FORMULATION AND IN-VITRO EVALUATION OF

CAPTOPRIL FLOATING MATRIX TABLETS

M.PHARM DISSERTATION PROTOCOL

Submitted to

Rajiv Gandhi University of Health Sciences,

Bangalore, Karnataka.

By

Mr. Sandeep Jagannath Sonawane B. Pharm.

Under the Guidance of

Prof. Basawaraj S. Patil

M. Pharm. (Ph. D).

DEPARTMENT OF PHARMACEUTICS R.M.E.S’s COLLEGE OF PHARMACY,

GULBARGA-5851022010-2011

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.

CURRICULUM DEVELOPMENT CELL

CONFORMATION FOR REGISTRATION OF SUBJECT

FOR DISSERTATIONRegistration No. :

Name of the Candidate : Mr. Sandeep Jagannath Sonawane

Name of the Institution : R.M.E.S’s College of Pharmacy

Gulbarga, Karnataka.

Course of Study and Subject : M. Pharm. in Pharmaceutics

Date of Admission to the Course : 30th June 2010

Title of the Topic : Formulation and in-vitro evaluation of

Captopril floating matrix tablets.

Brief resume of the intended work : Enclosed

Signature of the student :

Guide Name : Prof. Basawaraj S. Patil. M.Pharm.(Ph.D)

Remarks of the Guide : Recommended for approval

Signature of the Guide :

Co-Guide Name : Mr. Upendra Kulkarni. M.Pharm. (Ph.D)

Signature of the Co-Guide :

HOD Name : Prof. Hariprasanna R.C. M.Pharm. (Ph.D)

Signature of the HOD :

Director/Principal Name : Prof. Kishoresingh K. C. M.Pharm. Ph.D

Mobile : +919880200905

Director/Principal E-mail ID : rmepharmacy@gmail.com

Remarks of Director/Principal : Recommended for approval

Director/Principal Signature :

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name and Address of the candidate

MR. SANDEEP JAGANNATH SONAWANEA/P- Dhamori Kd;Tal- Rahuri, Dist- Ahmednagar, MS.Pin- 413704

2. Name of the Institution R.M.E.S’s College of Pharmacy, Gulbarga, Karnataka- 585102

3. Course of study and subject Master of Pharmacy in Pharmaceutics

4. Date of admission to course 30th June 2010

5. Title of the topic Formulation and in-vitro evaluation of Captopril floating matrix tablets.

6. Brief resume of the intended work

6.1 Need of the study

Floating drug delivery systems were first described by Davis in 1968. 1,2 It is possible to prolong the gastric residence time of drugs using these systems. Several techniques are used to design gastro retentive dosage forms. These include, floating drug delivery systems (FDDS), high-density DDS, mucoadhesive systems, swelling and expanding DDS, modified shape systems, and other delayed gastric devices.3-5 Floating drug delivery systems, also called as hydrodynamically balanced system, is an effective technology to prolong the gastric residence time in order to improve the bioavailability of the drug.6 This technology is suitable for drugs with an absorption window in the stomach or in the upper part of small intestine,7 drugs acting locally in the stomach8 and for the drugs that are poorly soluble or unstable in the intestinal fluid.9 Floating drug delivery systems have a bulk density lower than the gastric fluid and thus remain buoyant in the stomach, without affecting gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly.4 Based on the mechanism of buoyancy, two distinctly different technologies, that is non effervescent and effervescent systems, have been utilized in the development of floating drug delivery systems. The effervescent floating drug delivery systems utilize matrices prepared with swellable polymers and effervescent components eg: sodium bicarbonate and citric acid or stearic acid. The matrices are fabricated such that in the stomach carbon dioxide is liberated by the acidity of the gastric contents and is entrapped in the gellified hydrocolloid. This produces an upward motion of dosage form and maintains its buoyancy. In non-effervescent floating drug delivery systems, the drug is mixed with gel forming hydrocolloid, which swells on contact with the gastric fluid after oral administration and maintains relative integrity of shape and bulk density of less than unity within and outer gelatinous barrier. The air trapped by the swollen polymer confers buoyancy to these dosage forms.4,10

Captopril, an antihypertensive agent, has been widely used for the treatment of hypertension and congestive heart failure. Captopril is rapidly absorbed and has bioavailability of about 75% and half life is approximately 2 hours.11 It has been

reported, however, that the duration of antihypertensive action after a single oral dose of Captopril is only 6-8 hours, so clinical use requires a daily dose of 37.5-75 mg to be taken three times .12 It is most stable at pH 1.2 and as pH increases, it becomes unstable and undergoes a degradation reaction.13 The virtue of the prolonged release dosage form of Captopril has been reviewed.14 The objective of this present investigation is to formulate floating matrix tablets of Captopril by using different polymers to prolong the gastric residence time and increase the drug bioavailability.

