RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

|1. |NAME OF THE CANDIDATE AND ADDRESS: |Permanent address |

| | |ARCHANA. R |

| | |D/O RAJANNA N |

| | |#10, Manjunatha flour mills , |

| | |chandapura ,anekal(tk) |

| | |Bangalore-562106, |

| | |Karnataka |

| | |Postal address |

| | |Krupanidhi college of Pharmacy, |

| | |#12/1, Chikka Bellandure, Carmelaram Post, |

| | |Varthur Hobli, |

| | |Bangalore-560035 |

| | |Karnataka |

|2. |NAME OF THE INSTITUTE: |Krupanidhi College of Pharmacy, |

| | |#12/1, Chikka Bellandur, Carmelaram Post, |

| | |Varthur Hobli, |

| | |Bangalore – 560035, |

| | |Karnataka |

|3. |COURSE OF THE STUDY & SUBJECT: |MASTER OF PHARMACY (PHARMACEUTICS) |

|4. |DATE OF ADMISSION TO THE COURSE: | July 2011 |

|6. |BRIEF RESUME OF THE INTENDED WORK: |

| | |

| |6.1 Need of Study: |

| |Oral drug delivery has been known for decades as the most widely utilized route of administration among all the routes that have been explored |

| |for the systemic delivery of different dosage forms. Proton-pump inhibitors (PPIs) have been very efficacious for the management of a variety of |

| |acid-related disorders such as dyspepsia, peptic ulcer, gastroesophageal reflux disease, laryngopharngeal reflux, Barrett’s esophagus, |

| |gastrinomas, Zollinger -Ellison syndrome. |

| |Proton pump inhibitors act by irreversibly blocking the H+/K+ adenosine triphosphatase enzyme system, more commonly known as gastric proton |

| |pump) of the gastric parietal cells. These drugs are absorbed into systemic circulation, diffuse into parietal cells of stomach and accumulate in|

| |the acid secretory canaliculi. Here proton activation takes place and tends to bind covalently with sulfhydryl groups of cysteine in H+/K+ |

| |ATPase, irreversibly inactivating the pump molecule. This provides a suppression of 24 to 48 hours as this is final step in gastric acid |

| |secretion1. |

| | |

| |Gastro resistant tablets(enteric coated) are used to resist the drug release in the gastric mucosa. These tablets remain intact in the stomach |

| |but quickly release in the upper intestine. The tablets are coated with polymers like cellulose acetate phthalate, polyvinyl acetate phthalate, |

| |hydroxypropylmethylcelluose phthalate. These polymers are esters, insoluble in gastric medium up to PH 4 and are intended to hydrate and begin |

| |dissolving as the tablet leaves the stomach, enter the duodenum(pH 5 to 6) and move furthur to small intestine where pH is 7to8 to release the |

| |drug. The primary mechanism by which these polymers lose their integrity, there by admitting intestinal fluid and releasing drug is ionization of|

| |the residual carboxylic groups on the chain and subsequent hydration. |

| | |

| |ADVANTAGES OF ENTERIC COATING DRUG DELIVERY SYSTEM |

| |To prevent irritation when directly exposed to gastric mucosa. e g aspirin |

| |To prevent degradation of acid labile drugs. |

| |Delivery of active pharmaceutical agents into intestine. |

| |To provide a delayed release component for repeat action tablet. |

| |To prevent nausea and vomitting when drugs are released in the stomach. |

| |To prevent the degradation of drugs at lower pH in the stomach. |

| |e g erythromycin2. |

| | |

| |Objective of Study: |

| |The aim of this work is development and evaluation of gastro |

| |resisitent tablet of proton pump inhibitor. |

| |In order to fulfill this aim we shall: |

| |Select the appropriate drug for the solid oral dosage form. |

| |Select excipients including polymers to develop the dosage form based on physico-chemical properties and compatibility of the Active |

| |Pharmaceutical Ingredient (API) and excipients. |

| |Preformulation studies on the API and excipients for the proposed formulations. |

