A REVIEW ON ACID REFLUX THERAPY THROUGH BUCCAL ROUTE

Anjali Kansal* and Sunil Kumar Batra

Deptt. of Pharmaceutics, Hindu College of Pharmacy,

Sonepat – 131001, Haryana, India.

ABSTRACT

Gastroesophageal reflux disease, or GERD is a condition that develops when gastric acid
from the stomach travels upto the esophagus. The acid in the esophagus causes heartburn
and other symptoms, as well as possible tissue damage. GERD is often be treated with
medications before attempting other lines of treatment. H2 blockers Proton pump inhibitors
(PPI) are one of the main pharmaceutical treatment options for people with GERD. Other
options include Proton pump inhibitors (PPI), antacids, prokinetics.
Oral route is the most preferred route for drug administration but bioavailability of many
GERD treatment drugs, especially proton pump inhibitors is very low since these degrade
very rapidly in acidic environment of stomach and undergo hepatic first pass metabolism.
Moreover, many pediatric, geriatric patients and persons with dysphagia face difficulty in
swallowing a tablet. Swallowing becomes even more challenging for patient suffering from
GERD. To overcome these drawbacks, buccal mucosa can be used as a route for the drugs
meant for GERD treatment. Buccal route is also suitable for reducing the frequency of
dosage administration by using controlled release approach.
The present article gives a brief view on various research studies undertaken in the area of
buccal delivery system on GERD treatment drugs to improve bioavailability and patient
compliance.

Keywords: GERD, Buccal Route, H2 Blockers, Proton pump inhibitors

INTRODUCTION

Heartburn is one of the common symptoms of gastro-esophageal reflux. A specific muscle;

the lower esophageal sphincter (LES) is located at the lower end of the food pipe
(esophagus). This sphincter opens during swallowing to allow food to pass into the stomach
and then quickly closes to prevent the movement (reflux) of food and stomach acid back
into the esophagus. If the LES doesn't close properly or if it opens too often, acid produced
by stomach can move up into the esophagus. People will experience burning sensation or
chest pain when excessive amounts of acid reflux into the esophagus. The sensation
radiates up from the stomach to the mid-chest or throat. This is known as heartburn. It is
also called acid regurgitation.40

Buccal delivery is the administration of the drug via buccal mucosa to the systemic
circulation. The mucosal lining of buccal tissues provides a much milder environment for
drug absorption. Buccal route of drug delivery offers distinct advantages like reduced first-
pass metabolism, increased bioavailability, patient compliance, rapid onset of action, usage
of the dosage form in accordance with need, ease of administration, prevention of drug
degradation in gastrointestinal environment and comparatively less susceptibility to
enzymatic activity. Moreover, it does not require swallowing of the drug, which is most
suitable for pediatric as well as geriatric patients. Hence, mucoadhesive dosage forms in the
form of tablets, gels, and patches are prepared for buccal route system.39,41

Buccal mucoadhesive systems adhere and remain on the oral mucosa to improve drug
delivery and to release their drug content gradually. These drug delivery systems release the
drug in a controlled manner. Buccal system uses the property of bioadhesion of certain
water soluble polymers which turn into adhesive on hydration. These systems improve the
efficiency of a drug by maintaining the drug concentration between the therapeutic and
toxic levels and by targeting and localization of a drug at desired site. Mucoadhesive
controlled-release devices provide drug release in an unidirectional way towards the
mucosa.42

A number of acid reflux therapy buccal delivery system have been introduced into the
pharmaceutical market. The permeation of hydrophilic drug through membrane is one of
the major limiting factors for the development of bioadhesive buccal delivery devices. The
epithelium that lines the buccal mucosa is a main barrier for the absorption of drugs. In
order to improve buccal absorption, several approaches have been introduced. Increased
permeation of the drug through the buccal membrane and prevention of the drug
degradation by enzymes was achieved by changing the physicochemical properties of the
drug. Alternatively, improving the bioadhesion and release characteristics of buccal delivery
devices increases the amount of drug available for absorption. The incorporation of
absorption enhancers to the buccal formulation is one interesting approach. Substances
that facilitate the permeation through buccal mucosa are referred as permeation
enhancers.1

This review is an attempt to compile various research studies undertaken in the area of
buccal delivery of drugs used in the treatment of GERD reported in various pharmaceutical
Journals.

WORK DONE ON BUCCAL DELIVERY SYSTEM OF ACID REDUCING DRUGS

AMOXICILLIN TRIHYDRATE
Amoxicillin is a broad-spectrum, semisynthetic amino-penicillin antibiotic with bactericidal
activity and is commonly used to treat bacterial infections in the body such as gonorrhoea,
skin infections, tooth infections, tonsillitis, ear infections, inflammatory illness of
the lung, bronchitis, urinary tract infections, and other forms of bacterial infections.
Amoxycillin Trihydrate should be taken exactly as prescribed by your doctor. If a dose is
missed, it should be taken as soon as it is remembered. However, if it is almost time for the
next scheduled dose, the missed dose should be skipped to avoid the potential of an
overdose. Overdose should be avoided. If pain, muscle spasm, twitching, weakness, loss of
feeling in the fingers or toes, confusion, agitation, seizures or coma is experienced,
immediate medical attention should be seeked. Amoxycillin Trihydrate show negative drug
interactions with some medications like antibiotics, methotrexate, probenecid
and allopurinol.2

Biswas and Majee3 studied the kinetics of drug release pattern from buccal tablets of
amoxicillin trihydrate prepared with modified gum karaya. On increasing the concentration
of modified gum karaya, swelling index is also increased. When in vitro release pattern of
Amoxicillin trihydrate from the buccal tablets in relation to change in concentration of
modified gum karaya is studied, a significant variation exists. The linearity of drug release
pattern ascertain that drug release from these formulation could follow zero order kinetics.
It was confirmed by Korsmeyer-Peppas exponential equation, Mt/Mα =Ktn , where n is the
diffusional exponent, which characterizes the drug transport mechanism. Kopcha
mathematical model further confirmed it. After evaluating diffusion and erosion terms, a
predominance of diffusion relative to swelling or erosion throughout the entire test period
is resulted. The greater rate of polymer swelling is due to the high water affinity of the gum,
which is reflected in the drug diffusion mechanism.

