on up-to-date
dosing systems for multi-dose bottles.
This problem is well known and has been discussed by the
industry for quite some time. Consequently, a range of more
or less sophisticated solutions is available. For dosing of
liquid medications, the simplest and still widely used method
is a measuring spoon or cup with appropriate markings.
Manufacturers only need to make sure that the appropriate
spoon is packed with the drug product it is designed for. The
advantages of using spoons or measuring cups are the very
low costs involved, and every consumer is familiar with the
method; at least people know in theory without consulting
the packaging information that a certain amount of liquid
needs to be poured onto the spoon or into the cup.
However, the interaction between liquid properties, the
bottle and the dispensing closure can sometimes turn this
into a challenging task. Not only will sticky medication with
sometimes alarming colours be found all over furniture and
clothing, serious dosing issues may occur when the spoon is
lost or confused with one for another medication bearing
different markings.
Simple Dosing: A Major Problem
For a long time, liquid medications have been dosed by the
number of drops dispensed. Alternatively, auxiliary devices
such as cups or spoons are used. Such dosing procedures in
general do not establish any risks for well-tolerated drugs
with a high safety margin. But many drugs do require exact
dosing in order to be effective and to prevent the side effects
caused by overdosing. For the drug manufacturer, easy
administration is obviously an important selling point.
Under-dosing will result in poor and slow symptom relief,
overdosing in more or less severe side effects. Such negative
experiences made with a particular drug product will
Figure 2: When using a measuring cup with a standard bottle it is hard
to hit the mark
Dosing syringes and sipping devices represent a step forward.
An individual locking system can prevent confusion between
different medications, while enabling precise dosing. These
solutions also prevent hands from becoming contaminated
Figure 3: SimpliSqueeze® is a unique silicone valve system enabling clean
dispensing out of flexible bottles and precise dosing into dosing caps or spoons
Figure 4: Examples of marketed products featuring metering dispensers
suitable for any liquid medications such as cough and cold
syrups, decongestants or other fluids.
Multi-Dose Pumps
during handling or products getting wasted. However, the
use of these systems is not intuitive – it can be complex and
additional information needs to be provided to the consumer.
After use, and certainly if there are long intervals of non-use
(such as cough and cold medication used seasonally), dosing
devices must be cleaned carefully to avoid clogging or
microbial growth inside.
New Technologies for Liquid Medications
A simple but efficient technology to enable precise
dosing into measuring spoons or cups is a silicone valve
closure system (see Figure 3). This technology was originally
developed for the food and beverage sector and has been
consequently adapted to the needs of pharmaceutical
applications. The unique silicone valve system involved
enables clean dispensing out of flexible containers. The
system does not provide any metering, so dosing caps or
spoons are still required, but it does facilitate convenient
and precise dosing significantly.
Another proven but more costly technology is the use
of metering pumps for exact dosing and convenient
handling (see Figure 4, page 95). Such pumps are available
at different sizes for a wide range of dosing volumes.
Packaging designers need to spend time selecting an
appropriate pump because dosing volume is just one
property that requires consideration. The pump must be
fully compatible with the targeted formulation. Another
important consideration is viscosity; not all pumps can
reliably dispense highly viscous products. If the medication
is of higher viscosity, the force required to deliver the dose
(actuation force) may increase to an unacceptable value, in
turn decreasing consumer compliance. Dosing problems
may occur because of trapped air bubbles, especially when
the bottle is shaken before use. If the pump is not used
for a long period of time, the outlet channels in the actuator
may be subject to clogging as a result of crystallisation
– in particular if a medication contains a lot of sugar. To
overcome such hurdles, some pumps incorporate sealing
features at the orifice. Alternatively, flexible caps which have
to be reattached after use are available. Another important
point to consider is that some pumps have metal parts
in the fluid path (such as springs or balls) which may be
incompatible with the drug. Oxidation (rusty metal parts)
and discolouration of the drug product are problems
reported in such cases. New pump generations with metal
free fluid paths and special design for high viscous products
can help addressing such issues. Metering pumps will
normally fit standard glass bottles with screw or snap on
closures, so the switch from a simple cap to a metering
pump is not complicated from a manufacturing point of
view. If such a change is considered, the package must
explain clearly about the new dosing technology to avoid
habitual use and consequent wrong dosing.