6.2 Review of Literature:

1) Basak SC, et al.(2004).15 Formulated oral floating matrix tablets of Ciprofloxacin using gas generating agent sodium bicarbonate and hydrophilic polymer hydroxy propyl methyl cellulose (HPMC). In vitro drug release study of tablets indicated controlled sustained release for Ciprofloxacin and 80-89% release at the end of 8 hours.

2) Ziyaur Rahman, et al. (2006).16 Prepared bilayer floating tablets (BFT) for captopril using different compression technology. HPMC, K-grade and effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained captopril and various polymers such as HPMC-K15M, PVP-K30 and Carbopol 934p, alone or in combination with the drug. The floating lag time was 10 min and the tablet remained floatable throughout all studies.

3) Patel VF, et al. (2007).17 Prepared Monolithic floating matrix tablets of Dipyridamole by using hydrophilic polymer, polyethylene oxide and ratio of lactose to starch 1500. All formulations had total floating time of more than 12 hours. As content of polymer increased the release rate declined with increase in value of diffusion exponent giving anamolous drug release to zero order drug release (p<0.05). Lactose gave higher drug release with release mechanism towards zero order compare to starch 1500 which gave slower release with release mechanism towards diffusion based.

4) Jaimini M, et al. (2007).18 Prepared Famotidine floating tablets employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.

5) Patel DM, et al. (2007).19 Prepared Carbamazepine floating tablets using melt granulation technique. Bees wax was used as hydrophobic meltable material. Hydroxy

propyl methyl cellulose, sodium bicarbonate and ethyl cellulose were used as matrixing agent, gas generating agent and floating enhancer, respectively. The tablets were evaluated for in vitro buoyancy and dissolution studies. Formulation S3 was selected as a promising formulation and was fond stable at 400 and 75% relative humidity for three months.

6) Thakkar VT, et al. (2008).20 Prepared Levofloxacin hemihydrate floating tablets by direct compression method using Gelucire 43/01 (hydrophobic) and hydroxypropylmethylcellulose (hydrophilic) polymer in different ratios. In vitro release study reveals that increasing the proportion of Gelucire 43/01, 5 to 40%, decreased the release rate of drug. The release rate of levofloxacin hemihydrates from matrices was mainly controlled by the hydrophilic and hydrophobic polymer ratio. Matrix tablet containing 25% HPMC K4M and 15% Gelucire 43/01 (F4 batch) showed a release as target profile. Optimal batch (F4) was selected by regression analysis which followed Higuchi kinetic.

7) Shweta Sharma, et al. (2009).21 Prepared Captopril floating matrix tablets with various grades of HPMC in varying ratios to formulate the floating tablets. Lactose was used as a diluent in the preparation of the tablets. Sodium bicarbonate was incorporated into the tablets to aid buoyancy of the tablets. it was concluded that the formulation F1 is the best formulations as the extent of drug release was found to be around 85 %.

8) Prajapati ST, et al. (2009).22 Floating matrix tablet of Domperidone were prepared by wet granulation technique, using polymers such as hydroxy propyl methyl cellulose K4M, carbopol 934P, and sodium alginate, either one or in combination, and other standard excipients. In vitro release mechanism was evaluated by linear regression analysis. Floating matrix tablets based on combination of three polymers namely; hydroxyl propyl methyl cellulose K4M, carbopol 934P and sodium alginate exhibited desired floating and prolonged drug release for 24 hours. Carbopol loading showed negative effect on floating properties but were found helpful to control the release rate of drug.

9) Havaldar VD, et al. (2009).23 Prepared floating matrix tablets of Atenolol by direct compression method. All the formulations, except F2, F3 and F6 showed Korsemeyer-Peppas model as the best fit model. Formulation F2 and F3 showed first order model while F6 showed zero order model. Diffusion exponent (n) value was found in the rage of 0.52-0.99 indicating diffusion as a release mechanism.