Boateng J et al.,4 formulated solvent casted mucosal films by combining sodium alginate
(SA), carboxymethyl cellulose (CMC), and carrageenan (CAR). The drud loading capacity of
amoxicillin and paracetamol was increased many folds. Glycerol (GLY) was chosen as
plasticiser as it is suitable plasticiser for hydrophilic polymers such as CMC and SA. The drug
was first dissolved in the deionised water before addition of the plasticizer and polymers to
form more uniform and homogenous films. The three polymers used are hydrophilic with
several OH groups available for interacting with the glycerol, which acts by reducing the
interchain interactions and ultimately increasing the specific volume with a resultant
decrease in glass transition. In case of single polymers, there is formation of weak and sticky
films which are not ideal. Because relatively high amounts of GLY generally result in
excessive plasticization. The characterization of films were done using scanning electron
microscopy (SEM), folding resilience, X-ray powder diffraction, mucoadhesivity, swelling
capacity, and drug dissolution studies. The maximum loading for both drugs was achieved at
40% (paracetamol) and 26.3% (amoxicillin), and this was possible using combinations of
CAR:CMC: GLY(1 : 2 : 3 for paracetamol) and SA: CMC: GLY(5 : 3 : 6 for amoxicillin). The two
formulations showed differences in adhesive and hydration properties which are expected
to influence their mucoadhesive performance on the buccal surface but this requires further
investigations.

METRONIDAZOLE
Metronidazole is an antibiotic and antiprotozoal medication that is used to treat a wide
variety of infections. It is effective against anaerobic bacteria and certain parasites.
Metronidazole may also be used with other medications to treat certain stomach/intestinal
ulcers caused by a bacteria(H. pylori). Metronidazole is usually given for up to 10 days. It is
available in different strengths like : 500 mg; 250 mg; 375 mg; 750 mg; 500 mg/100 mL;
benzoate; 50 mg/mL; 100 mg/mL. The elimination half-life of metronidazole is 7-8
hours, The peak concentrations were observed 1.2 - 1.3 hrs after the administration of
tablets. The bioavailability of the tablets is 80.4 per cent. Metronidazole should not be taken
if disulfiram (Antabuse) has been taken within the past 2 weeks. Foods or medicines
containing propylene glycol should not be consumed while taking metronidazole.2
Amal Hassan El-Kamel5 formulated metronidazole benzoate mucoadhesive film for
treatment of periodontal diseases. Periodontal diseases are localized infections and
inflammatory conditions that are associated with anaerobic Gram-negative bacteria and
affect teeth-supporting structures. The aim of current periodontal therapy is to remove the
bacterial deposits from the tooth surface. Mucoadhesive micromatricial chitosan/poly (ὲ-
caprolactone) films and chitosan films were prepared. Thermal behaviour, morphology, and
particle size measurements were used to evaluate the prepared films. The developed
mucoadhesive film was satisfactory in terms of drug release, and mechanical and
bioadhesion properties. In addition, it allowed local delivery of the drug in a concentration
higher than the metronidazole MIC against anaerobic bacteria responsible for periodontal
diseases, over 6-hour periods with high PD efficacy. Moreover, by comparing the applied
dose to the reported systemic dose (20 vs 300 mg), a remarkable reduction of the single
drug dosage was achieved (~15-fold). In addition, the proposed formulation is not to be
professionally delivered, so it requires little or no patient compliance for success.

Perioli L et al.,6 formulated mucoadhesive buccal tablet of metronidazole using HEC and
carbomer 940 in 2:2 ratio for periodontal disease treatment. The new mucoadhesive tablet
formulated allows a good metronidazole local sustained release in the oral cavity for 12 h
together with a remarkable reduction of the daily drug dosage (more than 15 folds) if
compared to traditional systemic therapies (40 mg pro-die vs. 600 mg). These results
guarantee the achievement of therapeutic concentration in the action site, the decrease of
drug side effects and the improvement of patient’s compliance. Therefore, such formulation
looks very promising for clinical application. Furthermore, these findings demonstrate that
the target of our research was fully achieved either in term of dose reduction or in providing
a suitable formulation.

Patel B et al.,7 formulated bioadhesive buccal tablets of metronidazole by direct

compression method. Metronidazole was choosen as model drug with an aim to develop
buccal drug delivery system having characteristics like; small size, flexibility & adaptability to
the mucosa, no irritation, and no discomfort as well as to develop a sustained release
system for 12 hrs. The prepared formulation were evaluated for various parameters like
hardness, thickness, average weight, swelling index, surface pH, mucoadhesive strength,
drug content, % cumulative drug release. The optimized formulation was subjected to
stability study for 1 month. In preliminary batches 3 polymers were used in combinations,
from the obtained evaluation data of preliminary batches polymers (Carbopol 934 P and
NaCMC) were selected for further factorial design batches, from the evaluation parameters
data, it had been seen that the Batch F6 Showed good results from all batches. Batch F6
show hardness 3.82 kg/cm2, thickness 1.69 mm, friability 0.32%, surface pH 6.42, average
weight 124.5 mg, mucoadhesive strength 31.8 gm and drug content 98.45%. It also gives
maximum drug release up to 97.306 % in 12 hrs from all other batches.
Sylvester Okhuelegbe Eraga et al.,8 formulated bioadhesive tablets of metronidazole from
gellan gum and gelatin dispersions by wet granulation. The bioadhesive strengths of the
dispersions and tablets were determined using the coated bead and tensiometric methods,
respectively. Tablet parameters evaluated were weight uniformity, friability, hardness,
disintegration time, content of active, swelling index and tablet erosion. Release studies
were carried out in simulated intestinal and gastric fluid. All batches of tablets met
compendial specifications with regard to weight uniformity, friability, hardness and content
of active except disintegration times. Tablets prepared with gelatin alone had the highest
swelling index and bioadhesive strength (40 %, 5 h and 0.253 Nm-1) while those prepared
with gellan gum alone had the highest percentage tablet erosion and least bioadhesive
strength (15 % and 0.085 Nm-1). It was concluded that Gelatin increased the bioadhesive
strength of gellan gum. Gellan gum-gelatin ratios of 1:2 and 1:4 were the optimum
combinations and were superior in the formulation of metronidazole tablets. The
hydrophilic bioadhesive polymers enhanced the steady release of the drug.