Conclusion
It keeps the neck of the bottle clean of medication and will
prevent clogging (see Figure 3). The valve prevents dripping
and spoiling of product even if the bottle is held in top
down position. To dispense the medication, the bottle must
be squeezed, the applied pressure controls the product flow.
The viscosity of the product may range from water to syrup.
As the system is plugged into the bottleneck, the protection
cap can be screwed on, using the outer thread of existing
containers with or without child-protection features.
Plenty of suitable bottles are available on the market using
polyethylene terephthalate (PET) as preferred material. The
advantages of such bottles are their low weight and high
resistance to fracture.
This type of dispensing system is today widely marketed for a
broad range of products in the food and beverage industry
such as honey, mustard or ketchup. Its features are also highly
According to recent market research, consumers reduced
their spending on OTC drugs and started to prefer private
label products (3). This development of consumer behaviour
within the triangle of prices, costs and perceived value will
certainly continue throughout 2011 and into 2012. However,
innovations in delivery mechanisms or ingredients will help
manufacturers to differentiate their products and defend
higher price positions. In order to maintain margins and
competitive advantages, companies must think about novel
products or features appreciated by consumers. If consumers
do not perceive value, they will maintain a level of loyalty to
a product which is mandatory to keep them from
considering private label alternatives.
Packaging suppliers can contribute substantially here to
balance convenient handling and patients expectations with
manufacturing costs. Last but not least, recent findings and
consequent expectations concerning dosing accuracy raised
by agencies such as the US FDA can be tackled more
appropriately with up-to-date technologies.
References
1. Dart RC et al, Pediatric fatalities associated with over
the counter (nonprescription) cough and cold medications,
Ann Emerg Med 53(4): pp411-417, 2009
2. Yin HS et al, Evaluation of consistency in dosing directions
and measuring devices for pediatric nonprescription liquid
medications, JAMA 304(23): E1-8, 2010
3. Chmelik S, Balancing Value and Safety: Drivers for
Consumer Purchasing Decisions, OTC Perspectives,
May 2010, pp23-25
About the Authors
Günter Nadler is Director, Business
Development, at Aptar Pharma Consumer
Health Care Division. He graduated in
Business Administration and in Mechanical
Engineering, and started his career at Aptar
11 years ago in R&D. Before joining the
Business Development Team in 2010 Günter
worked in different technical and commercial positions at
Aptar Pharma and gained a wide range of knowledge within
the pharmaceutical drug delivery industry. He was also Head
of the Product Management Team for several years.
Email: [email protected]
Matthias Birkhoff is Vice President, Marketing,
in Aptar Pharma. He joined the former Ing
Erich Pfeiffer GmbH in 1998 and was Sales
Director for the Asia Pacific region before
getting involved in business development and
marketing. After obtaining a nursing degree
he studied medicine at the University of
Düsseldorf in Germany. Email: [email protected]
Degenhard Marx is Director Scientific
Affairs within the Consumer Healthcare
division. Following the study of veterinary
medicine and the successful completion
of his PhD at the University of Leipzig,
Degenhard joined the Arzneimittelwerke
Dresden/Asta Medica co-operate research
in 1992. In 2001 he took over a senior research position at
Altana Pharma/Nycomed in Constance, Germany. During
this time in the pharmaceutical industry he collected ample
experiences in the drug development of anti-inflammatory
and cardio-vascular drugs. In 2008 he became Business
Development Manager at Aptar Pharma.
Email: [email protected]