| |Formulation of gastro resistant proton pump inhibitor tablets. |

| |In vitro evaluation of the formulations as per official & in-house protocols. |

| |Optimization of the dosage form based on evaluated parameters. |

| |Stability Study of the optimized formulation as per ICH guidelines. |

| | |

| |Review of Literature |

| |Anroop B Nair et al., studied the formulation and evaluation of enteric coated tablet of proton pump inhibitor for esomeprazole trihydrate with |

| |different polymers like Eudragit L-30 D-55, HPMC Phthalate, celluloseacetate Phthalate. The tablet showed good integrity, desirable for enteric |

| |coated tablets. Dissolution studies showed better dissolution for Methacrylic polymer than cellulose polymers3. |

| | |

| |A Mukharya et al., studied the Stable and Bioequivalent Formulation Development of Highly Acid Labile Proton Pump Inhibitor. The main challenge|

| |in the formulation of Rabeprazole tablets was the degradation of Rabeprazole upon exposure to acidic environment. Thus, to prevent exposure of |

| |Rabeprazole in gastric acidic environment enteric coating was done and to prevent interaction between Rabeprazole and acidic enteric coating |

| |material, seal coating was done over the core tablet. They have reported that the formulation did not release Rabeprazole in gastric acidic pH |

| |and released 91% of Rabeprazole in 45 minutes at intestinal alkaline pH4. |

| | |

| |Sindhu Abraham et al., studied the development and optimization of sublingual tablet of rabeprazole sodium, these were prepared by wet |

| |granulation process based on formulation variables including crospovidone and croscarmellose sodium. Optimization of tablet formulation showed |

| |short wetting time of 22 seconds and in vitro dispersion time 32 seconds6. |

| | |

| |UK medicines information pharmacists group studied the difference between the drugs like esomeprazole 40 mg, omeprazole 20 or 40 mg, |

| |pantoprazole 40 mg, lansoprazole 30 mg and rabeprazole 30 mg dosed once daily among 36 patients with gastro reflux disease symptoms. Studies |

| |showed that esomeprazole maintained intragastric pH levels at above 4 for longer periods than other drugs7. |

| | |

| |Hemanth Kumar Sharma et al., reported that Pantoprazole is a proton pump inhibitor prodrug used in the treatment of gastric ulcers and |

| |gastroesophageal disease. Pantoprazole must be absorbed in the gastrointestinal tract and because it is unstable under acidic conditions, enteric|

| |delivery systems are required. The purpose of this study was to prepare Pantoprazole loaded microbeads by ionotropic gelatin technique using |

| |sodium alginate and natural Mucoadhesive substance from the fruit of Dillenia indica followed by a coating with Eudragit L 100-55. The |

| |microspheres have been characterized in terms of their morphology, particle size, encapsulation efficiency, swelling ratio, mucoadhesivity and |

| |ability of stabilizing Pantoprazole in acidic media. Different formulation variables like polymer-polymer ratio, drug-polymer ratio and coating |

| |concentration were considered. Almost spherical microbeads were obtained with sufficient swelling, Mucoadhesive property and acid resistance. |

| |Dissolution study was followed at phosphate buffer (pH 7.4) for 8 hr8. |

| | |

| |Santhosh Kumar Jindal et al., formulated oral drug delivery device for insulin and to protect the sensitive drug from digestive enzymes and |

| |proteolytic degradation in stomach and upper part of gastro intestinal tract (GIT). So, for this purpose insulin enteric microspheres (EMS) were |

| |prepared using Hydroxy propyl methyl cellulose acetate succinate as enteric polymer, Bacitracin as protease inhibitor and Sodium oleate as |

| |absorption enhancer. In-vitro drug release studies determined that almost no drug was released in HCl (pH 1.2) for 2 hours and then maximum |

| |amount of drug was released within 70 minutes in Phosphate buffer (pH 7.4). In-vivo studies on male wistar rats confirmed a remarkable decrease |