Cimetidine
Cimetidine is a histamine H2-receptor antagonist. Histamine H2-antagonists inhibit the
action of histamine on the acid-producing cells of the stomach and reduce stomach acid. It
is mainly used in the treatment of heartburn and peptic ulcers. Bioavailability of cimetidine
is about 60% based on the plasma concentration data. Absorption is not significantly
impaired by the administration of food or antacids. Propantheline increases peak blood
levels of cimetidine, probably by delaying gastric emptying and transit time. Inone study,
simultaneous administration of high-potency antacid (150 mmol) in fasting subjects has
been reported to decrease the absorption of cimetidine. At steady-state, the volume of
distribution of cimetidine is 80% of body weight. The plasma clearance value of cimetidine,
495 ml/min, is mainly due to renal clearance (293 ml/min). The elimination half-life is
approximately 2 hours.2

S. Manikandan9 formulated and evaluated buccal patches of cimetidine using Hydroxy

Propyl Methyl Cellulose (HPMC), SCMC, Poly Vinyl Alcohol (PVA). The polymers were
dispersed in ethanol and water and glycerol served the purpose of plasticizer. The prepared
films were evaluated based upon their physical characteristics like thickness, weight, folding
endurance studies were performed. Thickness of the formulation varied from 0.27± 0.036 to
0.34±0.022 mm. Weight of the formulated buccal films ranges from 208.6±1.52 to 218.4±
2.08 mg. Folding endurance ranged from 280±3.6 to 315±6.3.The percent drug content
among all the formulations ranged from 92.75± 0.476 to 98.96± 0.057. The cumulative drug
release values showed a gradation from 88.5 % to 99.2 % showing the better controlled
release properties. The correlation coefficient values (R2) indicate the kinetic of drug release
was zero order and the mechanism of drug release was by peppas model indicates the
Fickian transport evidenced with diffusion exponent values (n). The optimized films showed
no significant changes in the % drug remaining after the stability studies for 3 months. The
formulations of cimetidine buccal film is satisfactory as controlled drug delivery.
Bioadhesive film improves the bioavailability, minimizes the dose of cimetidine and prevents
the colonic degradation of cimetidine by colonic bacteria.

Famotidine
Famotidine is a thiazole ring containing H2 blocker which binds tightly to H2 receptors and
exhibits longer duration of action despite an elimination t 1/2 of 2.5-3.5 hr. Some inverse
agonistic action on H2 receptors (in the absence of histamine) has been demonstrated. It is
5-8 times more potent than ranitidine and antiandrogenic action is absent. Because of low
affinity for cytochrome P450 and the low dose, drug metabolism modifying propensity is
minimal. The oral bioavailability of famotidine is 40-50% and it is excreted by the kidney,
70% in the unchanged form. Dose: 40 mg at bed time or 20 mg BD (for healing); 20 mg at
bed time for maintenance; upto 480 mg/day in ZE syndrome; parenteral dose 20 mg i.v. 12
hourly.2

Alagusundaram, et al.,10 prepared buccoadhesive bilayer tablets of famotidine by direct

compression method using bioadhesive polymers like sodium alginate, Sodium Carboxy
Methyl Cellulose, Hydroxy Propyl Methyl Cellulose-K100M, PVP-K30. Ethyl Cellulose was
chosen as a backing layer because of its low water permeability and flexibility in the buccal
environment. The prepared buccoadhesive bilayer tablets were evaluated for thickness,
weight variation, hardness, friability, swelling index, surface pH, ex vivo buccoadhesive
strength, in vitro, in vivo drug release, ex vivo permeation studies and drug content. The
distinguishable differences in the results were shown to be dependent on characteristics
and composition of bioadhesive materials used. The best formulation was showing good
stability in natural human saliva and accelerated conditions. The P-value statistically
significant at <0.05. Ex vivo mucous irritation by histological examination reveals, the
administration site of buccal tablet over the buccal mucosa did not cause any irritation,
ulceration, inflammation and redness, and it resembles to controlled buccal mucosa. Good
correlations were observed between in vitro and in vivo drug release, with a correlation
coefficient of 0.996. Drug diffusion from buccal tablets showed apparently zero order
kinetics and release mechanism was diffusion controlled after considerable swelling.

Manish et al.,11 developed mucoadhesive buccal films of famotidine using sodium carboxy
methyl cellulose (SCMC),hydroxyl propyl methyl cellulose, and polyvinyl alcohol by solvent
casting method. Fourier transform infrared (FTIR) Spectroscopy did not show any evidence
of physicochemical interactions between drug and polymers. The famotidine patches were
examined for their physical characteristics like thickness, weight variation, drug content
uniformity, surface pH, folding endurance, tensile strength and mucoadhesion strength. In
vitro release studies were conducted for famotidine patches in phosphate buffer (pH, 6.6)
solution. Patches exhibited drug release in the range of 72.58 to 91.91% in 20 min. Superior
results were obtained both in vitro and in vivo conditions for famotidine films. The buccal
release of famotidine from patches in healthy rabbits showed a significant improvement.
The results can be extrapolated to the human beings as the structure and permeability of
buccal membrane of rabbits is similar to that of human beings. Hence the development of
bioadhesive buccal films for famotidine is good choice as the dose of famotidine is
decreased, bioavailability is increased and side effects are reduced.

Mohammed Imaduddin et al.,12 formulated buccoadhesive films of famotidine using

hydroxy propyl methyl cellulose -15cps (HPMC), carbopal (CP) and poly vinyl pyrrolidine
(PVP) by solvent casting method. Fourier transform infrared (FTIR) Spectroscopy did not
show any evidence of physicochemical interactions between drug and polymers. The
famotidine films were examined for their physical characteristics like weight variation,
thickness, drug content uniformity, surface pH, folding endurance, swelling percentage,
percentage moisture absorption (PMA), percentage moisture loss (PML), water vapour
transmission rate (WVT), mucoadhesion strength, Ex-vitro permeation studies. In vitro
release studies for famotidine films were conducted in phosphate buffer (pH, 6.8) solution.
The withdrawn solutions at predetermined times were thereafter analysed
spectrophotometrically at 289 nm. A Total number of 8 formulations were prepared and In
vitro drug release study of all the formulations showed that, from the formulation F8 the
drug was released approximately upto 99.8% in 45 minutes. Hence formulation F8 was the
best obtained formulation in the above study. Data of in-vitro release were fit into different
equations and kinetic models to explain the release kinetics of famotidine from the buccal
films. The kinetic models used were a Zero order equation, First order equation, Higuchi’s
model and Peppa’s models. The correlation coefficient values (R2) indicate that the drug
release was following zero order release kinetics. The mechanism of drug release was by
peppas model indicates the super case II transport evidenced with diffusion exponent
values (n) i.e > 0.89. Finally it may be concluded that the successful formation and
optimization of fast dissolving films of famotidine was done using HPMC CP and PVP. Hence
Famotidine can be conveniently administered orally in the form of films.

