Download formulation and in vitro evaluation of bilayered buccal patches of a

FORMULATION AND IN VITRO EVALUATION OF BILAYERED BUCCAL
PATCHES OF A PROTON PUMP INHIBITOR
a)
BRIEF RESUME OF THE INTENDED WORK
NEED FOR THE STUDY:
Proton pump Inhibitors (PPIs) exhibit potent and long-lasting inhibition of gastric acid
secretion by selectively interacting with the gastric proton pump (K+ /H+ -ATPase) in the
parietal cell secretory membrane. However, the bioavailability of proton pump inhibitors
following oral administration is usually very low, since they degrade very rapidly in the
acidic environment of stomach and undergo hepatic first pass metabolism. To improve
the bioavailability of Proton pump Inhibitors, in particular by preventing gastric
degradation, various oral formulations of Proton pump Inhibitors such as enteric coated
granules and tablets have been developed1. PPIs are better antisecretory agents than H2
receptor antagonists (H2-RAs) 2, 3.
In this study, an attempt will be made to develop a PPI buccal adhesive patch to avoid
gastric degradation and first-pass metabolism in the liver. Absorption of drug from the
buccal mucosa and attachment of the patch with buccal mucosa without collapse are the
two prime considerations in the design of a conventional buccal adhesive patch
.However, an additional consideration in the case of PPI’s is the stability of PPI’s in
human saliva, since it is very unstable in acidic media4. Moreover, it has been reported
that a controlled release of the drug, over an extended period of time can be secured by
using various combination of polymers in a bilayered buccal adhesive patch5. Hence,
various formulations of a buccal adhesive patch of a PPI with bioadhesive polymers and
stabilizers, that may fulfill the above requirements, will be investigated.
Advantages of Buccal Patches:1. Rapidity of Action6.
2. Medications administered buccally bypass the first pass metabolism6.
3. Medications administered buccally directly enter systemic circulation without
undergoing gastrointestinal degradation6.
4. Buccal mucosa provides efficient blood supply and has relatively low enzymatic
activity7.
5. Moreover, the buccal mucosa is easily accessible and acceptable to patients; it
allows the patient to interrupt drug administration by simply removing the drug
delivery system7.
Hence, the present work is an attempt to formulate a bilayered mucoadhesive buccal
patch, containing proton pump inhibitor for inhibiting gastric acid secretion, bypassing
the first pass metabolism and to ensure better patient compliance.
6.2 REVIEW OF LITERATURE
Mucoadhesive buccal films of Ranitidine were formulated and evaluated by solvent
casting technique using polymers like hydroxy propyl methyl cellulose-15 cps and poly
vinyl pyrrolidone. The formulations of Ranitidine bioadhesive buccal were reported to
give controlled drug delivery, improve bioavailability and the dose of ranitidine could be
minimized by preventing the colonic degradation of ranitidine by colonic bacteria8.
Chitosan based sustain release mucoadhesive buccal patches containing verapamil
hydrochloride were formulated and evaluated using different ratios of chitosan and
polyvinylpyrrolidone (PVP K-30). It was concluded that Chitosan with PVP K-30 can
meet the ideal requirement for buccal devices, which can be good way to bypass the
extensive hepatic first pass metabolism and increase bioavailability9.
Mucoadhesive buccal patch of carvedilol formulated and evaluated by using two different
mucoadhesive polymers. Good results were obtained both in vitro and in vivo conditions
for films of HPMC E15 LV. It was concluded that development of bioadhesive buccal
formulation for carvedilol may be a promising one as the dose of carvedilol may be
decreased and hence side effects may be reduced10.
Mucoadhesive buccal patch of Propranolol hydrochloride formulated and evaluated by
using different ratios of chitosan and polyvinylpyrrolidone (PVP K-30). Finally it was
concluded that the optimized buccoadhesive patches of propranolol hydrochloride with
the combination of chitosan and PVP K-30 can meet the ideal requirements for buccal
devices, which can be a good way to bypass the extensive hepatic first pass metabolism11.
Buccal adhesive tablets of Omeprazole formulated and evaluated by using sodium
alginate and hydroxypropylmethylcellulose (HPMC). The results suggest that the oral
buccal adhesive tablet would be useful to deliver omeprazole1.
