OMEPRAZOLE pH SENSITIVE MICROSPHERES PREPARATION AND EVALUATION

Introduction Microspheres Most of our microspheres are polystyrene-based, although some other base polymers are also offered. Plain (non-functionalized) polymer microspheres are ideal for protein adsorption applications, while surface modified microspheres (COOH or NH2) are used for covalent ligand attachment. Cross-linked polymer microspheres are available for improved solvent, heat, and pressure resistance. Polymer microsphere Coating Microspheres Polymer microspheres present a flexible platform for applications in diagnostics and bioseparations. They may be coated withrecognition molecules such as antibodies, antigens, peptides, or nucleic acid probes, and can be loaded with hydrophobic dyes and other compounds. Unmodified polymer spheres also find extensive use as standards for instrument set-up and calibration. A. Protein Adsorption Polystyrene microspheres are ideal for protein adsorption and have been utilized in a range of diagnostic tests and assays. Reference our TechNote 204, Adsorption to Microspheres, for protein adsorption guidelines, information on the use of blockers, and further references. B. Covalent Ligand Attachment Surface modified microspheres are available with carboxyl or primary amine groups for covalent ligand attachment. Reference our TechNote 205, Covalent Coupling, which provides a basic foundation for successful attachment of a variety of ligands through coupling protocols, buffer recipes, blockers, and references.

C. Affinity Binding Affinity binding systems offer simple and efficient ligand attachment. Coatings of Fc-binding proteins are able to orient antibodies for optimal activity, and streptavidin offers extremely stable attachment of biotinylated molecules such as proteins, peptides, and oligonucleotides. See TechNote 101, ProActive Microspheres, for basic attachment protocols. NEED FOR THE STUDY The floating drug delivery system or hydrodynamicaly balanced system are among the several approaches that have been made developed in order to increase the gastric transit time of drug. The microspheres are characteristically free flowing powders consisting of natural or synthetic polymers and ideally having a particle size less than 200m. Microspheres incorporating a drug dispersed or dissolved throughout particle matrix have the potential for the controlled release of drug1 Microspheres are one of the multiparticulate delivery system and are prepared to obtain controlled the drug release from the dosage form to improve bioavailability, reduces the adverse action and prolong the action of drug, reduce absorption difference in patients, reduce the dosing frequency and adverse effects during prolong treatment. It is needed to formulate in long acting dosage form, reaching to effective biological site rapid.2,3 Omeprazole is usually administered as conventional tablet form with the dose 20 mg, Omeprazole is proton pump inhibititor which prevent stomach from producing gastric acid. The biological half life of Omeprazole is 1-2 hr. Microspheres are one of the multiple unit dosage forms. Solvent evaporation method is the preparation technique that is widely preferred for the preparation of controlled release microspheres. To prepare emulsion by adding the dispersed phase consisting of drug, polymer and appropriate dispersion agent in organic solvent to dispersion medium which is immiscible with the dispersed phase

and minimatrix forms are obtained by removing the solvent used at the dispersed phase from the droplets which are formed in the emulsion6.

Advantages of microspheres: 1. Taste and odor masking of drug 2. Protection of drug against the environment (moisture, light, heat and oxidation) 3. To improve the bioavailability 4. To decrease the side effects 5. To reduce the dose frequency 6. To relative stability 7. To increase the patient compliance 8. To have better therapeutic efficacy 9. To reduce the fluctuation in plasma drug concentration 10. Safe handling of toxic substances

Among the micro particulate systems, microspheres have a special importance since it is possible to target drug and provide controlled release.8 In this present study is aimed to prepare Floating microspheres containing Omeprazole to achieve a controlled drug release profile as well as to increase the gastric transit time.

Omeprazole
/w EPDw UJNzEw

Omeprazole is a an oral antiulcer agent. Omeprazole is characterized as a gastric acid pump inhibitor because it blocks the final step of gastric acid production. It has a long duration of action and is very potent, allowing for once-daily administration. Despite its potency, it must be used in combination with antibiotics to be effective against Helicobacter pylori. Due to concern regarding long-term use, it was originally approved by the FDA in September 1989 for acute treatment only. In December 1994, an FDA advisory committee recommended it be approved for maintenance therapy of healed erosive esophagitis. In April 1996, it was approved for the treatment of H. pylori-associated duodenal ulcer. Belongs to a new class of antisecretory agents, the substituted benzimidazoles, which suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of parietal cells. it, following activation in an acidic pH, binds irreversibly to the H+/K+ ATPase pump on the secretory surface of the parietal cell membrane. Subsequently, the secretion of hydrogen ions into the gastric lumen is inhibited. it inhibits both basal and stimulus-induced acid secretion.