Karimunnisa Shaik. et al.,13 developed buccal tablets of famotidine by direct compression

method. The optimized solid dispersion containing guar gum 1:6 ratios is selected for the
formulation of buccal tablets using three bioadhesive polymers i.e., sodium carboxy methyl
cellulose, sodium alginate and carbopol 934P. Prepared famotidine buccal tablets were
evaluated and based on dissolution studies F2 is considered as optimized formulation of
improving solubility of drug. Again solid dispersions were prepared with drug, guar gum and
sodium lauryl sulphate (as penetration enhancer) in 0.5, 1, and 1.5% to increase drug
permeability. By using solid dispersion containing SLS, buccal tablets were prepared and
evaluated for Weight variation, Thickness, Hardness, Swelling studies, Bioadhesive strength,
invitro Dissolution and Ex-vivo Diffusion studies. The sustained drug release and permeation
was obtained for the formulation containing 1% SLS as permeation enhancer, sodium
alginate and carbopol 1:2 ratio as bioadhesive polymers and the % release was 93.58%,
diffusion was 89.92% after 8 hours. The developed buccal drug delivery of famotidine buccal
tablets was one of the alternative routes of administration to avoid first pass metabolism
and to improve bioavailability through buccal mucosa. It is capable of releasing the drug for
sustained action to reduce the need of frequent administration and improve patient
compliance.

Ranitidine
Ranitidine is a nonimidazole H2 blocker with a furan ring. It is 5 times more potent than
cimetidine. Dose of 300 mg or 150 mg given night before and in the morning benefit by
raising pH of gastric juice; may also reduce its volume and thus chances of regurgitation.
Parenteral dose-50 mg i.m. or slow i.v. inj. every 6-8 hr (rapid i.v. injection can cause
hypotension), 0.1-0.25 mg/kg/hr by i.v. infusion has been used for prophylaxis of stress
ulcers. The t1/2 of ranitidine is 2-3 hr.2

Lohani et al.,14 prepared buccoadhesive films of Ranitidine by solvent casting technique

using polymers hydroxy propyl methyl cellulose K15 (HPMC K15) and carbopol 934P. The
films exhibited controlled release more than 12 h. An increase in carbopol 934P content was
associated with a corresponding decrease in the drug-release rate. The drug release was
observed to be sustaining with increasing the incorporation of higher amount of Carbopol
934P in patch A2. This could be due to the extensive swelling of the polymers, which created
a thick gel barrier for drug diffusion. Formulation containing Carbopol and HPMC in
combination shows better release profile then used alone.
Dixit et al.,15 formulated buccal film of Ranitidine Hydrochloride using Sterculia foetida gum
as mucoadhesive natural polymer and carbopol 934P as synthetic polymer by solvent
casting technique. The prepared films were evaluated or characterized based upon their
physicochemical characteristics like surface pH, percentage moisture absorbance,
percentage moisture loss, swelling percentage, water vapour transmission, thickness,
weight, folding endurance and drug content. The formulation containing Ranitidine HCl,
Sterculia foetida gum, Carbopol 934P in ratio 1:2:0.4 has shown very good physical stability,
excellent mucoadhesive strength, good stability and prolonged drug release. These
polymers in combination improve the bioavailability of the drug by circumventing hepatic
first pass metabolism and have wider prospects to be incorporated in buccal films as
mucoadhesive drug delivery system.

M. Alagusundaram et al.,16 prepared ranitidine buccal films by solvent casting technique.

Polymers of hydroxy propyl methyl cellulose-15 cps and poly vinyl pyrrolidone (PVP) were
dispersed in ethanol and dichloromethane and 30 % w/w propylene glycol which served the
purpose of plasticizer as well as penetration enhancer. The prepared buccal films were
evaluated based upon their physico chemical characteristics like swelling percentage,
thickness, weight, surface pH, Percent Moisture Absorption, Percent Moisture Loss, , Water
Vapour Transmission, folding endurance and drug content. The formulation R5 containing 2
% HPMC and 1 % PVP exhibit best matrix controlled release and mucoadhesive
performance. The zero order kinetic of drug release was indicated by correlation coefficient
value (r). The ranitidine buccal film was found to be right and suitable candidate for
therapeutic use. Good results were obtained both in physico chemical characteristics and in
vitro studies.

Esomeprazole
Esomeprazole irreversibly inhibits the gastric parietal H+/K ATPase enzyme involved in the
production of hydrochloric acid in the stomach. It acts as proton pump inhibitor having
biological half life of 1-1.5 h, with peak plasma concentration of 0.5-1.0 mg/l within 1-4
hours. The oral bioavailability of esomeprazole is 50-90 % depending on the dose and the
frequency or repetition of dose12. It undergoes hepatic metabolism and protein binding is
97 %. Approximately 80 % of the administered dose of esomeprazole is excreted as
metabolites in urine and the remaining 20 % is excreted in faeces. Its volume of distribution
is 16 litres13. The stability of esomeprazole decreases with a corresponding decrease in the
pH of the media. Hence, the exposure of esomeprazole to the acidic contents of the
stomach leads to significant degradation of the drug and result in reduced bioavailability. It
is used to treat peptic ulcer disease, gastroesophageal reflux disease, erosive esophagitis,
Ulcerative colitis, heart burn, dyspepsia and Zollinger-Ellison syndrome. Esomeprazole has
very short biological half life of about 1.5 hr.2

Shah Harsh Kirankumar et al.,17 formulated esomeprazole buccal patches by solvent casting
technique using different proportions of bioadhesive polymers, HPMC 50cps, Eudragit RL-
100, plasticizers glycerol and penetration enhancer tween-80.The buccal patches were
designed to prolong adhesion to buccal cavity and thus to increase the bioavailability of the
drug and half life. The physico-chemical compatibility of drug and polymers was studied by
FT-IR spectroscopy. The results suggested no physicochemical incompatibility between the
drug and the polymers. Unidirectional release was achieved by preparing composite patches
with backing membrane. The patches were characterized on the basis of their physical
characteristics like weight uniformity, thickness, swelling studies, folding endurance, surface
pH, bioadhesive performance, in vitro drug release and ex vivo drug diffusion.