| |in blood glucose level after 2 hours of administration of insulin EMS9. |

| | |

| |J Williams et al., In a randomised single blind crossover study in children with cystic fibrosis and pancreatic insufficiency, two enteric |

| |coated microsphere preparations of pancreatin were compared on a capsule for capsule basis, by measuring the coefficient of fat absorption, |

| |nitrogen excretion, weight change, and symptom scores after four weeks treatment with each preparation. Thirty nine subjects were randomly |

| |allocated to receive pancrease followed by Creon or vice versa. Each individual subject received the same number of capsules per day in each |

| |study period. Data from 27 children (Pancrease/Creon, n=13 and Creon/Pancrease, n=14) were suitable for analysis. Results showed no significant |

| |differences between the two preparations in any variable studied. We conclude that there is no significant difference between Pancrease and Creon|

| |when compared on a capsule for capsule basis10. |

| | |

| |S. Bozdag et al., prepared various coating solutions in different concentrations and applied to previously sub coated omeprazole tablets to |

| |examine whether this coating prevented omeprazole from degrading in acidic media.Dissolution tests were conducted in acidic and basic media to |

| |determine the appropriate coating ratio. For stability evaluation, an accelerated stability test was performed on developed tablet formulations |

| |and commercially obtained capsules. Samples were examined with regard to visual appearance, omeprazole content and dissolution properties for a |

| |month. For formulation consideration, the most promising results were obtained from HPMCP4 and CAP4 (4% enteric coating with hydroxypropyl methyl|

| |cellulose phthalate solution and cellulos acetate phthalate solution, respectively) sub coded preparations. From the stability aspect only Losec |

| |capsules (Astro-Turkey, commercial product) seem to be dependable11. |

| | |

| |Sumith Chakraborty et al., reported that Pantoprazole 5-(difluoromethoxy)- 2-[(3,4-dimethoxypyridin-2-yl) methylsulfinyl]- 3H-benzoimidazole is a|

| |proton pump inhibitor belongs to group of benzimidazole . This compound inhabits gastric acid formation and there by it is very efficient for the|

| |treatment of gastric and duodenum ulcers. In aqueous media more acidic than pH 4 it suffers a practically complete decomposition within a period |

| |shorter than 10 minutes. Even in solid state it is sensitive to heat, humidity, light and especially to substances containing an acidic group. |

| |Pantoprazole which have an irritant effect on the stomach, can be coated with a substance that will only dissolve in the small intestine. For |

| |such types of drugs, enteric coating added to the formulation tends to avoid the stomach's acidic exposure, delivering them instead to a basic pH|

| |environment (intestines pH 5.5 and above) where they do not degrade, and give their desired action. This stumulate us to formulate and evaluate |

| |pantoprazole as enteric coated tablet12. |

| | |

| |Rabia Bushra et al., reported that Ibuprofen is a propionic acid derivative that belongs to the class NSAIDs. Major adverse reactions associated |

| |with Ibuprofen are related to GIT and include peptic and mucosal ulcers, dyspepsia, severe gastric pain and bleeding, that results in excessive |

| |treatment failure. The goal of the study was to develop enteric coated Ibuprofen tablets in order to avoid gastric mucosal irritation, diffusion |

| |of drug across mucosal lining and to let active ingredient be absorbed easily in small intestine. The formulation was developed and manufactured |

| |through the direct compression process, the simplest, easiest and most economical method of manufacturing. Enteric coating was done using an |

| |Opadry white sub coating and an aqueous coating dispersion of Acryl-Eze. Enteric coated formulation was subjected to disintegration and |

| |dissolution tests by placing in 0.1 M hydrochloric acid for 2 h and then 1 h in phosphate buffer with a pH of 6.8. About 0.04% of drug was |

| |released in the acidic phase and 99.05% in the basic medium. These results reflect that ibuprofen can be successfully enteric coated in order to |

| |prevent its release in the stomach and facilitate rapid release of the drug in the duodenum, due to the presence of superdisintegrant. |

