Review

Digestion 2003;67:1–5
DOI: 10.1159/000070393

Lansoprazole Fast Disintegrating Tablet:

A New Formulation for an Established
Proton Pump Inhibitor
Fabio Baldi a Peter Malfertheiner b
a Department of Gastroenterology, Metabolic and Infectious Diseases, S. Orsola-Malpighi Hospital, Bologna, Italy,
and b Department of Gastroenterology, Hepatology and Infectious Diseases, Otto van Guericke University,
Magdeburg, Germany

Key Words efit to those with active life-styles who do not always
Acid-related disorders W Lansoprazole W Orally have water available, patients who have difficulty in
disintegrating tablet W Patient-friendly formulation W swallowing, and elderly patients.
Proton pump inhibitor Copyright © 2003 S. Karger AG, Basel

Abstract Introduction
Lansoprazole is a proton pump inhibitor (PPI) which is an
effective and well-tolerated treatment option in the man- Lansoprazole is a proton pump inhibitor (PPI) which
agement of acid-related disorders. Lansoprazole fast dis- inactivates the final step in the gastric acid secretion path-
integrating tablet (LFDT) – a new, patient-friendly and way in gastric parietal cells in a dose-dependent manner.
more convenient formulation of lansoprazole which can Bioavailability is 85% after the first dose – the highest
be taken with or without water – is the first PPI to be among PPIs [1–5] – and acid inhibition is swift, resulting
made available as an orally disintegrating tablet. It repre- in rapid relief of symptoms [6]. Lansoprazole also exhibits
sents an innovative drug delivery system, comprising antibacterial activity against Helicobacter pylori in vitro
enteric-coated microgranules of lansoprazole com- [7–9].
pressed with an inactive, rapidly dispersing matrix to Seventeen years of clinical experience worldwide have
form a tablet. When the tablet is placed on the tongue shown lansoprazole to be an effective and well-tolerated
and sucked gently it disintegrates rapidly in the mouth, treatment option in the management of acid-related
releasing the enteric-coated microgranules which are disorders, including gastric and duodenal ulcers and
swallowed with the patient’s saliva without water. Alter- gastroesophageal reflux disease, and the treatment or
natively, the tablet can be swallowed with a drink of prevention of gastroduodenal lesions induced by NSAIDs
water. Studies have shown that the bioavailability of [10]. Lansoprazole is also effective in combination with
LFDT is comparable to lansoprazole capsules, at both different regimens for H. pylori eradication and is in-
15 and 30 mg doses; the indications and recommended cluded in the first-line PPI-based options for this purpose
dosages for LFDT are therefore identical to lansoprazole [7, 8, 11–13].
capsules. The new formulation may be of particular ben-