Nanne Chandrakanth18 formulated bioadhesivebuccal tablets of esomeprazole magnesium

by using carbpol-934 (CP), hydroxy propyl Methyl cellulose K4M (HPMC K 4M), hydroxy
propyl Methyl cellulose E5 (HPMC E5) as bioadhesive polymers to impart mucoadhesion in
drug: polymer ratio of 1:1, 1:1.25, 1:1.5 and ethyl cellulose to act as an impermeable
backing layer. Buccal tablets were evaluated forhardness, thickness, content uniformity,
weight uniformity, swelling index, surface pH, ex-vivo mucoadhesion strength, ex-vivo
mucoadhesion time, in-vitro drug release and in-vitro drug permeation. The buccal bilayered
tablet showed slow release of drug along increased bioavailability. The ex-vivo drug release
of F8 formulation showed 84.28±0.76 in 7hrs. The mechanism of drug release was found to
be following zero order along obeying peppas and Hixson crowell release kinetics, which
was perfectly suitable for a controlled release formulation, stability of the drug in the
optimised buccal tablets found to be stable in human saliva for 6 hours. FTIR studies show
no interaction between drug and polymers. The development of bioadhesive buccal drug
delivery of esomeprazole magnesium tablets was one of the alternative routes of
administration to avoid first-pass effect and provide prolonged release. Buccal tablets
reduced the need of frequent administration and enhanced patient compliance. Hence, it
can be inferred that there is an ample scope for the development of buccal bioadhesive
dosage forms of Esomeprazole magnesium on further research.

V. Jayasankar Reddy and K. Ramesh Reddy19 formulated buccoadhesive tablets of

esomeprazole by direct compression method using Hydroxy Propyl Methyl Cellulose
(HPMC), Sodium Carboxy Methyl Cellulose (SCMC), Micro Crystalline Cellulose and Carbopol
934P along with Ethyl Cellulose (EC) as an impermeable backing layer. Mucoadhesion
increases the intimacy and duration of contact between drug containing polymer and a
mucous surface. It is believed that the mucoadhesive nature of the device can increase the
residence time of the drug in the body. The bioavailability of the drug is improved because
of the combined effects of the direct drug absorption and the decrease in excretion rate.
Increased residence time and adhesion leads to lower drug concentration and lower
administration frequency to achieve the desired therapeutic outcome. Tablets were
evaluated by using micrometrics properties, post formulation characters such as hardness,
thickness, friability, content uniformity, Ex vivo mucoadhesive strength and in-vitro
dissolution studies. The physico-chemical compatibility of drug and polymers was studied by
FT-IR spectroscopy. The results suggested no physicochemical incompatibility between the
drug and the polymers. The prepared tablets were characterized for their physico-chemical
characteristics, surface pH, swelling index and results were within the limits of
pharmacopoeia in allformulations(F1-F12). The formulation F4 consisting of Esomeprazole
(20mg), carbopol (60mg), HPMC (20mg), microcrystalline cellulose (48mg), ethyl cellulose
(50mg), magnesium stearate (2mg) was selected as best formulation. Various
physiochemical parameters tested for this formulation showed good results. Good
correlation was observed between in-vitro and in- vivo drug release profiles. Formulation F4
was stable and non-significant from P value obtained by one way ANOVA. Thus
Esomeprazole is suitable candidate for oral controlled drug delivery via buccoadhesive
tablets. Further work is recommended to support its efficacy claims by long term
pharmacokinetic and pharmacodynamic studies in human beings.

Nagarani et al.,20 formulated Esomeprazole mucoadhesive buccal tablets by direct

compression technique using natural polymers like guargum and mucoadhesive polymers
like hydroxypropylmethylcellulose K 100 M, Carbopol 934, HPMC K 15 M. Mucoadhesive
tablets in oral cavity is going to extend the release upto 6-7 hrs and also going to avoid the
acidic environment in which the is unstable. The prepared tablets were evaluated for
different physical parameters and dissolution study were performed in two dissolution
mediums like pH 6.8 and pH 7.4 phosphate buffer solution.

Patel Deval21 formulated bilayered buccal tablets of esomeprazole by direct compression

method using POLYOX WSR 303 (30%) as a bioadhesive polymer and HPMC K15M (20%) as a
release modifying polymer and ethyl cellulose as backing layer. Bioadhesive bilayer buccal
tablets were evaluated for weight variation, thickness, hardness, friability, surface pH,
mucoadhesive strength, mucoadhesive time, swelling index, in vitro drug release. The
swelling index of tablet increased with increasing amount of HPMC K15M. Stability studies
indicated that there are no significant changes in drug content and in vitro dissolution,
bioadhesive strength and swelling index. The formulation consisting of esomeprazole (20
mg), HPMC K15M (12 mg), POLYOX WSR 303 (18 mg), Microcrystalline cellulose 102 (8.8
mg), Mg. stearate (0.6 mg), talc (0.6 mg) and ethyl cellulose (20mg) had the maximum
percentage of in vitro drug release (92.04%) in 8 hours along with satisfactory bioadhesive
strength (20.8 gm).

Mr. Thakur AtulKumar RanvirSing22 formulated mucoadhesive bilayered buccal tablets of

esomeprazole using polymers like HPMC K15M, sodium alginate, chitosan, polyvinyl
pyrollidone, carbopol 940,sodium CMC, Eudragit® and Ethyl cellulose. Unidirectional release
was achieved by preparing composite patches with backing membrane. The buccal patches
were tested for physical parameters like uniformity of weight, thickness, folding endurance,
swelling index, surface pH and in-vitro drug release studies. The results obtained were
within the prescribed limits. The physico-chemical compatibility of drug and polymers was
studied by FT-IR spectroscopy. The drug content was uniform in all the formulated buccal
patches of omeprazole. It was concluded that pantoprazole buccal patches provide
sustained delivery for prolonged periods in the management of gastro esophageal reflux.

