oral drug delivery is convenient, non-invasive, and has a high patient compliance rate, it continues to be the most popular and preferred method of medicine administration. The majority of therapy treatments begin with this approach because it is not only the most economical butalso the easiest to use[ 1,2].It lowers the frequency of dosage and increases patient adherence[3]. Lipowski, a trailblazing formulation chemist, first presented this idea in the late 1930s[4]. His research paved the way for the development of contemporary sustained-release technologies, which are today essential to oral medication delivery. The limitations of traditional drug delivery techniques, which frequently lead to variable drug levels and related side effects, are intended to be addressed by sustained-release systems[5]. An illustration of this cutting-edge strategy are bilayer pills, which can deliver two distinct medications with separate release profiles. With an emphasis on boosting patient compliance, managing release patterns, and increasing medication bioavailability, oral drug delivery systems have undergone substantial development[5,6].It lowers the frequency of dosage and increases patient adherence. Lipowski,

a trailblazing formulation chemist, first presented this idea in the late 1930s[7].His research paved the way for the development of contemporary sustained-release technologies, which are today essential to oral medication delivery. The limitations of traditional drug delivery techniques, which frequently lead to variable drug levels and related side effects, are intended to be addressed by sustained-release systems[8] Tablets are the solid unit dosage forms which containing one or more active pharmaceutical ingredients and additives obtained by compression of uniform volume of particles[9]. The tablets are in the shapes by their formulation spherical, oval, oblong, triangle. The particles present in the tablets which consist of one or more active pharmaceutical ingredient with or without excipients such as diluents, lubricants, glidants, disintegrating agents, gastro intestinal behaviour modifying agents, flavouring and colouring agents. The various tablets are swallow tablets, chewing able Tablet, Mucoadhesive tablets, dispersed or dissolving tablets, sublingual tablets.

Tablets are the unit dosage formulation which offers highest capabilities..Dose precision and very less content variability[10].Packaging and strips are very economical and minimum time required. Suitable for large scale production. Identification is easy..Easy to administration and self-administration is possible. Gastric ulcers are a break in the mucosa of the stomach lining that penetrates through the muscular is mucosa and extends more than 5 mm in diameter. When alterations occur to the defense mechanisms of the stomach, it can cause changes in the gastric mucosa which will eventually result in erosion and then ulceration. This activity reviews the evaluation and management of gastric ulcers and explains the role of the inter professional team in improving care for patients with this condition. Gastric ulcers are a common clinical presentation in the United States and often lead to the expenditure of millions of healthcare dollars. They are a break in the mucosal barrier of the stomach lining that penetrates through the muscularis mucosa and are greater than 5 mm in diameter[9,10]. The body has natural ways to protect the stomach mucosa from the harmful acidic environment that is the gastric lumen. When alterations occur to these defenses, it can lead to changes in the gastric mucosa which will eventually cause erosion and then ulceration. Gastric mucosa protection is via prostaglandins, mucous, growth factors, and adequate blood flow. Known damaging factors of this barrier include smoking, hydrochloric acid, ischemia, NSAID medications, hypoxia, alcohol, and Helicobacter pylori infection. Gastric ulcers are a part of peptic ulcer disease, which carries a lifetime prevalence of 5 to 10% of patients, which is likely an underestimation of the disease as some patients may remain asymptomatic. Studies have shown that the prevalence of gastric ulcers increases with age and with the chronicity of NSAID use[11]. Research shows that smoking leads to a relative risk of times that of non smokers for developing gastric ulcers. There is no difference between men and women in the prevalence of gastric ulcers. The prevalence of Helicobacter pylori infection at age 60 approximates 50% in the US population. Estimates are that 25% of chronic   NSAID  users will develop gastric ulcers. The pathophysiology of gastric ulcer development depends on the insult. Since about 80 to 90% of gastric ulcers result from either Helicobacter pylori and/or NSAID[12]. First, regarding Helicobacter pylori these bacteria colonize about 45-50% of the stomach mucosa worldwide. It is a bacterium that people are inoculated with at an early age, especially in developing countries with lower socioeconomic status and crowded households. These bacteria induce an inflammatory response in the host that leads to an epithelial response, degeneration, and injury, known as gastritis[13]. Typically, patients with this infection develop pan gastritis. This damages the antral somatostatin release, which leads to an increase in gastrin secretion, which stimulates increased acid production. Patients who develop gastric ulcers are those in whom the bacteria have remained in the antrum. Parietal cells of the more proximal gastric body still have full production capabilities preventing ulcer genesis in this area. Of note, not all patients with this infection are symptomatic; this depends on the virulence of the bacteria and other host risk factors[14]. A common bacterial virulence factor is the production of cag A, which leads to more cytokine cell destruction and mucosal damage. Antibiotics that disrupt DNA synthesis in anaerobic organisms (H. pylori): The 5 nitroimidazoles, metronidazole and tinidazole, were found to bind to the same subset of proteins, including thioredoxin reductase. E. histolytica and T. vaginalis , none of the other bound proteins in G. lamblia are likely candidates for involvement in the thioredoxin mediated redox network. Notably, translation elongation factor EF 1?, essential for protein synthesis, was extensively degraded following treatment with 5 nitroimidazoles. All tested nitroimidazoles reduced intracellular thiol pools in G. lamblia , but metronidazole had the least effect, differing significantly from its impact on the other two parasites. This indicates that nitroimidazole drugs affect G. lamblia in a fundamentally different manner than they do E. histolytica and T. vaginalis . The selective toxicity of 5 nitroimidazoles to microaerophiles and anaerobes is thought to be due to the presence of factors in these organisms that can transfer electrons to the nitro group, thereby activating the prodrug metronidazole to its active form. Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It      is suggested that the toxic free radicals covalently bind to DNA,causing DNA damage and leading to cell death. The mechanism by which  tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar. For the treatment of the trichomoniasis caused by T. vaginalis in both female and male patients. Also for the treatment of giardiasis caused by G. duodenalis in both adults and pediatric patients older than three years of age and for the treatment of intestinal amebiasis and amebic liver abscess caused by the E. histolytica in both adults and pediatric patients older than three years of age. Omeprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The main part of its metabolism depends on the polymorphically expressed CYP2C19, which is responsible for the formation of hydroxyomeprazole, the major metabolite found in plasma. The remaining part depends on CYP3A4, responsible for the formation of the omeprazole