© 2003 S. Karger AG, Basel Prof. Fabio Baldi

ABC 0012–2823/03/0672–0001$19.50/0 Department of Gastroenterology, S. Orsola-Malpighi Hospital
Fax + 41 61 306 12 34 Via Massarenti 9, I–40138 Bologna (Italy)
E-Mail karger@karger.ch Accessible online at: Tel. +39 051 6364180, Fax +39 051 4292369
www.karger.com www.karger.com/dig E-Mail Fabio.baldi@orsola-malpighi.med.unibo.it
 Lansoprazole fast disintegrating tablet (LFDT) is an patients are away from home and water is not readily avail-
orally disintegrating tablet and is a new, patient-friendly able, and in some patients with severe symptoms of odyno-
and more convenient formulation of lansoprazole which phagia or dysphagia, such as those with severe reflux
can be taken with or without water. LFDT, which has an esophagitis or esophageal stricture, or in elderly patients.
artificial strawberry flavoring, disintegrates rapidly in the
mouth and is swallowed easily with the patient’s saliva. It
is the first PPI that can be taken orally without water. This Lansoprazole Orally Disintegrating Tablet
formulation represents an improved alternative presenta-
tion for all patients requiring lansoprazole, offering the LFDT is an orally disintegrating tablet and is a new,
benefits of a choice of administration options. patient-friendly formulation that is easy to swallow and
LFDT maintains the same pharmacological properties can be taken orally with or without water. It has been
as lansoprazole capsules and can be taken by any patient developed to provide an alternative dosage form and to
who is currently prescribed lansoprazole. The ability to offer greater flexibility in the prescribing of lansoprazole.
take a tablet either with or without water will offer LFDT is supplied in blister packs in the same doses as
increased convenience and flexibility – particularly when lansoprazole capsules: 15 and 30 mg of lansoprazole per
patients are travelling – and may help to improve com- tablet.
pliance in some patients. In addition, LFDT may be suit- LFDT is the first PPI to be made available as an orally
able for certain groups of patients, such as those with dys- disintegrating tablet. Most enteric-coated tablets are for-
phagia associated with gastroesophageal reflux disease mulations of a single unit system; these tend to be small
[14], odynophagia or strictures, and the elderly or long- but generally there is a risk that the enteric coat can
term care patients [15]. become damaged during gastric emptying. The drug may
LFDT is available in Japan and the UK, and will soon then be exposed to acid, which can negatively influence
become available in the rest of Europe and the USA for absorption. A small crack or damage to a single unit sys-
use in all lansoprazole indications. This article summa- tem may therefore affect the entire dose. Multiple unit
rizes the development of LFDT and current clinical expe- systems have been developed to overcome this problem
rience with the formulation. Potential benefits of LFDT [16]. Common multiple unit systems include capsules
in certain groups of patients are also discussed. containing enteric-coated granules and tablets containing
enteric-coated granules. The granules are less likely to be
affected by gastric emptying due to their small size [17]; in
Lansoprazole Capsules addition, damage to a single granule will not affect the
entire dose. However, capsules and tablets are also con-
Lansoprazole is supplied for oral administration with sidered to be relatively large formulations. LFDT is an
water in capsules, which contain an enteric-coated improved formulation, containing much smaller micro-
granule formulation of lansoprazole. The enteric coating granules, which disintegrates rapidly in the mouth even
protects lansoprazole – which is acid labile – as it passes without water [unpubl. data].
through the stomach; the coating dissolves in the more
neutral conditions of the small intestine, where lansopra- Easy to Swallow
zole is absorbed. Absorption is rapid and relatively com- LFDT comprises enteric-coated microgranules of lan-
plete, with the maximum plasma concentration of lanso- soprazole compressed with an inactive, rapidly dispersing
prazole (Cmax) occurring within 1.5–2.2 h after oral dosing matrix to form a tablet. A pleasant strawberry flavor may
and absolute bioavailability ranging from 80 to 91%. help to stimulate saliva production. When the tablet is
Increases in Cmax and the area under the plasma concen- placed on the tongue and sucked gently it disintegrates
tration curve (AUC) of lansoprazole are linear over a dose rapidly in the mouth, releasing the enteric-coated micro-
range of 15–60 mg. Lansoprazole does not accumulate granules which are swallowed with the patient’s saliva
and its pharmacokinetics are unaltered by multiple dosing without water. Alternatively, the tablet can be swallowed
[7, 8]. with a drink of water.
Clinical trials conducted worldwide have demonstrated In two studies reported by Freston et al. [18], the aver-
that lansoprazole is well tolerated by most patients [8] and age disintegration times of LFDT without water were
is widely accepted as a capsule formulation. However, found to be 48 and 53 s for the 15- and 30-mg doses,
patient compliance with capsules may be affected when respectively.