Litrature survey Review of Literature: An explicit literature review was done by exploring through various national & international journals, official standard reference books and by surfing through various websites on the internet. Varaporn et.at. studied the floating property and release characteristic of hallow microsphere of Acyclovir.the microspheres were prepared by solvent evaporation technique. The present study shows that the hallow microspheres improve the bioavailability and patients compliance by prolonging the residence time in gastrointestinal track. E.Dini et.at, synthesis and characterization of cross linked chitosan microspheres containing an hydrophilic drug, Hydroquinone. The microspheres were prepared by suspension cross linking method using glutaraldehyde. It was found that slower drug release rate was obtained from microspheres prepared by using a high concentration of chitosan Anandkumar Shrivastava et.at. preparation of characterization of floating microsphere of cemitidine. The cemitidine microsphere were prepared by solvent evaporation method,thus this study shows that floating microspheres will increase the gastric residence time T. Comoglue et.at. in this work prepared the microspheres of pantaprazole by solvent evaporation method and characterize.the pantaprazole is the proton pump inhibitor. Use in treatment of gastric ulcer and gastroesophagal disease. so purpose of this study was to developed the microspheres that absorb through gastrointestinal track

 Hui Yun Zhou et.at. prepared the Cellulose acetate (CA) /Chitosan multimicrospheres of Ranitidine. He microsphere prepared by w/o/w emulsion technique. The concentration of CA and the ratio of CA:chitosan influence the drug release. It prolong the release of Ranitidine [1] K Takeuchi, K Akira, Journal of Gastroenterology and Hepatology.,1999, 142, 251. [2] JD Korwin, P Ducrotte, T Vallot, Presse Med., 2004, 33, 11, 746. [3] J Bateman, B Teusher, R Telford, Pharmaceutics I (PSCI), 2002, 423. [4] A Farinha, A Bica, Eur J Pharm Sci., 1999, 7, 4, 311. [5] S Bozdang, S Calis, M Sumnu, Farm Vestn., 1997, 48, 119. [6] A Pilbrant, C Cederberg, Scand J Gastroenterol., 1995, 20, 336. [7] C Cederberg, T Anderson, I Skanberg, Scand J Enterol., 1989, 166, 33. [8] ML Buck, Pediatric Pharmacotherapy., 1999, 5: 4A. [9] VP Pandey, A Phanindrudu, Boll Chim Farm., 2002, 141, 6, 419. [10]M Turkoglu, H Varol, M Celikok, Eur J Pharm Biopharm., 2004, 57, 2, 279. [11]MA Navarro, N Raei, Gastroenterol Hepatol., 1998, 21, 2, 63. [12] AR Kulkarni, KS Soppimath, TM Aminabhavi, J Controlled Release., 2001, 75, 331. [13] RC. Ganorkar, F Liu, M Baudys, SW Kim, J Controlled Release., 1999, 59, 287. [14] AR Kulkarni, KS Soppimath, WE Rudzinski, TM Aminbhavi, Drug Met Rev., 2000, 33, 149. METHOD SELECTED OBJECT:- To prepare pH sensitive microspheres ABSTRACT Omeprazole, a proton-pump inhibitor used in peptic ulcers, gastroesophageal-reflux disorder,

Zollinger-Ellison syndrome and in H. pylori infections. The omeprazole is unstable at acidic pH, undergoes degradation in stomach. To prevent the degradation in stomach, dosage forms are supplied as enteric-coated tablets or granules encapsulated in gelatin capsules. The efficiency of such dosage forms depends upon the - extent of coating, solubility of coating material; type of dosage form etc. Recently, pH-sensitive polymer are utilized to deliver drug to intestine. The polymer swells only in alkaline pH and releases the drug as it enters the intestine. In this research, pH-sensitive formulations were developed to deliver the omeprazole effectively. Using the stimuli-responsive polyacrylamide-g-sodium alginate polymer, microspheres were prepared by coaservation followed by cross-linking with gluteraldehyde. Omeprazole drug were loaded in microspheres. All microspheres were evaluated for size distribution, content uniformity, in vitro dissolution and pulsatile swelling study. Pharmacological screenings were done for antacid and antiulcer activities of different omeprazole containing formulations. Results indicated that the pH, free acidity, total acidity, and ulcer-index in both non-lighted and ligated ulcer models were comparatively reduced in rats treated with the omeprazole containing pH-sensitive microspheres than enteric-coated granules than neat omeprazole. Thus, developed formulation release was superior in intestine and thus produced superior action. INTRODUCTION Omeprazole, a proton-pump inhibitor is widely prescribed for the treatment of peptic ulcer,

