FORMULATION AND EVALUATION OF VALSARTANFAST DISINTEGRATING TABLETS USING SOLID DISPERSION TECHNIQUE

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY

PENJARLA RAVITEJA
M.PHARM, PART- I

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Dr.S.MURALIDHAR, M. Pharm, M.Phill, Ph.D.

Professor

Department of Pharmaceutics

Dr. H.L.T College of Pharmacy,

Kengal, Channapatna-562 161

2011-2012.

Rajiv Gandhi University of Health SciencesBangalore, Karnataka

AnneXUre II

Proforma for Registration of subjects for Dissertation

1. / Name of the Candidate and
Address (in Block Letters) / PENJARLA RAVITEJA M. PHARM, PART-I DEPARTMENT OF PHARMACEUTICS Dr. H. L. T.COLLEGE OF PHARMACY. KENGAL, CHANNAPATNA-562161 RAMANAGARAM (DIST), KARNATAKA
2 / Name of the Institution /

Dr. H. L. T.COLLEGE OF PHARMACY. KENGAL, CHANNAPATNA-562 161 RAMANAGARAM (DIST), KARNATAKA

3 / Course of the Study and Subject /

MASTER OF PHARMACY IN PHARMACEUTICS

4 / Date of Admission to the Course / 20/6/2011
5 /

Title of the Topic

/ “ FORMULATION AND EVALUATION OF VALSARTAN FAST DISINTEGRATING TABLETS USING SOLID DISPERSION TECHNIQUE”
YNTESIS

6.0 BRIEF RESUME OF THE INTENDED WORK

6.1NEED FOR THE STUDY

Oral administration is the most popular route among all the routes due to ease of ingestion, pain avoidance, versatility (to accommodate various types of drug candidates) and most importantly patient compliance1.Recent developments in mouth dissolving /disintegrating tablets have brought convenience in dosing to elderly and children who have trouble in swallowing tablets2and which leads to improved patient compliance.Oro-dissolving tablets are gaining prominence as new drug delivery systems. These dosage forms disintegrate or dissolve in oral cavity within a minute, without need of water or chewing, which significantly increases the bioavailability than those observed from the conventional tablet dosage forms.Several approaches have been employed to formulate fast disintegrating tablets involving tablet molding, freeze drying, sublimation, spray drying, disintegrant addition- direct compression, and use of sugar based excipients3-4.

Orally disintegrating tablets offer all advantages of solid dosage forms and liquid dosageforms along with special advantages. Which includes:

  1. As Fast disintegrating tablets are unit solid dosage forms, they provide good stability, accurate dosing,easy manufacturing, small packaging size and easy to handle by patients5.
  2. No risk of obstruction of dosage form, which is beneficial for travelling patients whodo not have access to water.
  3. Easy to administer for institutionalized patients (especially for mentally retarded andpsychiatric patients).
  4. High drug loading is possible.
  5. Bioavailability of drugs that are absorbed from mouth pharynx and esophagus is increased.6.
  6. Leave minimum or no residue in the mouth after oral administration.
  7. Guarantee a rapid onset of action when required7.
  8. First pass metabolism of drugs avoids which reduces the dose and increase thebioavailability.

Fast onset of action is a major concern in the treatment of hypertension.The problem of slow onset of action of drugs can be overcome by development of fast disintegrating mouth tablets are best suitable8. Valsartan is an antihypertensive drug belongs to the category of angiotension ll receptor antagonist.It is a poorly soluble drug. So, to overcome this problem, an effort is being made in the present work to formulate and evaluate the optimized formulation of a Fast disintegrating tablet containing Valsartan.

