DESCRIPTION
SUMMARY OF THE INVENTION
The present invention is related to a pharmaceutical formulation of
Pantoprazole, which provides higher bioavailability and fast action than the
conventional Pantoprazole formulations.
BACKGROUND OF THE INVENTION
WO 2006/085723 relates to an oral pharmaceutical formulation formed by a
direct coating of an enteric layer containing polyethylene glycol as a plasticizer
on a core containing an acid-labile pantoprazole, and its manufacturing method.
The enteric coated oral pharmaceutical formulation of this invention, which
combines directly a core containing an acid-labile pantoprazole and an enteric
layer in the absence of an inert intermediate layer, is able to improve the
storage stability of the acid-labile pantoprazole and maximize the bioavailability
and oral absorption rates via preventing related substances from increasing.
WO 2002/026210 discloses a dosage forms of benzimidazole proton pump
inhibitors are prepared by enclosing one or several enteric coated compressed
cores in a capsule shell. The inventive formulations are stable and have higher
bioavailability of the active ingredient relative to pellet and granule containing
formulations.
US 2011/0250268 is related to novel oral compositions comprising an
irreversible gastric H+tK+-ATPase proton pump inhibitor (PPI) as a gastric acid
secretion inhibitor and one or more small carboxylic acid molecules as parietal
cell activators in the gastric lumen. Unexpectedly, the compositions of the
present invention are capable of enhancing the anti-acid activity of PPI in the
stomach. The pr-esent invention further relates to a method of using such
compositions to reduce gastric acid secretion in a mam~al.
US 2007/0196444 discloses a method of treating gastroesophageal reflux
disease (GERD), ulcers of the stomach or duodenum, or Zollinger-EIIison
Syndrome in a human, by administering pantoprazole sodium multi-particulates
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i
is described. The pantoprazole multiparticulates have a spheroid core of
pantoprazole or an enantiomer thereof, or a salt thereof, a surfactant, and a
disintegrant; a sub coat which is comprised of hydroxypropyl methylcellulose
(hypromellose) and water, an enteric coat on the subcoat, and a final seal coat
over the enteric coat, which is composed of hydroxypropyl methylcellulose
(hypromellose) and water.
OBJECTS OF THE INVENTION
The object of the present invention is to provide a pharmaceutical formulation
comprising proton pump inhibitor with more bioavailability compared to
conventional formulation.
Another object of the present invention is to provide a formulation which gives
rapid action compared to conventional formulation.
Yet another object of the present invention is to provide a stable formulation.
SUMMARY OF THE INVENTION
The invention is directed to a pharmaceutical formulation comprising Proton
Pump Inhibitors which provides a more bio-available and fast acting effect, that
results in faster onset of action and increased therapeutic efficacy.
DETAILED DESCRIPTION OF THE INVENTION
Proton-pump inhibitors (PPis) are a group of drugs whose main action is a
pronounced and long-lasting reduction of gastric acid production. They are the
most potent inhibitors of acid secretion. These drugs are among the most
widely-selling drugs in the world and are generally considered effective
The proton pump inhibitors are the benzimidazole derivatives which are acid
labile active pharmaceutical ingredients. These formulation are not stable in
acidic environment unless some measures are taken to protect the .formulation
from the deteriorating effects of acid in the stomach.
The examples of the acid-labile drugs, which are decomposed in the acidic
condition, include substituted benzimidazole derivatives such as rabeprazole,
omeprazole, pantoprazole, and lansoprazole.
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Mechanism of Acid Secretion
• Proton pump is a catalytic enzyme (H+-K+ATPase). It is present in the
canalicular membrane of Parietal Cells.
• Histamine, Acetylcholine and Gastrin are the three important stimuli for
acid secretion. When any one of these three stimuli bind to the parietal
membrane, the enzyme Proton Pump gets activated.
• Proton Pump gives out H+ ions in exchange of K+ ions. The H+ combine
with the Cl- to form HCI. Thus, there is a production of HCI which is
secreted by the parietal cells in the lumen of the stomach.
The present invention is formulated in a manner so that not only the formulation
is resistant from the gastric pH but also upon reaching in the intestine gives a
higher solubility, bioavailability and a faster onset of action.
The formulation according to this invention is formulated by using a variety of
excipients which helps in the faster and enhanced absorption.
The substance obtained for increasing the absorption and bio-availability may
be selected from the cyclodextrins (alpha, beta and gamma) and its derivatives
or the combination of the above. Particularly, the absorption enhancer may be
hydroxyethyl betacyclodextrin, Hydroxypropyl betacyclodextrin, beta
cyclodextrin or the sodium salt of sulfobutylether betacyclodextrin.
For faster action, the dissolution time of the formulation should be low. Thus, to
reduce the dissolution time, various super disintegrants are added to the
formulation.
Dissolution is essential for a drug to be absorbed through the biological
membranes into systemic circulation for therapeutic efficacy. Conventional
tablet formulations generally require rapid disintegration to aid drug dissolution.
Superdisintegrants are added to oral solid dosage formulations to facilitate
disintegration. Commonly used superdisintegrants such as crospovidone,
croscarmellose sodium, and sodium starch glycolate are highly efficient at low
concentration levels (2-5 w/w%) in the tablet formulation at facilitating the rate
and extent of tablet disintegration.
