“FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF RAMIPRIL”

M.PHARM. DISSERTATION PROTOCOL

Submitted to

Rajiv Gandhi University of Health Sciences

Bangalore, Karnataka.

By

Mr. WaghmareTusharBibhishan

Under the Guidance

Of

Mr. K. PrakashReddy M.Pharm,

DEPARTMENT OF PHARMACEUTICS

SVET’s COLLEGE OF PHARMACY

Humnabad - 585330

2011-2012

Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name and Address of the candidate / WaghmareTusharBibhishan
At:BabhalgaonPO:Dahiphal
Tq:KallamDist:Osmanabad
Maharashtra. 413525
2. / Name of the Institution / SVET’s College of Pharmacy,
Humnabad– 585330 Karnataka.
3. / Course of study and subject / Master of Pharmacy in Pharmaceutics.
4. / Date of admission to course / 21th Dec. 2011
5. / Title of the topic / Formulation and Evaluation of Fast Dissolving Tablets of Ramiprilusingsuperdisintegrants.
6. / Brief resume of the intended work
6.1 Need of the study:-
As pharmaceutical scientists are attending a better understanding of biochemical and physicochemical properties related to the action, the drug delivery systems are becoming simple. Fast dissolving tablets are popular due to better patient compliance and are preferred over conventional capsules and tablets.[1]
The preparation of the formulation of poorly water soluble drug has always been a challenging problem faced by pharmaceutical scientists and it is expected to increase because approximately 40% or more of the new chemical entities being generated through drug discovery programs have problem in water solubility.[2]
Most commonly used methods to prepare these tablets are freeze-drying lyophilization, tablet molding and direct-compression methods. Lyophilized tablets show a very porous structure which causes quick penetration of saliva in to the pores when placed in oral cavity.[3]
Mouth dissolving tablets should give fast disintegration, dissolution, ease of swallowing, onset of action.[4]
Ramiprilacts as anangiotensin-converting enzyme (ACE) inhibitor, used to treathigh blood pressureandcongestive heart failure.The half life of the drug is 2-4 hours with 28% bioavailability. The dose of ramipril is 1.25-10 mg/day.[5]
Fast dissolving tablet formulation has been widely and successfully applied to
improve thedissolution, solubility, and consequently the bioavailability of poorly
watersoluble drugs. Because of its poor aqueous solubility, ramipril may pose
dissolution related absorptionproblem. In the present study, an attempt will be made
to prepare fast dissolving tablets of ramipril in the oral cavity with enhanced
dissolution rate & hence improved patient compliance
6.2 Review of Literature
  1. Nagendrakumar Det al6 have prepared fast dissolving tablets of granisetronHCl was prepared and evaluated for various evaluation test and concluded that formulation containing 4% w/w of co-processed superdisintegrants (1:1 mixture of crossprovidone and crosscarmellose sodium) was best formulation.
  1. Kalia Aetal7 have prepared oxcarbazepine of FDTs using crossprovidone as superdisintegrant by direct compression method and concluded that the drug released was found to be comparable to the marketed dispersible tablet.
  1. Barhate et al8 have prepared fast dissolving tablet of meloxicam by solvent evaporation method using super-disintegrants such as PEG - 4000 & PVPK 30.
  1. Parmar et al9 have prepared fast dissolving tablet of domperidone by direct compression method using Avicel PH 102 & sodium starch glycolate as super-disintegrant.
  1. Tekadeet al10have prepared rapidly disintegrating tablet containing taste masked metaclopropamide hydrochloride prepared by extrusion-precipitation method using super-disintegrants such as microcrystalline cellulose, crospovidone, croscarmellose sodium, sodium starch glycolate and eudragit as a masking agent.
  1. Raghavendra R et al11 have formulated fast dissolving tablet of Carbamazepine using wet granulation method. In this formulation, plantagoovata mucilage and seed powder is used as natural superdisintegrants. The formulation were tested, formulation containg 25%w/w showed best result.
  1. Patil BSet al12 have worked on formulation and evaluation of fast dissolving tablets of granisetronHCl. The FDTs were prepared using plantagoovatamucilage and sodium starch glycolate as superdisintegrants by direct compression method. Prepared tablets were evaluated for uniformity of weight, thickness, hardness, friability, drug content, wetting time and in-vitro dispersion time and in-vitro dissolution study.
  1. Patil BSet al13 were prepared fast dissolving tablets of tizanidineHCl using crosscarmellose sodium, sodium starch glycolate and crossprovidone as superdisintigrants. It was concluded that fast dissolving tablets could be prepared by direct compression method using different superdisintigrants enhanced dissolution will lead to improved bioavailability, improved effectiveness of tizanidineHCl.