10) Danki Lingaraj S, et al. (2010).24 Prepared Hydrodynamically Balanced Systems (HBS) of Alfuzosin hydrochloride tablet using Hydroxy propyl methyl cellulose (HPMC) of different viscosity grades at three different drugs to polymer ratios, different diluents and gas generating agents by direct compression technique. The rate of drug release decreased with increased polymer concentration. It was found that HPMC viscosity had significant impact on the drug release from the prepared HBS.

11) Zawar Laxmikant R, et al. (2010).25 Prepared floating mucoadhesive tablets of Clarithromycin by direct compression using directly compressible polymers such as HPMC K4M, HPMC K15M and carbopol 974P and were evaluated for drug -

excipient compatibility, density, buoyancy test, mucoadhesion force, swelling study, drug content and in-vitro release profile. Sodium bicarbonate and citric acid were used for producing effervescent base for buoyancy of tablets. Analysis of drug release from tablet indicates drug release by zero order rate kinetics.

12) Akash Yadav, et al. (2010).26 Prepared gastro retentive floating microballoons of Metformin by the emulsion solvent diffusion technique using acrylic polymers (i.e. Eudragit RS-100 and Eudragit S-100) with drug (metformin) in a mixture of ethanol, dichloromethane and propanol. The drug encapsulation efficiency was high. Incorporation of Eudragit RS-100 and Eudragit S-100 in the microballoons proved to be an effective method to achieve the desired release behavior and buoyancy.

13) Ritesh Kumar, et al. (2010).27 Formulated sustained release floating matrix tablets of Metformin hydrochloride using gas generating agent (potassium bicarbonate) and hydrophilic gelling polymer hydroxyl propyl methyl cellulose (hypromellose) by wet granulation technique. The prepared formulations were evaluated for floating time and in vitro drug release characteristics using modified dissolution method. All formulations possessed good floating properties with total floating time more than 12 hours. Formulations with high amount of hypromellose were found to float for longer duration and provide more sustained release of drug. The formulated drug delivery system was found to be independent of pH. Release kinetics of formulations followed Higuchi model with anomalous non-fickian diffusion.

14) Sudhir Kumar Yadav, et al. (2010).28 Prepared floating tablets of Ranitidine hydrochloride by direct compression method using natural and synthetic polymers. The drug release kinetic was fitted in three different mathematical models like- Zero order, Higuchi and Korsmeyer-Peppas model. The results indicate that the drug release mechanism was found fickian diffusion type in most of the formulations.

15) Anilkumar Shinde J, et al. (2010).29 Sustained release of floating tablets of Cephalexin were formulated employing the hydrophilic polymer hydroxy propyl methyl cellulose (HPMC), gas generating agent sodium bicarbonate and citric acid. The tablets containing CFL released 72.28 to 99.461 % of drug at the end of 12 hrs by in vitro release study. The drug release from the tablets was sufficiently sustained followed the Korsmeyer and Peppas model controlled mechanism of cephalexin tablet.

16) Gupta SK, et al. (2010).30 Prepared floating tablets of Acyclovir containing polyvinyl pyrrolidon (PVP), polyvinyl alcohol (PVA) and hydroxy propyl methyl cellulose (HPMC) as the polymers and sodium bicarbonate as a gas generating agent, to reduce floating lag time and tablets were prepared by wet granulation method. On the basis of evaluation parameter formulation AV4 selected as developed formulation.

17) Lakshmi Narasaiah V, et al. (2010).31 Formulated Sumatriptan Succinate floating tablets by wet granulation method using hydroxy propyl methyl cellulose (HPMC) as gel forming agent and sodium bicarbonate and citric acid were incorporated as gas generating agents. The drug release for all the formulations were followed by zero order kinetics and Peppas modeling. The diffusion exponent of formulations was found (n<0.89) to be nonfickian (Anomalous) diffusion mechanism.

6.3 Objectives of the study

The present research investigation is planed with the following objectives.

1) To formulate floating matrix tablets of Captopril using different polymers.

2) To evaluate the formulations with respect to various physical parameters.

3) To evaluate the formulations with respect to content uniformity, floating capacity,

water uptake study, in-vitro dissolution study etc.

4) The release data will fit into different kinetic models.

5) To characterize the formulation by instrumental methods like FTIR and DSC.

6) To perform the stability studies on promised formulation.

7. Materials and Methods:

Materials

Drug: Captopril.