Zollinger-Ellison syndrome, Gastro-esophageal reflux disease (GERD), H.Pylori infection and NSAID associated ulcers. Its oral bioavailability (40-50%) in humans is poor due to acid sensitivity and first pass metabolism. Attempts were made earlier to improve the bioavailability by formulating it as enteric-coated granules encapsulated in gelatin shell and enteric-coated tablets. The efficiency of such dosage forms depends upon the number of parameters such as extent of coating, solubility of coating material and type of dosage form etc. In the present study, omeprazole was encapsulated in acrylamide and that was crosslinked with gluteraldehyde. These microspheres are sensitive to pH changes and release the drug in an alkaline pH undergoing swelling. Microspheres were prepared by coaservation followed by crosslinking with gluteraldehyde. They were then evaluated for content uniformity, size analysis, in-vitro dissolution and pulsatile swelling. Absence of interaction between omeprazole and polymer was determined using IR spectral data. Pharmacological screening was carried out for antacid and antiulcer activities using pylorus ligation and non-ligation methods in rats. The parameters used to evaluate where change in pH, total acidity and ulcer index. The results were compared against data generated for neat omeprazole, and two marketed formulation viz. OMEZ, OCID. DRUG PROFILE- omeprazole

 Chemical formula:-C17H19N3O3S Molecular weight:- 345.416 Categories:

Anti-Ulcer Agents Enzyme Inhibitors Proton-pump Inhibitors

Mechanism of action:Omeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity. DRUG INTRACTION:Interaction Omeprazole may increase the effect of the Alprazolam benzodiazepine, alprazolam. This gastric pH modifier decreases the levels/effects Atazanavir of atazanavir Chlordiazepoxide Omeprazole may increase the effect of the Drug

Cilostazol Clonazepam Clorazepate Cyclosporine Diazepam Estazolam Flurazepam Fosphenytoin Indinavir Itraconazole Ketoconazole Midazolam Methotrexate Halazepam Ketazolam Prazepam Quazepam

benzodiazepine, chlordiazepoxide. Omeprazole increases the effect of cilostazol Omeprazole may increase the effect of the benzodiazepine, clonazepam. Omeprazole may increase the effect of the benzodiazepine, clorazepate. Omeprazole increases the effect and toxicity of cyclosporine Omeprazole may increase the effect of the benzodiazepine, diazepam. Omeprazole may increase the effect of the benzodiazepine, estazolam. Omeprazole may increase the effect of the benzodiazepine, flurazepam. Omeprazole increases the effect of hydantoin Omeprazole decreases the absorption of indinavir The proton pump inhibitor, omeprazole, may decrease the absorption of itraconazole. The proton pump inhibitor, omeprazole, may decrease the absorption of ketoconazole. Omeprazole may increase the effect of the benzodiazepine, midazolam. Omeprazole increases the levels of methotrexate Omeprazole may increase the effect of the benzodiazepine, halazepam. Omeprazole may increase the effect of the benzodiazepine, ketazolam. Omeprazole may increase the effect of the benzodiazepine, prazepam. Omeprazole may increase the effect of the benzodiazepine, quazepam.