sulphone. Omeprazole, according to the FDA label is a proton pump inhibitor (PPI) used for the following purposes: Treatment of active duodenal ulcer in adults. Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults. Treatment of active benign gastric  ulcer in adults . Reduction of risk of upper gastrointestinal (GI) bleeding in critically ill adult  patients. Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year  of age and older. Treatment of erosive esophagitis (EE) due to acid mediated GERD in patients  1 month of age and older. Maintenance of healing of  due to acid mediated GERD in patients  1 year of age and older. pathologic hypersecretory conditions in adults

MATERIALS AND METHODS

Omeprazole and Tinidazole purchased from Sigma Aldrich, Micro crystalline cellulose and starch purchased from Nice chemicals,Magnesium stearate,Sodium starch glycolate,Quinolin yellow, Talc  purchased from LOBA chemie

PREFORMULATION STUDIES[15]

As a starting point to developing dosage forms, various physical and chemical properties of the drug substance need to be documented. These investigations are termed preformulation studies. In the rational development of dosage form Preformulation studies are the important and initial step. The aim of preformulation study is to develop information about the drug substances, so that this information would be useful to develop a formulation. It is an essential study for physical and chemical properties of a drug substances alone and in combination with excipients. Preformulation investigation is designed to identify the physiochemical properties of drugs and excipients that may influence the formulation design, method of formulation pharmacokinetic and biopharmaceutical properties of the resulting product. These studies are performed for the preformulation investigation.

Melting point:

The powdered drug is placed into a capillary tube, which is then sealed at one end. The capillary tube should be 6 7 cm in length and 1 mm in diameter, with the drug standing 3 4 mm from the bottom. The tube is moistened with a liquid from the bath and positioned in an iron stand attached to a thermometer. Adjust the setup so that the drug in the capillary is aligned with the middle of the thermometer’s mercury bulb. The thermometer is then lowered into a beaker filled with paraffin oil. The beaker is heated slowly while maintaining a uniform temperature with constant stirring. Once the drug in the capillary starts to show signs of melting, removethe burner while continuing to stir. Record the temperature at which the drug fully melts and becomes transparent.

 Preparation of Buffer Solutions:

1. Phosphate Buffer (pH 7.4):

Dissolve 8.40 grams of sodium dihydrogen phosphate (NaH?PO?) and 15.62 grams of disodium hydrogen phosphate (Na?HPO?) in 1000 ml of water. Stir until fully dissolved.

2. Acidic Buffer (0.1N HCl):

Pipette 8.34 ml of concentrated hydrochloric acid (HCl) into a 1 liter volumetric flask.

Dilute with distilled water up to 1000 ml and Mix thoroughly to ensure even distribution.

Formulation Trials:

To develop an optimized bilayer tablet formulation, several trials were conducted.

