The present study was aimed at the development of a re-dispersible multi-dose suspension based on coated microparticles to ensure easy swallowing and sustained release of metoprolol succinate. To provide sustained release of metoprolol succinate, the microparticles were prepared by drug loading and Eudragit® NM coating in a fluid-bed coater. Compositions of the liquid suspension vehicle were selected to reduce solubility of metoprolol succinate. The effect of vehicle composition and suspension storage time at RT on drug leaching into the suspension vehicle and on the drug release profile were investigated. The approach allowed a re-dispersible multi-dose suspension of metoprolol microparticles which, after one month’s storage, displayed negligible drug leaching into the suspension vehicle and a sustained release profile comparable to the profile before storage.

1. British Journal of Pharmacy
www.bjpharm.hud.ac.uk
Development of multi-dose oral sustained release suspensions for older
patients with dysphagia
Kavil Patela
, Valentyn Mohylyuka
, Darragh Murnanea,b
, Craig Richardsonb
Fang Liua,b
*
a Department of Pharmacy Pharmacology and Postgraduate Medicine, University of Hertfordshire,
Hatfield, UK; b Fluid Pharma Ltd., Leeds Innovation Centre, 103 Clarendon Road, Leeds, LS2 9DF, UK
A R T I C L E I N F O
*Corresponding author.
Tel.: +44 1707 284 273
Fax: +44 1707 284 506
E-mail: f.liu3@herts.ac.uk
KEYWORDS: Microparticles;
sustained release; suspension;
swallowing
S U M M A R Y
The present study was aimed at the development of a re-dispersible multi-dose
suspension based on coated microparticles to ensure easy swallowing and sustained
release of metoprolol succinate. To provide sustained release of metoprolol
succinate, the microparticles were prepared by drug loading and Eudragit® NM
coating in a fluid-bed coater. Compositions of the liquid suspension vehicle were
selected to reduce solubility of metoprolol succinate. The effect of vehicle
composition and suspension storage time at RT on drug leaching into the suspension
vehicle and on the drug release profile were investigated. The approach allowed a
re-dispersible multi-dose suspension of metoprolol microparticles which, after one
month’s storage, displayed negligible drug leaching into the suspension vehicle and
a sustained release profile comparable to the profile before storage.
BY 4.0 Open Access 2018 – University of Huddersfield Press
INTRODUCTION
Most oral dosage forms such as tablets and capsules
are not suitable for older people with swallowing
difficulties. Capsule opening and tablet crushing are
commonly used to overcome this problem. In
addition to safety and legal concerns, this approach
cannot be applied to sustained products because of
the loss of their functionality, consequently causing
dose dumping and, undesirable side effects and even
toxicity. The number of appropriate medicines for
older patients with swallowing difficulties is therefore
limited because of the absence of suitable oral dosage
forms. One of the most appropriate forms of
medicines for patients with swallowing difficulties
are liquid formulations (Liu et al., 2016). The objective
of this study was to develop a stable, re-dispersible
multi-dose liquid suspension based on sustained
release microparticles to facilitate swallowing in older
patients with dysphagia.
MATERIALS AND METHODS
Metoprolol succinate (Sinobio Chem. Co. Ltd., China)
drug loaded and sustained release film-coated
microparticles were prepared in a fluid-bed coater
(Mini-Glatt, Glatt AG, Germany) using MCC-cores
(Cellets® 90, IPC Process-Centre GmbH, Germany)
with 86.5 µm D50 particle size (laser diffraction
method, Sympatec), HPMC (Methocel E5, Colorcon,
UK), aqueous Eudragit® NM 30 D (Evonik AG,
Germany) based coating with admixture of talc
(Pharma M, Imerys Talc, Italy) and magnesium
stearate (Acros Organics, Belgium or Sudeep Pharma
Pvt. Ltd., India).
Oral liquid suspension vehicles were prepared by
dissolving/mixing excipients in/with deionised
water. Metoprolol succinate (MS) solubility in water
and suspension vehicles was measured using a shake-
flask method (3 days at RT). Suspensions were
prepared by adding the sustained release
microparticles to different ready-to-use vehicles to
obtain the appropriate dose. Drug leakage from the
coated microparticles in the suspension vehicle
(Bottle-test (Dashevskiy et al., 2017)) was carried out
during shelf storage (1 month at RT). Dissolution tests
of the microparticles before and after storage were
performed using USP II method (50 rpm) in 500 ml of
Proceedings of the APS@FIP Conference 2018

2. PBS pH 6.8 (Copley Scientific, UK). UV-absorption
was measured (T80, PG Instruments Ltd., UK) at
274 nm.
RESULTS AND DISCUSSION
Sustained-release MS microparticles were produced
by film coating using a fluid bed coater. The average
particle size of the coated particles was < 200 µm. The
achieved yield of coated particles was more than 99%.
The solubility of metoprolol succinate (MS) in the
suspension vehicles significantly reduced with
increasing concentration of Vehicle 1 and/or Vehicle
2 (Fig. 1) in comparison to its water solubility.
Fig. 1. Effect of vehicle composition on the solubility of MS.
After one month’s storage of MS microparticles in the
selected suspension vehicles, the MS leakage from
microparticles into the liquid vehicle did not exceed
1.7 % of dose (Tab. 1).
Table 1. MS leakage in chosen vehicles after one month’s
storage
Characteristics
Vehicle 1/ Vehicle 2 / Water a
50/30/20 20/50/30 30/45/25
MS leakage after 1 month
of storage, % of dose
1.7 1.3 1.6
a weight proportion of ingredients (%/%/%)
The dissolution profiles after one month of
suspension storage in different vehicles were similar
to the initial profile (similarity factor > 62% for all
profiles, Fig. 2).
Fig. 2. Effect of vehicle composition after one month’s
storage on the dissolution of MS from microparticle
suspension (n=6, SD<3%).
CONCLUSIONS
Re-dispersible multi-dose suspensions based on
coated metoprolol succinate sustained-release
microparticles were developed. After one month’s
storage at room temperature, there was negligible
leakage of drug into any of the vehicle compositions
tested and, regardless of vehicle choice, the sustained
release profile of metoprolol did not significantly
change upon storage.
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