Triazolam Mephenytoin Phenytoin Ethotoin Voriconazole St. John's Wort Dasatinib Enoxacin Disopyramide

Tacrolimus

Tipranavir

Trimipramine

Cefditoren

Omeprazole may increase the effect of the benzodiazepine, triazolam. Omeprazole increases the effect of hydantoin Omeprazole increases the effect of hydantoin Omeprazole increases the effect of hydantoin Voriconazole increases the effect and toxicity of omeprazole St. John's Wort decreases the levels/effects of omeprazole Omeprazole may decrease the serum level of dasatinib. Omeprazole may decrease the absorption of enoxacin. The beta-blocker increases toxicity of disopyramide Omeprazole may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Omeprazole therapy is initiated, discontinued or altered. Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Omeprazole. Consider alternate therapy or increase the dose of Omeprazole based on the therapeutic response. The strong CYP2C19 inhibitor, Omeprazole, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Omeprazole is initiated, discontinued or dose changed. Proton pump inhibitors such as omeprazole may decrease the serum concentration of cefditoren. If

Clopidogrel

possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Omeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Clopidogrel prescribing information recommends avoiding concurrent use with omeprazole, due to the possibility that combined use may result in decreased clopidogrel effectiveness

CLINICAL PHARMACOLOGY:Pharmacodynamics: Omeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Omeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase at the secretory surface of the gastric parietal cell. As a result, it inhibits acid secretion into the gastric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Mechanism of action: The inhibitory effect of omeprazole on gastric acid secretion in vivo and in vitro is presented. In the gastric fistula dog omeprazole was found to be about 10 times more potent than cimetidine. When

omeprazole was administered in vivo, the inhibition of acid secretory rates was found to correlate with the degree of inhibition of the gastric H+K+ATPase purified from the omeprazole treated animals. The inhibitory action of omeprazole was found to depend on acid induced transformation of omeprazole into an active inhibitor of the gastric H+K+ATPase, as no inhibition was obtained when omeprazole was incubated under neutral conditions with either the isolated gastric mucosal or the H+K+ATPase preparations. A model is proposed in which the inhibition of acid formation is mediated by an inhibitory compound generated from omeprazole within the acid compartment of the parietal cell.

Side effect:Diarrhea; gas; headache; nausea; stomach pain; vomiting.Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); bone pain; chest pain; dark urine; fast, slow, or irregular heartbeat; fever, chills, or sore throat; red, swollen, blistered, or peeling skin; severe diarrhea; severe stomach pain or cramps; swelling of the hands, ankles, or feet; unusual bruising or bleeding; unusual tiredness; vision changes; yellowing of the eyes or skin. Storage:- Store below 25C Uses:Omeprazole is used to treat a number of problems. It is a member of a class of drugs called proton pump inhibitors, sometimes known as PPIs.

In general, this drug is used to treat gastro-oesophageal reflux disease (GORD), or gastric or duodenal (upper intestinal) ulcers. Benefits of being on this drug include the prevention of excess acid production by the stomach which can lead to the relief of GORD symptoms and may allow healing of ulcers or erosions. Listed below are the typical uses of omeprazole:

Treatment of gastro-oesophageal reflux disease (sometimes called GORD, dyspepsia or heartburn) and relief of associated symptoms such as dyspepsia (indigestion, including pain, bloating or nausea), heartburn and epigastric pain (pain in the chest behind the breast bone) Treatment of duodenal (upper intestinal) and gastric (stomach) ulcers and erosions, including ulcers associated with non-steroidal anti-inflammatory (NSAID) drug use Eradication of a bacteria (Helicobacter pylori) which is often found in the gut and is the cause of stomach ulcers in many patients (omeprazole is used in combination with antibiotics for this purpose). Prevention of stomach acid aspiration (inhalation of stomach acid into the airways), which may happen during a surgical operation Controlling symptoms of ZollingerEllison syndrome (a disorder in which excess stomach acid is produced). a high dose given intravenously following surgical treatment of severe peptic (stomach) ulcer bleeding treatment may prevent a recurrent of ulcer bleeding.

Warnings:- Omeprazole should be used with caution in: those with liver disease. It should not be used in: patients with dyspepsia (indigestion) or a suspected stomach ulcer if there are 'alarm' symptoms of stomach cancer (bleeding in stools, difficulty in swallowing, recurrent vomiting or weight loss) as this means there is a possibility of cancer which needs to

be excluded before treatment with omeprazole is started, as omeprazole treatment may temporarily relieve some cancer symptoms and so delay cancer diagnosis. Half Life:- 0.5-1 hour Absorption:- Absorption is rapid, absolute bioavailability (compared to intravenous administration) is about 30-40% at doses of 20-40 mg Exepient Data: Acrylamide Structure