2 Digestion 2003;67:1–5 Baldi/Malfertheiner

 Innovative Drug Delivery System
The properties of the microgranules determine the
characteristics of the acid resistance system and control
the in-vivo performance of LFDT. Each tablet is formed
with microgranules that are approximately 330 Ìm in
diameter – less than one third of the size of the granules in
lansoprazole capsules (approximately 1,100 Ìm). Their
reduced size allows for a smaller tablet, fast disintegration
and an acceptable feel in the mouth. The concentration of
enteric-coated microgranules in each tablet affects prop-
erties such as hardness, the time of tablet disintegration
and acid resistance. In a formulation study, the optimum
concentration of microgranules per tablet was found to be Fig. 1. Structure/composition of enteric-coated microgranules used
47.4% to maintain the quality of hardness, the time of to make LFDT (thickness of each layer is not to scale). 1 = Inert core;
2 = lansoprazole layer; 3 = under-coating layer – improves stability in
disintegration, acid resistance and buffer dissolution [un-
high humidity; 4 = 1st enteric-coating layer – improves stability of
publ. data]. lansoprazole; 5 = 2nd enteric-coating layer – prevents breakage of the
Unlike the granules in lansoprazole capsules, which enteric coats during tablet compression; 6 = 3rd enteric-coating lay-
have a core, a lansoprazole layer and a gastroresistant er – neutralizes taste of microgranule; 7 = over-coating layer – im-
enteric-coating layer, each LFDT microgranule comprises proves tablet hardness.
seven layers (fig. 1). The active lansoprazole layer sur-
rounds an inert core, followed by an inert under-coating
layer that improves stability in high humidity. Three
enteric-coating layers prevent dissolution in the stomach, 30 mg doses – such that its effect, in terms of efficacy and
improve stability, reduce damage during compression safety, will be the same. The indications and recom-
and neutralize the taste of the microgranule. An over- mended dosages for LFDT are therefore identical to lan-
coating layer improves the hardness of the tablet [19]. soprazole capsules.
In two studies reported by Freston et al. [18], the safety
Bioequivalent to Lansoprazole Capsules and bioavailability of LFDT taken without water were
When LFDT disintegrates in the mouth the microgran- compared with lansoprazole capsules after a single dose of
ules are swallowed with the patient’s saliva. Lansoprazole 15 or 30 mg. Each study enrolled 60 healthy adults and
is absorbed into the bloodstream after the enteric-coated utilized a randomized, single-center, two-period, cross-
microgranules dissolve in the neutral conditions of the over design with a 7-day washout interval. The mean plas-
small intestine. ma concentration profiles were comparable for LFDT
A bioavailability study has shown that lansoprazole is and lansoprazole capsules at both 15- and 30-mg doses
not absorbed via the oral mucosa during the short time (fig. 2). The 90% confidence levels for Cmax and AUC∞
that LFDT is dispersed in the mouth [unpubl. data]. In were within the 0.80–1.25 range (table 1), indicating that
this single-center, open, crossover study carried out in LFDT was bioequivalent to lansoprazole capsules at 15-
Japan, 12 healthy adult male volunteers were randomized and 30-mg doses. Both LFDT and lansoprazole capsules
to receive a single dose of LFDT 30 mg, which they either were safe and well tolerated.
swallowed with water or sucked (to aid dispersal in the Two single-center, open, crossover studies in Japan
oral cavity) and then spat out. A 7-day washout interval demonstrated bioequivalence between LFDT taken with-
separated the two regimens. Very low values were ob- out water and lansoprazole capsules, at both 15- and 30-
served for AUC0–24 and Cmax when LFDT was spat out mg doses [unpubl. data]. Twenty-four healthy adult males
(8.0 B 14.63 h W ng/ml and 6.8 B 10.52 ng/ml) compared were randomized to receive a single dose of LFDT (15 or
with LFDT swallowed with water (1,910.9 B 546.02 h W 30 mg), sucked and swallowed without water, or lansopra-
ng/ml and 978.8 B 401.62 ng/ml). In addition, almost zole capsule (15 or 30 mg), with a 7-day washout interval.
100% recovery of lansoprazole in the dispersed micro- The results for LFDT 15 mg without water versus lanso-
granules was observed. prazole capsule 15 mg were as follows: AUC0–24 values
Studies have shown that the bioavailability of LFDT were 1,105.3 B 1,101.40 vs. 1,136.2 B 1,186.29 h W ng/ml
is comparable to lansoprazole capsules – at both 15 and (geometric mean ratio 0.98; 90% confidence interval,

Lansoprazole Fast Disintegrating Tablet Digestion 2003;67:1–5 3

(Orally Disintegrating Tablets)
Fig. 2. Comparison of mean lansoprazole plasma concentration time Fig. 3. Comparison of dissolution profiles between LFDT 30 mg and
profiles between LFDT and lansoprazole capsule at 15- and 30-mg lansoprazole capsule 30 mg at buffer stage after a 60-min acid resis-
doses (data from Freston et al. [18]). tance test.