6.2 REVIEW OF LITERATURE

  1. S.Palanichamy9et.al. worked on the formulation development and evaluation of “Fast Dissolving Theophylline Tablets” using super disintegrants namely crospovidone,sodium starch glycolate and pre gelatinized starch with three concentrations(2%,3%,and5%) are prepared by direct compression method.Among these formulations crospovidone 5% was to be the best formulation.
  1. B.S.Kuchekar10et.al.Workedonthedispersibletabletsusing natural substance as disintegrants such as ispaghula husk powder, cassia tora powder, cassia tora powder(defatted), cassia nodosa powder in different concentration by direct compression method.Formulations were evaluated for the standard of dispersible tablets and were compared with marketed products.5% ispaghula husk shows betterdisintegration as compared to marketed.
  1. Bhalerao AV11et.al. worked on the “Development and evaluation of clonazepam fastdisintegrating tablets using superdisintegrants and solid dispersion technique”. The drugis poorly water soluble therefore to enhance the solubility and release of drug, soliddispersion of DRUG and PVP K30 was prepared by solvent evaporation method.Different combinations of superdisintegrants such as crosscarmellose sodium, sodium starch glycolate, crospovidone were used. Directly compressible mannitol andaspartame were used to enhance the mouth feel and taste. Lactose was used asdiluents. The tablets were prepared by direct compression technique on rotary tabletmechine. Amongst all DRUG : PVP K30 (1:4) ratio and combination of 5% w/wcroscarmellose sodium and 5% w/w of sodium starch glycolate showed leastdispersion time of 8 seconds and faster dissolution.
  2. Nitin Chandrakant Mohire12et.al. worked on the “Development of Metronidazole orodispersible tablets” by using three different techniques of taste masking, such additionof sweetener, formation of complex and numbness of tongue, and three different disintegrating agents such as sodium starch glycolate (SSG), Bamboomanna (BM), chitosan (CHN) and combination thereof. Among all the combination of SSG: BM and SSG: CHN in ratio 1:1 showed good result.
  1. P.V.Swamy13 et.al.were studiedDesigned orodispersible tablets of meloxicam using combination ofsuper-disintegrants i.e., sodium starch glycolate – croscarmellose sodium or sodium starch glycolate – crospovidone. Among the two formulations, the formulation prepared by direct compression method using 2% w/w sodium starch glycolate and1.5% w/w croscarmellose sodium was found to be a better formulation.
  2. Muralidhar.S14. et.al. worked on“Enhancement of dissolution rate of etoricoxib through

solid dispersion Technique.” using PEG 6000 as carrier at various proportions by using different techniques likePhysical mixtures, Kneading Method and Solvent Evaporation Method. it can be seen that the dissolution of Etoricoxib increases withincrease in PEG 6000 up to 1:4 ratio of drug: PEG 6000.

6.3 MAIN OBJECTIVES OF THE STUDY

1.To develop Fast disintegrating tablet contains valsartan drug by using solid dispersion technique with superdisintegrantslikeSodiumstrach glycolate, Croscarmellose sodium, Crospovidone, etc. alone orwith combinations.

2.To evaluate the pre-compression characteristics of powder mixtures, like Bulk density, Flow property, Angle of Repose, Compressibility index etc.

3.To evaluate the post-compression characteristics of the tablet like Hardness, Friability, Disintegration time, Wetting time and Dispersion time etc.

4.To carry out in-vitro Dissolution studies.

5.Charecterzation of drug interaction with polymers by FTIR and DSC.

6.To carry out stability studies according to ICH guidelines, for optimized formulation.

7. MATERIALS AND METHODS:

7.1SOURCE OF DATA

The preliminary data required for the experimental study is obtained from-

  1. CD-Rom search available at National Center for Scientific Information (NCSI), Indian institute of Sciences, Bangalore,
  2. Dr. H.L.T. College of Pharmacy Library,
  3. Scientific abstracts,
  4. Journals,
  5. Internet sources and Relevant Books.
  6. The data will be collected by Laboratory investigation and will be recorded.