The super disintegrants used in the present formulation may be
Croscarmellose, Crosspovidone, Sodium Starch glycolate, and Alginic acid or
the combination of above.
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Apart from the above essential ingredients, the tablet may also contains other
ingredients which are u.sed for manufacturing conventional dosage forms.
The range of Proton pump inhibitors used in the present formulation can be
5mg to 80 mg, preferably 10 mg to 40 mg along with other pharmaceutical
acceptable excipients.
The present invention can be formulated, but not limited to, in the following
manner.
A) Following material is taken:
S.No Material Quantity
PREMIX MATERIALS
1 Pantoprazole sodium 2.260 Kg
2 Hydroxypropyl Betacyclodextrin 0.400 Kg
3 Starch 2.585 Kg
4 Sodium carbonate 0.350 Kg
5 Sodium Starch Glycolate 0.250 Kg
6 Sodium Lauryl sulphate 0.050 Kg
7 Colloidal Silicon Dioxide 0.025Kg
BINDER MATERIALS
8 HPMC 0.055 Kg
9 Polysorbate 0.100 Kg
LUBRICATION MATERIALS
10 Sodium Lauryl Sulphate 0.150 Kg
11 Colloidal Silicondioxide 0.050 Kg
12 Magnesium Stearate 0.150 Kg
13 Crosspovidone 0.500 Kg
COATING MATERIALS
14 Akoat 0.280 Kg
15 Procoat 0.925 Kg
B) Sifting
S.No Material Sieve#
1 Pantoprazole 40
2 Hyd roxypropyl betacyclodextrin 40
3 Starch 100
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4 Sodi um Carbonate 40
5 Sodi um Starch Glycolate 100
6 Sodi um Lauryl Sulphate 40
7 Colla idal Silicon diOxide 40
Take.pantopr
kg and mix
azole sodium 2.260 kg with Hydroxypropyl betacyclodextrin 0.400
manually for 20 minutes. Collect the sifted material in labeled
polythene bag lined HOPE xontainers.
PREPARATI ON OF BINDER
Take purified
0. 055 kg with
water in clean SS container and dissolve polysorbate 1 kg, HPMC
stirring to get transparent binder solution.
DRY MIXING
Transfer the
glycolate 0.2
sifted starch 2.585 kg, sodium carbonate 0.350 kg, sodium starch
50 kg, sodium lauryl sulphate 0.050 kg, colloidal silicon dioxide
Pantoprazole-HP betacyclodextrin mixture and mix at slow speed
10 minutes.
0.025 kg and
of impeller for
WETGRANU LATION
Add binders olution in the mixed material at slow speed over a period of about
10 minutes. A fter addition of binder solution, mix continuously
through imp eller and chopper at fast speed. If necessary, add additional
quantity of pu rified water to get the desired consistency.
WET MILLIN G
Pass the wet
forward orient
DRYING
granules through Multimill using screen of 8.0 mm at knives at
ation at s!ow speed.
Load the size d wet granules in FBD bowl and Air dry in FBD for 15 minutes.
ss intermittently in the FBD bowl. Then dry at 50° -55°G inlet air
and 40°C-45°C outlet temperature for 30 minutes or till to get the
Rake the ma
temperature
load NMT 3% w/w with intermittent raking (moisture at 90°C for 5 minutes).
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SIZING OF GRANULES
Pass the dried granules through sieve of mesh size 24. Pass the retained
granules through cad mill using screen of 1.0 mm . at knives at forward
orientation at slow speed.
SIFTING OF LUBRICANTS
S.No INGREDIENTS SIEVE SIZE
1 Sodium Laury! Sulphate 40
2 Colloidal Silicon Dioxide 40
3 Magnesium Stearate 40
4 Talcum 80
5 Cross povidone 40
BLENDING
Transfer the sized and dried granules and sifted Sodium Iaury! sulphate 0.150
kg, colloidal silicon dioxide 0.050 kg, Talcum 0.150 kg, crosspovidone 0.500 kg
into a cleaned Octagonal blender and blend for 1 0 minutes. Then add
magnesium stearate 0.075 kg and blend for 05 minutes.
COMPRESSION AND COATING
The mixture is then compressed and coated with the coating material.

We Claim:
1) A pharmaceutical formulation comprising Proton pump inhibitor and
bioavailability-enhancing substance along with pharmaceutically acceptable
excipients.
2) The proton pump inhibitor as claimed in claim 1 is preferably
Pantoprazole.
3) Pantoprazole as claimed in claim 2 is in the range 5mg to 80 mg,
preferably 10 mg to 40 mg.
4) Bioavailability enhancing substance as claimed in claim 1 may be
selected from cyclodextrins (alpha, beta and gamma) and its derivatives or
their combination.
5) Cyclodextrins as claimed in claim 4 may be hydroxyethyl
betacyclodextrin, Hydroxypropyl betacyclodextrin, beta cyclodextrin or the
sodium salt of sulfobutylether betacyclodextrin, preferably Hydroxypropyl
betacyclodextrin.
6) The pharmaceutically acceptable excipients as claimed in claim 1 are
selected from diluents, binding agents, disintegrants, and lubricants.
7) The formulation as claimed in claim 1 may be oral dosage formulation.