Excipients: Chitosan, hydroxy propyl methyl cellulose (HPMC), methyl cellulose, citric acid, sodium bicarbonate, lactose, talc, magnesium stearate, ethyl cellulose, polypropylene foam powder etc. Equipments:

1. Dissolution test apparatus2. Disintegration test apparatus3. UV spectrophotometer4. Monsanto hardness tester5. Roche friabilator6. Electronic balance7. Single pan digital balance8. Tablet punching machine9. Sieves10. FTIR spectrophotometer & DSC.

Methods:

Captopril floating tablets will be prepared by one of the following method.

1. Direct compression method: In this method drug, polymers and other additives were weighed accurately and mixed well to get uniform mixture and thus obtained blend is compressed by using 10 station rotary tablet punching machine. (Clit Ahmedabad).

2. Hot melt extrusion method: In this method, a mixture of drug, polymers, thermal lubricants, sodium bicarbonate and/or MCC was first blended. The blended powder

was placed in the hopper of single- screw extruder and extruded at different temperatures. After melt processing, the extrudates were cool at room temperature for 48 hours and then manually cut into tablets.

3. Effervescent technique: In this method, a drug mixed with polymer, gas generating agent and other excipients. Isopropyl alcohol was added drop wise then wet mass was passed through sieve 40#. Dry the granules at room temperature for 1 hour and then blended with talc and magnesium stearate and compressed in rotary tablet compression machine.

7.3 Evaluation parameters: (pre and post compressional)32, 33.

1. Bulk density and tap densities: Exactly 50 gm of powder blend will weigh on chemical balance and transferred into a 100 ml measuring cylinder. The cylinder was dropped on a wooden platform from a height of 2.5 cm three times at 2 seconds interval. The volume occupied by the granules will record as the bulk volume. The cylinder will then tap on the wooden platform until the volume occupied by the powder blend remained constant. This will repeat three times for granules. The data generated will use in calculating the Carr’s compressibility index and Hausner’s ratio.

2. Angle of repose: 50 gm of the powder blend will placed in a plugged glass funnel which had a distance of 10 cm from the flat surface. The granules will then allow to flow through the 8 mm funnel orifice by removing the cotton plug from the funnel orifice. The height of the heap (h) formed as well as the radius of the heap (r) will noted.

3. Tablet thickness: The thickness of 10 tablets each selected at random from the formulated tablets will determine using a vernier caliper and the mean of these readings will taken as the mean tablets thickness.

4. Tablet weight uniformity: Twenty tablets will weigh individually using a digital balance with the precision of 0.05 mg and readability of 0.1 mg, from which the mean will calculate and percentage deviations determine.

5. Hardness (Crushing strength): The crushing strengths of tablets will determine individually with the Monsanto hardness tester, following 10 tablets will use and the mean crushing strength will calculate.

6. Friability: The friability of 10 tablets will determine using Roche friabilator (Electrolab, Mumbai). This device subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at 25 rpm and dropping the tablets at a height of 6 inches in each revolution. Preweighed sample of tablets will place in the friabilator and will subject to 100 revolutions. Tablets will dedust using a soft muslin cloth and reweigh.

7. Disintegration test: The disintegration time of tablets will determine according to the method described in the British Pharmacopoeia 1998. Six tablets will place in

each compartment of the disintegration apparatus, with water thermostated at 37 ± 10

C as the medium. The tablets will consider to have passed the test after the 6 tablets passed through the mesh of the apparatus.

8. Drug content uniformity: The drug content of the matrices will determine in triplicate by equilibrating an accurately weigh quantity of the Captopril in appropriate dissolution medium. The samples will filter, suitably diluted and assayed spectrophotometrically.

9. In-vitro dissolution studies: Release of drug, from the bi-layer tablet will determine by using USP paddle method. The dissolution rate will study using 900 ml appropriate dissolution medium and scanned in the UV-Visible spectrophotometer.

10. Drug polymer interaction study: The drug and different polymers will be used in this research work. There will be a chance of interaction between drug and polymer. To know any interaction between drug and polymer we planned to check it by FTIR and DSC studies.

11. Swelling index: The individual tablets were weighed accurately and kept in 50 ml of double distilled water. Tablets were taken out carefully after 60 minutes, blotted with filter paper to remove the water present on the surface and weighed accurately. Percentage swelling index (SI) was calculated by using the formula SI = (Wet weight – Dry weight / Dry weight) X 100.34

12. Buoyancy determination: Floating time was determined by using USP 24 dissolution apparatus 27 at 100 rpm using 900 ml of 0.1N HCL and temperature was maintained at 37 ± 0.50 C throughout the study. The duration of floating (floating time) is the time the tablet floats in the dissolution medium (including buoyancy lag time).