Chemical formula:- C17H14N4O Molecular weight:- Average: 290.3193

 Sodium alginate Structure

Chemical formula:- (C6H7NaO6)n Molecular weight:- 222 (actual average) Solubility:- Dissolves slowly in water, forming a viscous solution; insoluble in ethanol and ether Used as:- Stabilizer, thickener, gelling agent, emulsifier Material and Method:Materials:1) Drug: Omeprazole 2) Polymers: HPMC,PEG6000,Acryl amide, Sodium Alginate,Poloxomer etc Method:Preparation of microspheres by solvent evaporation method Development of formulation and evaluation

Grafted polymer synthesis Sodium alginate (Na-alg) was hydrated for 24 hr with constant stirring. Acrylamide (AAm) solution was then added followed by (0.005mol) of ceric ammonium nitrate (CAN). The mixture hours. The grafted polymer was precipitated by acetone and washed with methanol. It was then dried overnight under Production of pH-sensitive microspheres The grafted polymer solution was added drop wise into a solution of gluteraldehyde in a mixture of ethanol and HCl to obtain microspheres. These were then stirred for 1 h, decanted and washed with water. They were made pH-sensitive by stirring in 1 M NaOH for 4 Drug was loaded into the microspheres by stirring them in drug solution for 4 h, decanting them,

Preformulation studies:HPLC analysis method Omeprazole samples were analyzed using a modified reversedphase high performance liquid chromatography (HPLC) method [9] employing a water instrument with a Shimadzu UV detector set at 302 nm and a water US-60 injector. The samples were eluted at a flow rate of 1.0 mL/min at room temperature, under isocratic conditions. Separation was achieved using octadecylsilane column -Bondapak C18 column (Waters Assoc.; 10 m, 150 mm 3.9 mm id). The mobile phase consisted of acetonitrile: phosphate buffer pH 7.5 (25:75% v/v). Standard calibration curves, based on the average of the peak height of different concentrations using a known amount of drug in

the concentration range of 0.5-5.0 g/mL, were used to determine the intra- and inter-day precision of the method. Standard solutions were prepared daily by dissolving the appropriate amount of drug in ethanol to yield the final solution (10 g/mL), and the calibration curves were constructed before each sample set was analyzed to ensure reproducibility of the analysis. Kinetic study Degradation of omeprazole in aqueous solutions (effect of pH) The effect of pH (6.0, 7.5, 9 and 10) of the medium on the stability of omeprazole was carried out at constant temperature of 25C. Solutions of omeprazole were prepared in the selected buffer at different pH values. The solutions were placed in brown glass vials covered with Teflon lined screw caps and stored at 25C in a thermostatically controlled oven (Heraeus thermostatic oven, Karl Kolb Scientific technical supplies, Buchschlag-Frankfurt, Germany). At different time intervals, 0, 24, 48, 72, 96, 120, 168 h, samples were taken out of the oven, frozen immediately and kept in a freezer (- 20C) until they were analyzed. EVALUATION PARAMETERS FOR pH SENSITIVE MICROSPHERES

The evaluation of microspheres shall be carried out by using following instruments. o Compatibility study: - Compatibility of drug with various polymers will be investigated using UV/IR. o Surface Morphology: SEM/ Optical microscope. o Particle size determination: Sieve analysis/SEM/Optical microscope.

o Estimation of drug content by using UV-Spectroscopic method o In vitro dissolution study: USP Dissolution Apparatus (DISSO 2000, LAB INDIA)

EVALUATION Identification of omeprazole was by comparison with that of an authentic sample and by verification of the presence of functional groups in its infra-red (IR) spectra. Also, various concentrations of the drug in 0.1M HCl were evaluated by ultraviolet (UV) spectroscopy (Shimadzu 1700) to determine if it would obey Beers law.

Particle size determination

The particle size of the microspheres was determined with an optical microscope under regular polarised light, and mean particle size was calculated by measuring 100 microspheres (n = 3) with the help of a calibrated oculometer. Tapped density Tapping method was used to calculate tapped density. The volume of a weighed quantity of the microspheres was determined, after 100 taps, using a tapped density apparatus (Pharma Chem Machineries, model CBD 100), DT = MT/VT ... (1) where DT = tapped density, MT is mass of microspheres and VT = volume of microspheres after tapping Carrs (Compressibility) index This parameter was calculated from bulk density (the ratio of weighed quantity of microspheres to its volume), DP, and tapped density as in Eq 2 [9] Compressibility index = (DT DP)/DTx100 ... (2)