7.2.METHODS OF COLLECTION OF DATA

  1. The selected drug will be characterized and evaluated for its physicochemical properties like solubility and compatability with excipients.
  2. To identify the suitable excipients alone or in combination for further processing.
  3. To carry out preformulation studies like organoleptic properties, bulk density, tapped density, angle of repose, compressibility index of the powder mixture (drug and excipients).
  4. To formulate various formulations of solid dispersions of drug with different ratio of the superdisintegrant alone or in combination.
  5. The optimized solid dispersion was then converted into tablets by using wet granulation,dry granulation or direct compression method.
  6. To evaluate the compressed tablet for hardness, friability, disintegration time, wetting time, in-vitro dispersion time and in-vitro dissolution time, etc.
  7. Charecterzation of drug interaction with polymers by FTIR and DSC.
  8. The data so obtained will be subjected for statistical analysis.
  9. Optimize formulation will be subjected to stability studies according to ICH guidelines

7.3 Does the study require any investigations or interventions to be conducted on

patients or other humans or animals? If so please describe briefly.

NOT APPLICABLE

7.4.Has ethical clearance been obtained from your institution in case of 7.3?

NOT APPLICABLE

  1. LIST OF REFERENCES:
  1. Seager H. studied Drug-delivery products and the zydis fast-dissolving dosage form J.pharm pharmacol, 1998; 50:375-82.
  1. Habib W., Khankari RK, Hontz J. studied Fast-dissolve drug delivery systems. crit Rev. Ther. Drug Carrier Sys2000; 17:61-72.
  1. Dobetti L. studiedFast disintegrating tablets. US Patent, 2003; 6:596,311.
  1. Brown D. studied Orally disintegrating tablets-taste over speed. Drug Del tech, 2003; 3:58-61.
  1. Jaccard TT, Leyder et.al. IUne nouvelle forme galenique Ie Iyoc. Ann Pharm Fr, 1985; 43: 123-31.
  1. G, Chevanne F, Le Corre P, Chemtob C, Le verge R, Bioavailibility of Phloroglucinol in man .J.pharm Belg,1999;54:75-82.
  1. Gafitanu E, Dumistracel I. Antochi S, Formulations and bioavailability of Propyphenazone in lyophilized tablets. Rev Med Chir Soc Med Nat lasi, 1991; 95:127-8.
  1. Sandipan Kundu, P.K Sahoo.Recent trends in the developments of orally disintegrating tablet technology.Pharma Times ,2008;40(04):11-20.
  1. S.Palanichamy, C.Prabhu, M.Rajesh,Fast dissolving tablets of Theophylline Tablets.. Research Journal of Pharmacy and Technology, 2011;4(5):793-797.
  1. B.S.Kuchekar, S.R. Pattan Formulation and evaluation of Isoniazide dispersible tablets using natural substances as disintegrants. Research Journal of Pharmacy and Technology,2009;2(3):585-589.
  1. Bhalerao AV, Deshkar SS, Gharge VG and Deshpande AD. Development and evaluation of Clonazepam fast disintegrating tablets using superdisintigrates and solid dispersion technique. Research Journal of Pharmacy and Technology, 2 (2); 2009; 04: 375-377.
  1. Nitin Chandratant Mohire, Adhikrao Vyankatrao Yadav, Vaishali Kondibhau Gaikwad.

Novel Approaches in Development of Metronidazole Orodispersible Tablets. Research Jouurnal of Pharmacy and Technology.2 (2): 2009; 04: 283-286.