Carvedilol(CAR) buccal tablets using Methyl-β-cyclodextrin (CAR-MβCD) complex
,Carbopol 974P, sodium carboxymethylcellulose, lactose, PVPK30, talc and magnesium
stearate were formulated and evaluated for drug release, mucoadhesive strength and exvivo permeability. It was concluded that buccal tablet containing complexed CAR would
have improvement in bioavailability12.
Results from numerous comparative clinical trials and meta-analyses of these studies
have shown that Proton pump inhibitors (PPIs) are significantly more effective than H2
receptor antagonists for suppressing gastric acid secretion and healing duodenal and
gastric ulcers and erosive oesophagitis, and for the relief of acid-related symptoms. PPIs
are also significantly more effective than H2RAs or misoprostol for preventing and
healing NSAID-associated ulcer disease13.
It was concluded that the buccal mucosa was a promising delivery route for drugs that
need to avoid the gastrointestinal tract due to degradation by the gastric pH, intestinal
enzymes, or due to a substantial hepatic first pass effect. It can also be an alternative to
skin, pulmonary, or nasal delivery. The physiology of the buccal mucosa allows for the
penetration of active substances and due to its rapid cellular turnover and recovery, the
use of penetration enhancers is possible14.
Buccal
patches
of
famotidine
were
formulated
and
evaluated
by
using
Hydroxypropylmethylcellulose, Sodium carboxymethylcellulose, and polyvinyl alcohol
by using solvent casting method. The study successfully demonstrated that buccal patches
of famotidine reduced the dose and thereby decreased side effects15.
Mucoadhesive bilayered buccal devices comprising of a drug containing mucoadhesive
layer and drug free backing membrane were successfully formulated and evaluated ,
using mixture of drug (methotrexate) and sodium alginate alone or in combination with
sodium carboxy methyl cellulose, polyvinyl pyrollidine and carbopol 934 and backing
membrane(ethyl cellulose) by solvent casting technique5.
Bilayered buccal pacthes of felodipine were formulated and evaluated using hydroxyl
propyl methyl cellulose as primary layer and Eudragit RLPO as secondary layer by
solvent casting technique The results indicated that suitable bilayered buccoadhesive
patches with desired permeability could be prepared16.
A new validated, simple, rapid and reliable UV Spectrophotometry method for the
estimation of Omeprazole in blend & capsules formulations was reported 17.
6.3 OBJECTIVES OF THE STUDY
The present research work is an attempt to formulate a bilayered mucoadhesive dosage
form of PPIs by varying possible formulation variables and evaluation by process of
optimization.
This research work is an attempt to
1. Formulate a bilayered mucoadhesive dosage form containing a PPI.
2. Evaluation for the following
i.
Film weight and thickness.
ii.
Surface pH of the patches.
b)
iii.
Folding endurance.
iv.
Tensile strength of the patches,
v.
Drug Content Uniformity of patches.
vi.
In Vitro Release Studies of PPI patches.
vii.
In Vitro Bioadhesive Test.
viii.
Percentage moisture absorption.(PMA)test.
ix.
Percentage moisture loss.(PML)test.
x.
Swelling percentage.(%S)test.
MATERIALS AND METHODS
7.1 SOURCE OF DATA:
Data on drugs and dosage forms will be
collected from Drug Information Center,
standard books, physicochemical database and literature search from
 Scientific journals and related articles.
 Internet facilities.
 Krupanidhi College of pharmacy library.
 Publication and Journals of Pharmacy.
7.2 METHOD OF COLLECTION OF DATA:
The data on physicochemical and pharmacokinetic properties
of the drug will be
collected from drug information center, various standard Books, journals, websites and
other sources like research literature databases such as Medline, Science Direct etc.
The experimental data will be collected from study of the drug; its formulation, through
investigation of the process and product variables in the laboratory of Krupanidhi College
of Pharmacy, Bangalore-35.
c)
REFERENCES
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Han GC, Hee JJ, Soon CY, Dal CR, Kyung ML, Hee JH, et al. Formulation and
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