Omeprazole
Omeprazole is the prototype member of substituted benzimidazoles which inhibit the final
common step in gastric acid secretion and have overtaken H2 blockers for acid-peptic
disorders. The only significant pharmacological action of omeprazole is dose dependent
suppression of gastric acid secretion; without anticholinergic or H2 blocking action. It is a
powerful inhibitor of gastric acid: can totally abolish HCl secretion, both resting as well as
that stimulated by food or any of the secretagogues, without much effect on pepsin,
intrinsic factor, juice volume and gastric motility. The oral absorption of omeprazole is
~50%, because of instability at acidic pH. Omeprazole 20 mg OD is effective for peptic ulcer.
Relief of pain is rapid and excellent. Faster healing has been demonstrated with 40 mg/day.
GERD can be treated with 20-60 mg daily in 1 or 2 doses.2
Amit E. Birari et al.,23 formulated mucoadhesive buccal tablets of omeprazole using
chitosan as primary polymer and carbopol 934, hydroxyl propyl methyl cellulose (HPMC
K4M) and Xanthan gum as a secondary polymer. The formulations were evaluated for
various parameters like hardness, friability, drug content, surface pH, swelling index, and
bioadhesive strength and in-vitro drug dissolution study. The surface pH indicates that
Chitosan alone is not suitable in designing mucoadhesive tablets and a combination of
Chitosan with other polymers produces tablets with neutral pH that are safe for mucosal
membrane. The swelling behavior of Carbopol is high in all the formulation wherever
Xanthan gum is used as more quantity and showed maximum release of Omeprazole from
the prepared tablets. The release studies indicated that the prepared Omeprazole
mucoadhesive tablets improved the bioavailabity by avoiding the first pass metabolism. The
in vitro studies have shown that this is a potential drug delivery system for Omeprazole with
a considerably good stability and release profile.

Koyi et al.,24 formulated bilayered buccal patches of omeprazole by solvent evaporation

method. Buccal patches were prepared by using hydrophilic polymers HPMC E15, Polyvinyl
alcohol and Eudragit in different ratios. The prepared patches were tested for physical
parameters like thickness, uniformity of weight, folding endurance, swelling index and
surface pH of patches and in-vitro drug release studies. The results obtained were within the
prescribed limits. The drug content was uniform in all the formulated buccal patches of
omeprazole. The results indicated uniform distribution of drug within the patches. The
release of omeprazole from the buccal patch was immediate up to 45 mins and sustained up
to 24hrs.Among the six formulations, the BM3 shows maximum drug release of 89.11% in
45 mins. IR spectroscopic studies indicated that the drug is compatible with the polymer.
The study clearly demonstrated that Omeprazole can be successfully delivered through
buccal route. The patches were non-irritating with favourable film properties and showed
sufficient mucoadhesive potential until the drug is absorbed from the formulation. So, it can
be concluded that buccal patches of HPMC meets the ideal pre requisites for a buccal device
which can be a good way to bypass hepatic first pass metabolism of omeprazole.

Khan et al.,25 formulated buccal films of omeprazole for paediatric drug delivery using
methyl cellulose (MC), hydroxypropylmethylcellulose (HPMC), sodium alginate (SA),
carragenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, and
L-arg as stabiliser. Omeprazole is an ideal candidate for buccal drug delivery, as it degrades
readily in acidic medium and undergoes first-pass metabolism. Ethanol was used as solvent
in addition to deionised water because drug and polymers are more soluble in ethanol than
water and the former also helped to increase the rate of drying. OME can only be stable in
alkaline solution with pH of eight and stability can be achieved either introducing cyclo-
dextrin or L-arg to the drug-loaded gel. However, because of the toxicity of cyclodextrin for
paediatric patients, use of L-arg was the preferred option. To determine the optimum
concentration of L-arg required to stabilise the drug and determine its effect on MET film
properties, different amounts relative to the drug were added to the original gels before
drying. Further, the distribution of OME and L-arg was more uniform in the films prepared
from the ethanolic gels (10 and 20% v/vEtOH). The most promising characteristics were
observed in plasticised MET films (0.50% PEG 400) prepared from ethanolic (20%v/v) gels
and containing OME: L-arg ratio of 1:2. These characteristics include transparency, ease of
peeling and flexibility of the films for further investigation. It was also confirmed that OME
originally loaded in crystalline form was molecularly dispersed (amorphous) within the MET
film matrix. The MET films have potential for paediatric buccal administration and will be
further functionally characterised to determine its in vitro cell culture, ex vivo and in vivo
performance.

Chul Soon Yong, Jae-Hee Jung, Jong-Dal Rhee, Chong-Kook Kim and Han-Gon Choi26
prepared buccal adhesive tablets of omeprazole with excellent bioadhesive force and good
drug stability in human saliva. The tablets were composed of sodium alginate,
hydroxypropylmethylcellulose (HPMC), alkali materials, and croscarmellose sodium. Due to
strong waterproofing effect, magnesium oxide only could be used as an alkali stabilizer for
omeprazole buccal adhesive tablets. Croscarmellose sodium enhanced the release of
omeprazole from the tablets. The physicochemical properties, such as bioadhesive force of
tablets and drug stability in human saliva, were investigated. The release kinetics and
bioavailability of omeprazole delivered by the buccal adhesive tablets were studied. The
tablet composed of omeprazole/sodium alginate/HPMC/magnesium oxide/croscarmellose
sodium (20/24/6/50/10 mg) could be attached on the human cheek without disintegration,
and it enhanced the stability of omeprazole in human saliva for at least 4 h and gave fast
release of omeprazole. The plasma concentration of omeprazole in hamsters increased to a
maximum of 370 ng/ml at 45 min after buccal administration and continuously maintained a
high level of 146–366 ng/ml until 6 h. The buccal bioavailability of omeprazole was found to
be 13.7% ± 3.2%. These results demonstrated that the omeprazole buccal adhesive tablet
would be useful for delivery of an omeprazole that degrades very rapidly in acidic aqueous
medium and undergoes hepatic first-pass metabolism after oral administration.

A. Figueiras et al.,27 studied the impact of cyclodextrins on the buccal permeation of

omeprazole. The effect of cyclodextrins to increase the in vitro transbuccal permeation of
Omeprazole was examined and the integrity, cytotoxicity and viability effects were
evaluated was studied using freshly obtained porcine buccal mucosa. The effect was
maximum with methyl-beta-cyclodextrin representing that this lipophilic cyclodextrin can
permeate buccal mucosa and consequently enhance drug delivery through the
biomembrane. The complexation of Omeprazole with methyl-beta-cyclodextrin in presence
of L-arginine increases drug permeation 2.4-fold, signifying that L-arginine favors drug
permeation due to the establishment of ionic interactions with negative charges present in
mucus layer on the surface of the mucosa. Stability studies performed at neutral conditions
suggested that the complexation of Omeprazole increased drug stability and this effect was
further improved in the presence of L-arginine. The viability studies of buccal mucosa
showed that it remains viable after 3 h incubation period with Omeprazole complexed with
cyclodextrins in absence and in presence of L-arginine. These results were validated by
histological evaluations. No toxicity effects were observed in buccal mucosa after incubation
with Omeprazole in complexed form even in the presence of L-arginine. The results
suggested that complexation of OME with methyl-beta-cyclodextrin in presence of L-
arginine was promising approach to increase drug stability and permeation through the
buccal mucosa, that ultimately can result in improve drug bioavailability.