  1. P.V.Swamy, S.H.Areefula, S.B. Shrisand, Smitha Gandra and B. Prasanth. Oro-dispersiblr tablets of meloxicam using disintegrant blends for improved efficacy. Indian Journal of Pharmaceutical Sciences; 2007; 11: 836 – 839.
  1. S.Muralidhar,G.Devala Rao, M Krishna Murthy and K.Kiran Kumar. Enhancement of Dissolution rate of Etoricoxibthrough solid dispersion technique.Journal of Applied Pharmaceutical Science;2011; 1(05);129-132.
  2. B.Raju Patel,Dhaval Patel,Rampesh Parmar.Development and Invitro evaluation of fast dissolving tablets of Glipizide.International Journal of Pharmacy and pharmaceutical Sciences;2009;1(12):145-150.
  3. S. Jeevanandan, D. Dhachinamoorthi, formulation and evaluation of Naproxem sodium orodispersible tablets-A Sublimation technique,Asian Journal of Pharmaceutics, 2010:4:48-51.
  1. Indhumathi d, Grace Rathnam,Design and optimization of orodispersible tablets of antidepressant drug by superdisintigrants addition method,International Journal of Pharmaceutical Sciences Review and Research,2010;2(2):1-9.
  1. Vineet Bhardwaj,Mayank BansalFormulation and Evaluation of fast dissolving tablets of Amlodipine Besylate Using Different Super Disintegrants and Camphor as Sublimating Agent. American-Eurasian Journalof Scientific Research,2010;5 (4): 264-269.
  1. Modasiya M.K., Lala I.I.,Design and characterization of fast disintegrating tablets of Piroxicam, International Journal of Pharmtech Research, 2009; 1(2):353-357.
  1. S.B.Shirsand, Sarasija Suresh,Design of fast disintegrating tablets of Prochlorperazine maleate by effervescence method, Indian Journal of Pharmaceutical Sciences, 2009;71(4): 447-451.
  1. Ganesh kumar Gudas, B.Manasa, V.V.Rajesham.Formulation and evaluation of fast dissolving tablets of Chlorpromazine HCl,Journal of Pharmaceutical Science and Technology,2010; 2(1):99-102.
  1. Shishu, varun rishi kapoor, kamal preet,Taste masking and formulation of Ofloxacin rapid disintegrating tablets and oralsuspension. Indian Journal of Pharmaceutical Research,2009; 43 (2); 04:150-155.

9 / Signature of the candidate
10 / Remarks of the Guide / Topic selected for Dissertation work is satisfactory. This can be carried out in our Laboratory.
11 / Name and Designation of the guide
(In Block Letters)
11.1Guide / Dr.S.MURALIDHAR, M. Pharm, M. Phill, Ph.D.
PROFESSOR DEPARTMENT OF PHARMACEUTICS Dr. H. L. T. COLLEGE OF PHARMACY, KENGAL, CHANNAPATNA-562 161, RAMANAGARAM (DIST), KARANATAKA.
11.2Signature
11.3Co – Guide
(If any)
11.4Signature
11.5Head of the Department / Dr.R.RAMESH, M. Pharm, Ph.D.
PROFESSOR DEPARTMENT OF PHARMACEUTICS Dr. H. L. T. COLLEGE OF PHARMACY, KENGAL, CHANNAPATNA-571 502, RAMANAGARAM (DIST), KARANATAKA.
11.6Signature
12 / 12.1Remarks of the Chairman and Principal / The above mentioned information is correct and recommend the same for approval.
12.2Signature

From

PENJARLA RAVITEJA,

M.PharmPart – I

Dr.H.L.T College of Pharmacy,

Kengal, Chennapatna.

To

The Registrar (Evaluation), Rajiv Gandhi University of Health Sciences, 4th ‘‘T’’ Block, Jayanagar, Bangalore-560 041.

(Through Proper Channel)

Sub: Resubmission of Synopsis of Dissertation – reg

Respected Sir,

Herewith, I am submitting synopsis of dissertation work “FORMULATION AND EVALUATION OF VALSARTAN FAST DISINTEGRATING TABLETS USING SOLID DISPERSION TECHNIQUE” for registration in M.Pharm (Pharmaceutics) of Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka.

Kindly accept the same and oblige.

Thanking you,

Yours Faithfully,

(PENJARLA RAVITEJA)

Place: Channapatna

Date: 14.12.2011

Guide:

Dr.S.MURALIDHAR, M. Pharm, M. Phil, Ph.D. Dr. R. Ramesh, M. Pharm, Ph.D. Professor Principal

Department of Pharmaceutics Dr.H.L.T.College of Pharmacy,

Dr.H.L.T.College of Pharmacy, Kengal, Channapatna-562161

Kengal, Channapatna-562 161 Ramanagaram (Dist), Karnataka.

Ramanagaram (Dist), Karnataka.

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