Angle of repose The angle of repose, q, of the microspheres, which measures resistance to particle flow, was determined by the fixed funnel method [10] and calculated as in Eq 3. Tan q = S/D .... (3) where S = surface area of the free standing height of the microspheres heap and D = diameter of the heap. Scanning electron microscopy Scanning electron microscopy (SEM) studies were performed to determine the porous/hollow nature of the microspheres. Surface morphology of microspheres was also noted. Drug loading The drug content of the floating microspheres was carried out by dissolving the microspheres in a small amount of dichloromethane in a separating funnel and extracting the drugs into 0.1N HCl by evaporating the dichloromethane. Determination of drug loading (n = 3) was carried out at 288 nm spectrophoto-metrically In vitro floatability In vitro floatability studies on floating microspheres were carried out using USP XXIV dissolution apparatus II [11]. The microspheres were placed in 0.1M hydrochloric acid containing 0.02 %v/v Tween 80 with the paddle rotating at 100 rpm for 12 h. Tween 80 served to mimic the effect of natural surfactants in the stomach. The floating and the settled portions of the microspheres were recovered separately, dried and weighed. Buoyancy (floatability) was calculated as in Eq 4. Buoyancy (%) = Qf / (Qf + Qs) x 100 .. (4) where Qf and Qs are the weights of the floating and the settled microspheres, respectively.

In vitro drug release studies Drug release studies were carried out in a six-basket USP XXIV dissolution apparatus type I rotating at 100 rpm in 0.1M hydrochloric acid as dissolution medium (900ml) maintained at 37 0.5 C. At specific time intervals, up to 12 h, aliquots were withdrawn and analysed at 288 nm spectrophotometrically (Shimadzu 1700) after suitable dilution. The withdrawn volume was replaced with an equal volume of fresh 0.1M hydrochloric acid to maintain sink conditions. All experiments were performed in triplicate. The drug release data were fitted to Zero order (cumulative % drug release versus time), First order (log cumulative % drug retained versus time) and Higuchi models (cumulative % drug released versus square root of time) to assess the kinetics of drug release and determine the release mechanism of the drug from the floating microspheres. RESULTS AND DISCUSSION Development of formulation and evaluation Grafted polymer synthesis and production of pH-sensitive microspheres The grafted polymer obtained with different ratio of Na-alg and AAm are shown in (Table 1). FTIR studies The FTIR spectra of omeprazole, Na-alg, Na-alg-g-pAAm, microspheres containing omeprazole are displayed in (Figures 1 - 4). The peak at 1616 cm-1 shows the CN imine group present in the microspheres by the crosslinking between the gluteraldehyde and CAN and polymers. The microspheres containing omeprazole shown peak at 1700 cm-1 indicated the presence of pendent gluteraldehyde in the microspheres. The spectra results that there is no interaction between omeprazole and polymer. And it shows the presence of all peaks, which were present in the cross-linked polymer and pure omeprazole.

Swelling studies The % water uptake Q was 108 at acidic pH and 1552 at alkaline pH and shown in (Table 2). This indicates that pH sensitive microspheres were highly swellable at alkaline medium, hence facilitates the drug release in intestine. The swelling was displayed in (fig 5). Drug release studies In-vitro drug release studies were carried out in simulated gastric solution for 12 h and the release of drug in acidic pH was very low where as it increases in intestinal pH and shown in (fig 6). The release data were fitted with Peppas equation, and the values of k, n, t calculated and is displayed in (Table 3). The calculated values of n were found to be 0.4 to 0.6 and the values of k ranges from -1 to 5 min 10 -2 . Antiulcer studies Antiulcer and anatacid properties were estimated for neat omeprazole, OMEZ,OCID and microspheres containing omeprazole. The pyloric ligation and nonligation methods results were tabulated in (Table 4 - 7) for 30 min and 4 h after the drug pyloric ligation and non-ligation respectively. The ulcer protection of pH-sensitive microspheres was superior to neat omeprazole and marketed formulation.

FTIR SPECTRUM of OMEPRAZOLE

FTIR spectrum of SODIUM ALGINATE

% grafting, drug content, and microspheres size S.No 1. 2. 3.

Polymer (Na-alg-g-pAAm) % of Grafting Drug content microspheres size (in m)

55-45 45-55 35-65

25 35 45

18.3 20.8 23.7

780.5