Pantoprazole
Pantoprazole (dose, 10-40 mg) is newer H+ K+ ATPase inhibitor, similar in potency and
clinical efficacy to omeprazole, but is more acid stable and has higher oral bioavailability. It
is also available for i.v. administration; particularly employed in bleeding peptic ulcer and for
prophylaxis of acute stress ulcers. It used in treatment of erosion and ulceration of the
esophagus caused by gastro esophageal reflux disease. The oral bioavailability of
pantoprazole is 77% metabolised in the liver by cyp-450 system. Risk of drug interactions is
minimal.2

Thombre et al.,28 formulated mucoadhesive buccal tablet of pantoprazole. Poor

bioavailability of pantoprazole is associated with hepatic first pass metabolism. It was
observed that magnesium oxide stabilize the pantoprazole buccal adhesive tablet due to its
strong waterproofing effect, and prevent collapse. The adhesive tablet was composed of
pantoprazole-sodium alginate-HPMC K4M-magnesium oxide and reside in human saliva for
at least 6 h. Buccal adhesive tablet could be attached on human cheek depends on
combination of mucoadhesive polymer, Sodium alginate and HPMC K4M concentration.
Pantoprazole mucoadhesive tablet gave sustain release as well as fine mucosal diffusion.
Results suggested that pantoprazole would be an ideal candidate for buccal adhesive tablet,
as it degrades readily in acidic medium and undergoes first-pass metabolism following oral
administration. The in vitro release kinetics studies revealed that mucoadhesive tablet fits
well with zero order kinetics followed by Korsmeyer-Peppas, and Hixon Crow’s model and
the mechanism of drug release is non-Fickian diffusion.

Neelam sandeep reddy29 formulated buccal patches of pantoprazole by solvent casting

technique. The buccal patches were composed of different proportions and combinations of
HPMC and PVP. The polymer solutions were prepared separately and these polymer
solutions were poured into drug solution slowly drop by drop and both these solutions were
mixed. Propylene glycol was incorporated as a plasticizer at a concentration of 7% w/w of
total formulation. Buccal patches of pantoprazole showed satisfactory mucoadhesive
characteristics. The physicochemical evaluation indicated that the weight variation of the
formulated patches varied between 2.64 ± 0.06 (F1) and 2.94 ± 0.07 g (F3). Folding
endurance was measured manually. The highest folding endurance was observed in the case
of F3 (295) and the lowest in the case of F1 (210). It was concluded that pantoprazole buccal
patches provide sustained delivery for prolonged periods in the management of gastro
esophageal reflux.

Elsheikh Tajelsir, Aisha Khanum30 prepared mucoadhesive buccal patch of pantoprazole by

solvent casting method using 32 factorial design. The backing layer was prepared by
dissolving (5%) of ethyl cellulose in a mixture of acetone: isopropyl alcohol (60:40) with
glycerol (5%) as plasticizer. FB13 formulation showed satisfactory results of 226 ± 1.66, 280
± 2.77, 88.59 ± 2.31 for swelling index, mucoadhesive time, and invitro release respectively.
Release kinetics model was fitted in higuchi, with regression value of 0.998. Hence it has
been selected as optimized formulation and evaluated for further parameters such as
weight uniformity, thickness of patch, folding endurance, surface pH, drug content,
mucoadhesive strength. Ex-vivo permeation study on FB13 was carried out in buccal. The 3 2
factorial design design was used to study the effect of concentration changes of (Poly Vinyl
Alcohol) and (Xanthan Gum) on predetermined evaluation parameters. The %
concentrations of film forming agent PVA (x1) and mucoadhesive polymer XG (x2) were
selected as independent variables. The two factors were evaluated, each at three levels -1,
0, 1 indicating higher, middle, and lower levels of each factor. The actual; units for factor
(x1) were 0.5%, 1%, 1.5% and for factor (x2) were 1%, 1.5%, 2.0% respectively. The
dependent or response variables were swelling ratio (y1), mucoadhesive time (y2), and
cumulative release (y3). Buccal patch with ethyl cellulose backing membrane was prepared
to sustain the pantoprazole release, avoid the first pass metabolism, thus maintain the
therapeutic blood concentration for a prolonged period of time, and reduce the dose
frequencies and concentration can be achieved. The invitro release and permeation study
profiles showed a promising results with specified mucoadhesion period indicating that
Pantoprazole buccal patch would be a potential drug delivery system.

Malleswari K31 formulated pantoprazole buccal patches by solvent casting technique using
HPMC and PVP, in various combinations and proportions. Propylene glycol was incorporated
as a plasticizer at concentration of 7% w/w of total formulation. Buccal patches of
pantoprazole showed satisfactory mucoadhesive characteristics. The physicochemical
evaluation indicated that the weight variation of the formulated patches varied between
2.44 ± 0.06 (F1) and 2.94 ± 0.07 g (F5). It was concluded that pantoprazole buccal patches
provide buccal delivery for prolonged periods in the management of gastro esophageal
reflux, which can be a good way to bypass the extensive hepatic first-pass metabolism.

Sravani et al.,32 developed mucoadhesive buccal patches of pantoprazole by solvent

evaporation method using ethyl cellulose, HPMCK15M, eudragit, sodium carboxy methyl
cellulose, carboxy methyl cellulose, ethanol, poly ethylene glycol. Compatibility of drug and
excipients was studied by FTIR. The degree of swelling of formulations F1 to F5 was found to
be 7-26%. Formulation F1 with eudragit as a mucoadhesive polymer having more swelling
property that is about 26% compared with other polymer. Thickness of patch was in the
range of 0.05-0.12mm. F1 is having less thick. The surface Ph was measured which is
showing pH in the range of 6-7. The % mucoadhesion was found in the range of 66-85%.
Formulation F5 with ethyl cellulose was having more mucoadhesive property with 85%. F1
has maximum drug release about 85.7% up to 12 hrs. And F4 also maximum drug release up
to 76.97%., it is minimum for F3, F5 with a drug release of 70% up to 12hrs. The drug release
kinetics of F1 formulation show controlled release rate characteristic of drug. Thus the
formulation F1 was selected as a optimized formulation when compared to other
formulations.