Table 1. Relative bioavailability of LFDT

versus lansoprazole capsules at 15- and Pharmacokinetic 15 mg 30 mg
30-mg doses (data from Freston et al. [18]) parameters
point estimate 90% CI point estimate 90% CI

Cmax 1.059 0.909–1.235 1.089 0.958–1.238

AUCł 1.042 0.932–1.164 0.992 0.900–1.092
AUC ∞ 1.033 0.928–1.150 0.988 0.900–1.083

0.89–1.07) and Cmax values were 474.1 B 254.04 versus Clinical Experience
442.7 B 231.71 ng/ml (geometric mean ratio 1.03; 90%
confidence interval, 0.87–1.22). The results for LFDT Patient Acceptability
30 mg dispersed versus lansoprazole capsule 30 mg were LFDT represents a new treatment option for all
as follows: AUC0–24 values were 2,216.5 B 1,270.16 ver- patients with acid-related disorders, offering a choice of
sus 2,223.6 B 1,203.07 h W ng/ml (geometric mean ratio administration. This may be especially useful for those
0.98; 90% confidence interval, 0.91–1.06) and Cmax val- with active life-styles who do not always have water avail-
ues were 992.8 B 384.34 versus 949.2 B 361.68 ng/ml able or those who find capsules and tablets difficult to
(geometric mean ratio 1.04; 90% confidence interval, swallow.
0.90–1.20). A patient acceptability study evaluated patient reac-
A second single-center, open, randomized, crossover tions to the taste of LFDT and their opinions on conve-
study in Japan has shown that the bioavailability of lanso- nience and the likelihood that they would request LFDT
prazole was similar after the administration of LFDT from their physician [unpubl. data]. General practitioners
30 mg with and without water [unpubl. data]. in the UK recruited 156 patients who were already pre-
LFDT has similar dissolution characteristics to lanso- scribed lansoprazole 30 mg, who were randomized to take
prazole capsules [unpubl. data] (fig. 3). LFDT 30 mg either swallowed with water or sucked and
swallowed without water for 2 days. Patients switched
their method of administration on days 3 and 4 and could
choose whether to take LFDT with or without water on
days 5–7.

4 Digestion 2003;67:1–5 Baldi/Malfertheiner

 The majority of patients found the flavor of the tablets Conclusion
acceptable (94 vs. 83% patients taking LFDT with and
without water, respectively). Similarly, the majority of LFDT is the first PPI that can be taken without water.
patients had no problems taking the tablets either with It is an innovative, patient-friendly formulation with a
water (91%) or without water (96%). The results indicated pleasant strawberry flavor, which disintegrates rapidly in
that while many patients would prefer to take LFDT with the mouth and is swallowed with the patient’s saliva with-
water when at home, many would also prefer to take out water. Alternatively, the tablet can be swallowed with
LFDT without water when on holiday, travelling, out a drink of water. LFDT is bioequivalent to lansoprazole
shopping or out with friends. In the subgroup of patients capsules and has identical indications and recommended
who chose to take LFDT without water on days 5–7, 88% dosages. The new formulation will offer greater flexibility
said they were very likely to ask their physician for the in the prescribing of lansoprazole, may improve patient
new formulation. All patients were confident that their compliance with treatment, and may be of particular ben-
medication would be effective, whether in the form of lan- efit to patients who have difficulty in swallowing and
soprazole capsules or LFDT taken with or without water. elderly patients. Future studies, comparing the two lanso-
prazole formulations in different clinical settings, will
provide more information on the real advantages offered
by LFDT.