| |Formulating this enteric coated tablet could increase patient compliance by decreasing adverse drug reactions (ADRS) associated with Ibuprofen |

| |therapy13. |

| | |

| |A.R.Pohlmann., studied the gastro resistant microparticles containing sodium pantoprazole, stability studies and in vivo antiulcer activity. |

| |This loaded microparticles are prepared by spray drying in pilot scale using eudragit s 100 as polymer. Studies showed that microparticles had |

| |acceptable stability under accelerated condition and were efficient in protecting the stomach against ulceration caused by ethanol14. |

|7. |Materials & Methods: |

| |7.1 Source of Data: |

| |Preliminary data required for the experimental study would be obtained |

| |From Pubmed, Science Direct & other internet facilities. |

| |Literature search & related articles from library of Krupanidhi College of pharmacy |

| |Preformulation & formulation development work will be performed in the pharmaceutics PG laboratory, Krupanidhi College of pharmacy, Bangalore. |

| | |

| |7.2 Method of Collection of Data (including sampling procedure, if any): |

| |The physiochemical properties of the drug will be collected from drug information centre. Various standard books journals websites and other |

| |sources like research literature databases like medline, sciencedirect, pubmed are followed. |

| |The experimental data will be collected from the study of drug and literature. Its formulation was done through investigation of process and |

| |product variables are evaluated in laboratory of Krupanidhi college of pharmacy Bangalore. |

| | |

| |Data on drugs will be collected from drug information center, standard books physicochemical database and literature search. Extensive |

| |preformulation trial provides the basis of selecting the excipients and system for final formulation development and finally the system was |

| |evaluated |

| | |

| | |

| |Method:Dry Granulation process, Wet Granulation and Direct Compression |

| |method. |

| |7.3. Evaluation Studies |

| |Precompression parameters |

| |Bulk density |

| |Tapped density |

| |Loss on drying |

| |Particle size distribution |

| |Angle of repose |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| |Post compression parameters |

| |Hardness test |

| |Weight variation |

| |Content uniformity |

| |Disintegration test |

| |Dissolution test |

| |Friability |

| |Thickness |

| |Sampling procedure: |

| |Official tests Pharmacopoeial procedure will be followed. For in house methods of evaluation standard validasted procedures supported by |

| |published data shall be adopted |

| | |

| |7.3 Method of Screening: |

| |z7.3 Does the study require any investigations or interventions to be conducted on patients or other human or animals? If so please describe |

| |briefly: |

| | |

| |-NO- |

| |7.4 Has the Ethical Clearance been obtained from your Institution in case of 7.3? |

| | |

| |-NOT APPLICABLE- |

| | |

|8. |LIST OF REFERENCES: |

| | |

| |1.Willeminjtje A, Moogerwerj and Pankaj jay pasricha. Goodman and Gillman’s. The pharmacological basics of therapeutics. 11th ed. 2006. |

| | |

| |2. Herbert A, Libermann, Joseph L, Kanio. Leon Lachmann. The theory and practice of industrial pharmacy. 3rd ed. Indian: Varghese:1990.P.331-2. |

| | |

| |3. Anroop B Nair, Rachna Gupta, Rachna Kumaria Shery Jacob and Mahesh Attimmarad. 2010 “Formulation and Evaluation of enteric coated tablets of |

| |proton pump inhibitor”. Jbclinpharm, 1(4)215-21. |

| | |

| |4. A.Mukharya, S.A.chaudhary, A.Bheda, A.Mulay, N.Mansuri et al., Stable and bioequivalent formulation development of highly acid labile proton |

| |pump inhibitors: Rabeprazole. Int.J of pharm res 2011:(2):1-8. |

| | |

| |5. Dr.Udupa N, Sreedhar D, Kumar D, Pise A, Janodia MD. Proton Pump Inhibitors- An-Overview. Latest Reviews. 2006;4(3). |

| | |

| |6.Sindhu Abraham et al.studied Development and Optimization of sublingual tablet of Rabeprazole Sodium.Int. J pharm res 2010;(5):50-53. |