The general procedures for each layer in all formulation trials are outlined below.\

Formulation Procedure for Layer 1:

Dispensing:

Dispense the materials required for the first layer into separate poly bags to keep them organized and ready for the next steps.

Sifting:

Pass the materials through selected sieves to achieve a uniform particle size and ensure better mixing.

Formulation Procedure for Layer I:

1. Dry Mixing:

In a mortar, mix the API with microcrystalline cellulose, lactose monohydrate, and sodium starch glycolate for approximately 10 minutes until thoroughly blended.

2. Binder Solution:

Prepare the binder solution by mixing starch with a sufficient amount of purified water to enhance the mechanical strength of the formulation layer.

3. Granulation:

Add the prepared binder solution to the dry mixed materials. Mix thoroughly to ensure uniform distribution and pass the mixture through a #60 sieve.

4. Drying:

Load the granulated blend into a rapid dryer and dry it at an internal temperature of 50°C with an airflow rate of 50 until the loss on drying falls within the range of 1.5% to 2.5%.

5. Lubrication:

Add talc and magnesium stearate to the dried blend to improve its flow properties.

Formulation Procedure for Layer II:

Dispensing:

Dispense the materials required for the second layer into separate poly bags and prepare them for the next steps.

Sifting:

Pass the materials through a series of specified mesh sizes to achieve uniform particle size and ensure effective mixing.

Formulation Procedure for Layer II:

1. Dispensing:

Dispense the materials required for the second layer into separate poly bags and prepare them for processing.

2. Sifting:

Sift the materials through a series of specified mesh sizes to ensure uniform particle size and effective mixing.

3. Binder Solution:

Prepare the binder solution by mixing starch with an adequate amount of purified water to enhance the mechanical strength of the formulation.

4. Dry Mixing:

Mix the API II with microcrystalline cellulose and Tartrazine yellow in a mortar for approximately 10 minutes until thoroughly combined.

5. Granulation:

Add the prepared binder solution to the dry mixed materials and mix thoroughly. Pass the mixture through a #60 mesh sieve.

6. Drying:

Load the granulated blend into a rapid dryer and dry at an internal temperature of 50°C with an airflow rate of 50 until the loss on drying falls within the range of 1.5% to 2.5%.

7. Sifting:

Sift the dried blend through a #20 mesh size. Retain the granules and mill them, then pass the blend through a #20 mesh again before pre lubrication.

8. Pre Lubrication:

Sift guar gum polymer and set it aside. Add it to the blend and mix for 20 minutes.

9. Lubrication:

Add talc and magnesium stearate to the pre lubricated blend to improve its flow properties.

Pre compression parameters: (M.Sunitha reddy et al.,2018) The formulated blends have undergone following preformulation studies,

• Bulk density
• Angle of repose
• Carr’s compressibility studies
• FT-IR studies
• Hausner’s ratio

Bulk density (Db):

The bulk density depends on the particle size distribution, cohesiveness and shape of the particles. 10gm powder is accurately weighted and poured in to a graduated measuring cylinder through a funnel and shaken without tapping, the volume which is measured is called initial bulk. Bulk density is expressed in gm/cc is given by,

Bulk density (D b)  =     ???????????????? ???????? ???????????? ????????????????????(????????)

???????????????? ???????????????????????? ???????? ????????????????????????(????????)

Tapped density (Dt):

10gm of powder is taken for the determination of bulk density is dropped from the particular height in to a measuring cylinder. The cylinder is tapped constantly until there is no change in the volume of the powder and tapped volume was read. The tapped volume is expressed in gm/cc is given by,

Tapped density (D t) =            ???????????????? ???????? ???????????? ????????????????????????(????????)

???????????????????????? ???????????????????????? ???????? ????????????????????????(????????)

 Angle of repose (?):

 The fractional force in a loose powder can be determined by the angle of repose. This is the maximum angle possible between the surface of pile of powder and the horizontal plane. The powder is allowed to fall through the fixed funnel in a definite height. Angle of repose is calculated by measuring the height and radius of the heap of powder produced

? = tan -1 ( h / r )

Carr’s index(CI)

The percentage compressibility of powder is direct measurement of the potential powder arch or the bridge strength and stability. Carr’s index of each formulation was calculated by the equation given below,

CI=   ???????? ? ????????

????       × ????????????

Where, Df = tapped density, 

D0 = bulk density

Hausner’s ratio(IH):

Is calculated from the df and do using the following expression

Hausner’s ratio (IH) = ???????????????????????? ????????????????????????????

???????????????? ????????????????????????????