References

1 Tolman KG, Sanders SW, Buchi KN, Karol 8 Bown RL: An overview of the pharmacology, 13 Pilotto A, Franceschi M, Leandro G, Bozzola
MD, Jennings DE, Ringham GL: The effects of efficacy, safety and cost-effectiveness of lanso- L, Fortnato A, Rassu M, Meli S, Soffiati G,
oral doses of lansoprazole and omeprazole on prazole. Int J Clin Pract 2002;56:132–139. Scagnelli M, Di Mario F, Valerio G: Efficacy of
gastric pH. J Clin Gastroenterol 1997;24:65– 9 Nakao M, Malfertheiner P: Growth inhibitory 7 day lansoprazole-based triple therapy for He-
70. and bactericidal activities of lansoprazole com- licobacter pylori infection in elderly patients. J
2 Fitton A, Wiseman L: Pantoprazole. A review pared with those of omeprazole and pantopra- Gastroenterol Hepatol 1999;14:468–475.
of its pharmacological properties and thera- zole against Helicobacter pylori. Helicobacter 14 Patti MG, Feo CV, De Pinto M, Arcerito M,
peutic use in acid-related disorders. Drugs 1998;3:21–27. Tong J, Gantert W, Tyrrell D, Way LW: Re-
1996;51:460–482. 10 Lai KC, Lam SK, Chu KM, Wong BCY, Hui sults of laparoscopic antireflux surgery for dys-
3 Hassan-Alin M, Andersson T, Bredgerg E, WM, Hu WHC, Lau GKK, Wong WM, Yuen phagia and gastroesophageal reflux disease.
Röhss K: Pharmacokinetics of esomeprazole MF, Chan AOO, Lai CL, Wong J: Lansopra- Am J Surg 1998;176:564–568.
after oral and intravenous administration of zole for the prevention of recurrences of ulcer 15 Friedel D, Fisher RS: Gastrointestinal motility
single and repeated doses to healthy subjects. complications from long-term low-dose aspirin in the elderly. Clin Geriatr 2000;8:30–43.
Eur J Clin Pharmacol 2000;56:665–670. use. N Engl J Med 2002;346:2033–2038. 16 Tateno M, Nakamura N: Phase I study of lan-
4 Swan SK, Hoyumpa AM, Merritt GJ: Review 11 Malfertheiner P, Megraud F, O’Morain C, soprazole (AG-1749) antiulcer agent – Capsule
article: The pharmacokinetics of rabeprazole in Hungin AP, Jones R, Axon A, Graham DY, form. J Clin Ther Med 1991;7:51–62.
health and disease. Aliment Pharmacol Ther Tytgat G; The European Helicobacter pylori 17 Tabata T, Kashihara T, Hirai S, Kitanori N,
1999;13(suppl 3):11–17. Study Group (EHPSG): Current concepts in Toguchi H: Effect of gastric pH on the absorp-
5 Howden CW: Clinical pharmacology of ome- the management of Helicobacter pylori infec- tion of a new antiulcer drug (lansoprazole) in
prazole. Clin Pharmacokinet 1991;20:38–49. tion – The Maastricht 2–2000 Consensus Re- the beagle dog. J Biopharm Sci 1991;2:319–
6 Richter JE, Kahrilas PJ, Sontag SJ, Kovacs TO, port. Aliment Pharmacol Ther 2002;16:167– 328.
Huang B, Pencyla JL: Comparing lansoprazole 180. 18 Freston JW, Chiu YL, Mulford DJ, Ballard
and omeprazole in onset of heartburn relief: 12 Misiewicz JJ, Harris AW, Bardhan KD, Levi S, ED: Comparative pharmacokinetics and safety
Results of a randomized, controlled trial in ero- O’Morain C, Cooper BT, Kerr GD, Dixon MF, of lansoprazole oral capsules and orally disinte-
sive esophagitis patients. Am J Gastroenterol Langworthy H, Piper D: One week triple thera- grating tablets in healthy subjects. Aliment
2001;96:3089–3098. py for Helicobacter pylori: A multicentre com- Pharmacol Ther 2003;17:361–367.
7 Matheson AJ, Jarvis B: Lansoprazole. An up- parative study. Lansoprazole Helicobacter 19 Shimizu T, Nakano Y, Tabata T, Hamaguchi
date of its place in the management of acid- Study Group. Gut 1997;41:735–739. N: 19th Symposium on Particulate Prepara-
related disorders. Drugs 2001;61:1801–1833. tions and Designs. October 2002, abstract A-
23.

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(Orally Disintegrating Tablets)