| | |

| |7. UK Medicines information pharmacists group 2001: |

| | |

| | |

| |8. Hemanth kumar Sharma, Siba Prasad Pradhan, Babita Sarangi. 2010 “Preparation and in-vitro evaluation of enteric controlled release |

| |pantaprazole loaded microbeads using natural mucoadhesive substance from Dillenia indica L”. Int. J. PharmTech Res, 2(1):542-51. |

| | |

| |9. Santhosh Kumar Jindhal, Malkeet Singh, Mansh Goswami. 2009 “Formulation and Evaluation of insulin enteric microspheres for oral drug |

| |delivery”. Acta Pharma Sci, 51:121-7. |

| | |

| |10. J Williams, A MacDonald, P H Weller, J Fields, H Pandov et al, 1990 “ Two enteric coated microspheres in cystic fibrosis”. Arch Dis |

| |Child,65:594-7. |

| | |

| |11. S. Bozdag, S.Calis and M. Sumnu. 1999 “Formulation and stability evaluation of enteric –coated omeprazole formulations”. S.T.P. Pharma |

| |science,9(4) :321-7 |

| | |

| |12. Sumit Chakraborty, Sibaji Sarkar and Sujit Kumar Debnath. 2009 “Formulation |

| |Development and Evaluation of Pantoprazole Enteric coated Tablets”. Int.J. Chem |

| |Tech Res,1(3)633-66. |

| | |

| |13. Rabia Bushra, Muhammad Harries Shoaib, Nousheen Aslam, Zafar Alam Mehmood Durriya Hashmat. 2010 “Enteric coating of ibuprofen tablets (200mg)|

| |using an aqueous dispertion system”.Brazilian jornal of Pharmaceutical Sciences, 46(1):99-107. |

| | |

| |14. A.R.Pohlmann, R.P.Raffin, L.M.Colome, E.E.S.Schapoval, D.S.Jornada, Gastro resistant micro particles containing sodium pantoprazole: |

| |stability studies and invivo Anti-ulcer activity 2007(1):28-35. |

|9. |Signature of the Candidate | |

| | | |

| | | |

| | | |

| | |(ARCHANA.R) ((Rajesh |

|10. |Remarks of the Guide: This is an industrial project aimed at developing a marketable product comparable to excellent brand product available. |

| |The project shall impart sufficient expertise in the researcher in every step of formulation development, evaluation and scale up. Recommended |

| |for approval. ANTIOXIDANAND ANTIMICROBIAL ACTIV |

|11. |Name & Designation (in BLOCK LETTERS) |

| | |

| |11.1 Guide |Prof. Dr. R.S. THAKUR |

| | |Professor and Head |

| | |Department of Pharmaceutics |

| | |Krupanidhi College of Pharmacy, |

| | |Bangalore-35. |

| |11.2 Signature of Guide | |

| | | |

| | |(Mrs. ROHINI R. M.) |

| |11.3 Co-Guide | |

| | | |

| |11.4 Signature of Co-Guide | |

| | | |

| |11.5 Head of the Department |Prof. Dr.R.S THAKUR |

| | |PROFESSOR AND HEAD |

| | |Department of PharmaceuticaTechnology |

| | |Krupanidhi College of Pharmacy |

| | |Bangalore – 560035. |

| |11.6 Signature of HOD: | |

| | | |

| | | |

|12. |12.1 Remark of the Principal: |

| | |

| | |

| | |

| |12.2 Signature of the Principal |Prof. Dr. N. PREM KUKAR |

| | |PRINCIPAL |

| | |Krupanidhi college of pharmacy, |

| | |ChikkaBellandur, Carmelaram Post, |

| | |Varthur Hobli, |

| | |Bangalore – 560035 |

| | |Karnataka |

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5. TITLE OF THE TOPIC:

“DEVELOPMENT AND EVALUATION OF GASTRO

RESISTANT TABLET OF PROTON PUMP INHIBITOR”

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