Mittal et al.,33 formulated buccal mucoadhesive bilayered tablets of pantoprazole sodium

by direct compression method using HPMC K4M CR, Carbopol 974P, sodium alginate and
ethyl cellulose. The tablets were evaluated for physicochemical parameters like tablet
thickness, hardness, weight variation, assay. Thickness of tablets was measured by vernier
callipers. Hardness was measured by Monsanto tester and friability was determined in a
Roche friabilator. Pantoprazole Sodium mucoadhesive tablets were beneficial in reducing
multiple dosing, providing unidirectional release and avoiding extensive hepatic first pass
metabolism encountered during systemic therapy. The main advantage of developed buccal
tablets is that it contains lower drug dose that is sufficient for therapeutic effect. Thus the
formulation can be used for better bioavailability and improved patient compliance. HPMC
and sodium alginate were found to be ideal candidates among various bioadhesive
polymers. Polysorbate 80 was found to be valuable as a penetration enhancer while ethyl
cellulose formed an excellent backing membrane.
P N Vishnu Teja Naidu et al.,34 formulated buccal patches of pantoprazole by solvent casting
technique using different proportions and combinations of HPMC, PVP and propylene glycol.
The polymer solutions were prepared separately and these polymer solutions were poured
into drug solution slowly drop by drop and both these solutions were mixed. Propylene
glycol was incorporated as a plasticizer at a concentration of 7% w/w of total formulation.
The physicochemical evaluation indicated that the weight variation of the formulated
patches varied between 2.64 ± 0.06 (F1) and 2.94 ± 0.07 g (F3). It was concluded that
pantoprazole buccal patches provide sustained delivery for prolonged periods in the
management of gastro esophageal reflux.

Rabeprazole
Rabeprazole (dose, 10-40mg) is proton pump inhibitor used in treatment of erosion and
ulceration of the esophagus caused by gastro esophageal reflux disease. Its oral
bioavailability is 52% metabolized in the liver by cyp-450 system. The drug covalently binds
to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell
and suppresses the final step in gastric acid production. The binding to the (H+, K+)-ATPase
results in a duration of antisecretory effect.2

Nikhil A. Bhandiwadand35 designed buccal patch of rabeprazole sodium using HPMC E-15,
Sodium deoxycholate, PEG 6000 by solvent casting method. The study assessed the
suitability and feasibility of mucoadhesive buccal patch of Rabeprazole sodium with a goal
of protecting the drug from acidic degradation and increasing the permeability of
Rabeprazole sodium and thereby enhancing its bioavailability and the onset of action. The IR
spectra of the drug-polymer mixture revealed that there was no interaction between
polymer and drug, hence they were compatible. The DSC of the pure drug and buccal patch
indicated that the drug was successfully dissolved in the polymer matrix and encapsulated.
Polymer concentration was optimised in the range of 2%-5% w/v and permeation enhancer
concentration was optimised in the range of 1%-3% w/v. 32level factorial design was
adopted as study design at 3 levels of independent variables. The prepared patches were
characterised with respect to thickness, weight and folding endurance. The pH of the
patches were in the range of 7.34-7.59. The drug content of all the formulations was in the
acceptable range of 9.41 mg to 10.2 mg. Swelling index increased with increase in polymer
concentration. Moisture absorption was the least for the patches with highest polymer
concentration. In vitro drug release studies showed that the drug release from the patches
were dependent on the polymer concentration, i.e. with the increase in polymer
concentration, the rate of drug release decreased. Kinetic modelling revealed that the
patches followed a fickian type drug release mechanism.

Ann Rose Augusthy36 formulated mucoadhesive buccal patches of Rabeprazole using

gelatin, HPMC, PVP and propylene glycol by solvent casting technique and studied the
effects of permeation enhancers. Buccal Patches showed satisfactory physicomechanical
and mucoadhesive characteristics. The evaluation indicated all polymer combinations used
for fabrication of buccal patches showed film forming properties and reproducibility. The
examination suggested that fabricated films were thin, elastic, flexible, yellow colored
smooth and semi translucent; the thickness of these formulated buccal patches varied
between 0.7± 0.034 (F 14) and 0.38 ± 0.07 mm (F 3). The weight variation of these patches
varied between 89± 0.83 and 56 ± 0.67 mg. It was concluded that rabeprazole buccal
patches provide buccal delivery for prolonged periods in the management of gastro
esophageal reflux.

Rajput N et al.,37 formulated bilayered buccal tablets of Rabeprazole by direct compression

method using olibanum gum, carbopol 934 (CP) and xanthan gum. Various batches were
prepared by varying the ratio of different polymers either alone or in combinations with
varying ratios to identify the most effective formulation. The average weight of tablet was
found to be between 196.0 mm to 202.0 mm and maximum % deviation was found to be
±1.2 from all formulations. The thickness of all the tablets was found to be between 3.6 mm
to 3.8 mm and % deviation in thickness was found to be 0.02 to 0.18. Percent drug content
was found to be between 102.7% and 97.5%. The formulation F13 containing CP & OG 1:1 in
combination with Sodium deoxycholate showed suitable release kinetics and properties for
adhesion to the buccal mucosa and was free of any interaction between polymers and drug.

Sudeesh Edavalath et al.,38 formulated mucoadhesive buccal tablets of rabiprazole sodium

using different mixture of cellulose and polyacrylic derivatives to treat zollinger-ellison
syndrome. Twelve different formulations of buccal tablets were prepared, which contain
polymers such as Carbopol 934 P, Hydroxyl propyl methyl cellulose K4M (HPMC K4M),
Hydroxyl ethyl cellulose (HEC), Sodium carboxyl methyl cellulose (Sod CMC), and Hydroxyl
propyl cellulose (HPC) in various combinations. Tablets were prepared by direct
compression method and characterized by swelling studies, surface pH, % matrix erosion,
bioadhesive strength, in vitro drug dissolution and in vitro diffusion studies. All the
formulations gave the satisfactory result in terms of bioadhesive performance, physical and
mechanical properties and surface pH. Drug release and drug diffusion from the tablets
were depended on the ratio and type of the polymer used in the formulation. The best
mucoadhesive performance and best in vitro drug release profile were achieved by using
drug: Hydroxyl ethyl cellulose (HEC): Carbopol 934 P in a ratio of 1: 6: 1.5. The chosen tablet
containing 20 mg of Rabiprazole sodium performed 12 h sustained drug release with desired
therapeutic concentration.

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