13. Stability studies: On selected fabricated tablets will strip pack and kept at 450 C with 75% RH. Samples will withdraw at 0, 15, 30 and 45 days for evaluation of appearance, drug content and in- vitro drug release.

7.1 Source of data:a) Internet.b) Gulbarga University Library, Gulbargac) RGUHS (Helinet).d) International Pharmaceutical Abstracts.

7.2 Method of Collection of data: The data for the study is planned to collect from the laboratories based on experiment which include the following:

- Formulation and development of floating matrix tablets containing Captopril.- Evaluation of floating matrix tablets with respect to content uniformity, floating

capacity, water uptake study and in vitro dissolution study. - Evaluation of floating matrix tablets with respect to various physical parameters.

7.3 Does the study require any investigation to be conducted on patients or other humans or animals? If so, please describe briefly.

Not under the plan of the work7.4 Has ethical clearance been obtained from your institution in case of 7.3

Not applicable

8. List of References:

1) Ichikawa M, Watanake S, Yake YM. A new multiple unit oral floating dosage systems: Preparation and in-vitro evaluation of floating and sustained release characteristics. J. Pharm. Sci. 1991; 80:1062-6.

2) Yeole PG, Khan S, Shah K. Floating drug delivery systems: Need and development. Int. J. Pharm. Sci. 2005; 67:265-72.

3) Chavanpatil MD, Jain P, Chaudhari S, Shear R, Vavia PR. Novel sustained release, swellable and bioadhesive gatroretentive drug delivery system for Ofloxacin. Int. J. Pharm. 2006; 316:86-92.

4) Singh BN, Kim KH. Floating drug delivery systems: An approach to oral controlled drug delivery via gastric retention. J Control Release. 2000; 63:35-259.

5) Hwang SJ, Park K. Gastric retentive drug –delivery systems. Crit Rev Ther Drug Carrier Syst. 1998; 15:243-84.

6) Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms: Overview and special case of Helicobactor pylori. J. Control Rel. 2006; 111:1-18.

7) Rouge N, Buri P, Doelkar E. Drug absorption sites in the gastrointestinal tract and dosage for site-specific delivery. Int. J. Pharm. 1996; 136:117-39.

8) Umamaheshwari RB, Jain S, Bhadra D, Jain NK. Floating microspheres bearing acetohyxamic acid for the treatment of Helicobactor pylori. J. Pharm. Pharmacol. 2003; 55:607-13.

9) Jain SK, Awasthi AM, Jain NK, Agrawal GP. Calcium silicate based microspheres of rapiglinide for gastroretentive floating drug delivery: Preparation and in vitro characterization. J Control Rel 2005; 107:300-9.

10) Garg S, Sharma S. Gastroretentive drug delivery systems. Business Brief Pharmatech 5th ed. Available from: http://www.touchbriefings.com/cdps/ cditem. cfm? NID-17andCID-5. [cited in 2003].

11) Jacson EK. Renin and angiotensin. In: Hardman JG. Limbird LE editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. USA: McGraw-Hill: 2001.p.821-2.

12) C. Dollery, Therapeutics Drugs, Churchill Living stone, New York 1999, pp. c38–c43.

13) N. H. Anaizi and C. Swenson, Instability of Captopril solution, Am. J. Hosp. Pharm. 50 (1993) 486–488.

14) Y. Seta, Y. Kawahara, K. Nishimura and R. Okada, Design and preparation of captopril sustained release dosage forms and their biopharmaceutical properties, Int. J. Pharm. 1988; 41:245–254.

15) Basak SC, Rao KN, Manavalan R, Rao PR. Development and in vitro evaluation of an oral floating matrix tablet formulation of Ciprofloxacin. Indian J. Pharm. Sci. 2004; 66(3): 313-316.

16) Rahman Z, Ali M, Khar RK. Design and evaluation of bilayer floating tablets of captopril. Acta Pharm.2006; 56:49-57.

17) Patel VF, Patel NM. Self Correcting Monolithic floating matrix tablets of Dipyridamole: Influence of formulation variables. Indian Journal of Pharmaceutical Sciences. 2007:219-225.

18) Jaimini M, Rana AC, Tanwar YS. Formulation and evaluation of Famotidine floating tablets. Current Drug Delivery. 2007;04:51-55.

19) Patel DM, Patel NM, Pandya NN, Jogani PD. Formulation and optimization of Carbamazepine floating tablets. Indian Journal of Pharmaceutical Sciences. 2007:763-767.

20) Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. Fabrication and evaluation of Levofloxacin hemihydrate floating tablet. Research in Pharmaceutical Sciences 2008; 3(2): 65-72.

21) Sharma S, Sharma A, Jha KK. The study of Captopril floating matrix tablets using different polymers as release retarding agent. The Pharma Research. 2009;01:34-40.

22) Prajapati ST, Patel LD, Patel DM. Studies on formulation and in vitro evaluation of floating matrix tablets of Domperidone. Indian Journal of Pharmaceutical Sciences. 2009:19-23.

23) Havaldar VD, Kulkarni AS, Dias RJ, Aloorkar NH, Mali KK. Floating matrix tablets of atenolol: Formulation and in vitro evaluation. Asian Journal of Pharmaceutics. 2009:286-291.

24) Danki LS, Sayeed A, Kadam S, Salger S. Formulation and evaluation of floating tablet of Alfuzosin hydrochloride. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2010; 1(3): 108-130.

25) Zawar LR, Savaliya PJ, Bari SB, Gattani SG. Formulation and evaluation of floating – mucoadhesive tablet of Clarithromycin. International Journal of Pharma. and Bio. Sciences. 2010; 1(2):01-10.

26) Yadav A, Jain D. Formulation and characterization of gastroretentive floating

microballoons of Metformin. Int. J.Phrma Sci. Res. 2010;1(3):38-43.

27) Kumar R. Development and in vitro evaluation of sustained release floating matrix tablets of Metformin hydrochloride. Int. J.Phrma Sci. Res. 2010; 1(8): 96-101.

28) Yadav S, Singh A, Shingala V, Selvam P, Kavitha K. Formulation and evaluation of floating tablets of Ranitidine hydrochloride using natural and synthetic polymers. The Pharma Research. 2010; 3:221-231.

29) Shinde AJ, Waghule AN, Paithane MB, More HN. Formulation and in vitro evaluation of sustained release floating tablet of Cephalexin using hydrophilic polymers. International Journal of Pharmacy and Pharmaceutical Sciences. 2010; 1(2): 58-65.

30) Gupta SK, Gupta U, Omray LK, Yadav R, Soni VK. Preparation and characterization of floating drug delivery system of Acyclovir. International Journal of Applied Pharmaceutics. 2010; 2(3): 7-10.

31) Narasaiah VL, Saravanan G, Kumar MR, Reddy BK, Srikanth P, Kumar MS, Satyanand S, Ashok A. Formulation, characterization and in-vitro evaluation of Sumatriptan succinate floating tablets. JITPS. 2010; 1(5): 191-203.

32) Indian Pharmacopoeia, The Controller of Publications, Delhi, 1996; 1:735.

33) Lachman L, Liberman HA and Kanig JL: The Theory and Practice of Industrial Pharmacy, 3rd Edn. Varghese Publishing House, Mumbai, 1991; 88

34) Chavanpatil MD, Jain P, Chaudhari S, Shear R, Vavia PR. Development of sustained release gatroretentive drug delivery system for Ofloxacin. Int. J. Pharm.2005; 304:178-184.

35) Rosa M, Zia H, Rhodes T. Dosing and testing in-vitro of a bioadhesive and floating drug delivery system for oral application. Int. J. Pharm. 1994;105:65-70.

9. Signature of candidate

10. Remark of the guide

11. 11.1 Name & Designation of Guide

Prof. Basawaraj S. Patil M. Pharm. (Ph.D)ProfessorDepartment of PharmaceuticsR.M.E.S.’s College of Pharmacy, Gulbarga-585102.

11.2 Signature

11.3 Co-Guide Mr. Upendra Kulkarni, M. Pharm. (Ph.D)Lecturer,Department of PharmaceuticsR.M.E.S.’s College of Pharmacy, Gulbarga-585102.

11.4 Signature

11.5 Head of the Department Prof. Hariprasanna R. Chitapurkar M. Pharm. (Ph.D)Professor & Head Department of PharmaceuticsR.M.E.S.’s College of Pharmacy, Gulbarga-585102.

11.6 Signature

12. 12.1 Remark of the Director/

Principal

We will provide all the necessary facilities required for the proposed research work.So, recommended for registration.

12.2 Signature

Prof. Kishoresingh K. Chatrapathi ,M. Pharm..Ph.D. Director/Principal

R.M.E.S.’s College of Pharmacy, Gulbarga-585102.