  1. Gohil DYet al14 have prepared bambuterolHCl fast dissolving tablets using sodium starch glycolate, crossprovidone,crosscarmellosesodium and pregelatinised starch by direct compression method. The tablets were evaluated for uniformity of weight, thickness, hardness, friability, drug content, wetting time and in-vitro dispersion time and in-vitro dissolution study.
  1. Patil BSet al15 have worked on formulation and evaluation of FDTs of granisetronHCl by direct compression method. From this study it was concluded that FDTs could be prepared by direct compression method using different superdisintegrants enhanced dissolution will lead to improved bioavailability, improved effectiveness of granisetronHCl.
  1. Prakash Get al16have formulated fast disintegrating tablets of Granisetron HCL. In this formulation plantagoovata, gum karaya and agar was used as natural super disintegrants and Indion 234, croscarmellose sodium and crospovidone as synthetic superdisintegrants in different formulation. From the data obtained it was concluded that natural super disintegrants showed better release then most widely used synthetic super disintegrants.
  1. Nilesh Jetal17have formulated taste masked fast dissolving tablet of Ciprofloxacine using crospovidoneandsodiumstarchglycolateas superdisintegrating agent. In this formulation, vanilline was used as taste masking agent. From data obtained formulation containing 10%w/w of crospovidone shows better taste masking and faster disintegration then other formulation.
6.3 Objectives of the study
The present research investigation is planned with the following objectives.
1)To compare the effect of different techniques used to prepare fast dissolving tablets on disintegration time, wetting time, water absorption ratio and percent drug release.
2)To evaluate the formulations with respect to content uniformity, in vitro release studies, etc.
3)To characterize the formulation by instrumental methods like FTIR.
4)To formulate fast dissolving tablets of ramipril withsuper disintegrantsby different techniques using super disintegrating agents like Crospovidonecroscarmellose sodium and sodium starch glyacolate
5)To evaluate the formulations with respect to various physical parameters.
6)To perform the stability studies on promising formulations as per ICH guidelines.
7. / Materials and Methods:
7.1
7.2 / Sources of data:
A.Internet.
B. Library: S.V.E.T’s College of Pharmacy.
C. I.I.C.T. library, Hyderabad.
D. Gulbarga University library, Gulbarga.
E. International pharmaceutical abstract.
Materials:
Drug:-Ramipril
Synthetic super disintegrants:-Crospovidone, crosscarmellose, sodium starch
glycolate.
Equipments:-
  1. UV visible spectrophotometer 1800(Shimadzu).
  2. pH meter.
  3. Electronic balance (Shimadzu).
  4. USP tablet dissolution test apparatus (Electrolab TDT 08L).
  5. Rotary Tablet punching machine.
  6. Digital hardness tester.
Method for the preparation of fast dissolving tablet:-
a)Direct compression method: The entire ingredient were passed through # 60 mesh separately, weighed and mixed in geometrically order. Then lubricant and glidant (#200 mesh) were added and mixed for further 5 min. the blend thus obtained was directly compressible.
b)Effervescent technique: In this method, a mixture of sodium bicarbonate and anhydrous citric acid is included in order to further enhance disintegration and taste masking effect.
c)Sublimation: In this method, mannitol is used as a diluent and camphor as a volatile material to prepare highly porous compressed tablet. After compression, the tablet will be heated in hot air ovan at 500c until a constant weight is obtained to ensure the complete removal of volatilizable component.
d)Disintegrant addition: In this method superdisintigrant such as sodium starch glycolate, cross linked PVP, treated agar etc. will be included to obtain faster disintegration.
e)Use of sugar based excipients: In this method highly soluble sugar excipients such as sorbitol,dextrose,xylitol, fructose etc. are used in order to produce fast dissolving tablet with good taste masking.
Method of Collection of Data:
Various fast dissolving tablet formulation of ramipril with superdisintigrants will be designed and evaluated for hardness, friability, weight variation, disintegration time, drug content, in vitro dissolution rate ( in pH 6.8 phosphate buffer ) short term stability & drug excipent interaction (IR spectroscopy) .
  1. Estimation of drug content:-
The drug content of fast dissolving tablet will be determined by spectrophotometrically on the filtered extract of the drug.
  1. Disintegration time:-
Disintegration time of fast dissolving tablet will be determined by using distilled water at 37±2oC as the medium using tablet disintegration test apparatus USP.
  1. In vitro dissolution study:-
In vitro drug release study of prepared fast dissolving tablets will be carried out using 900ml of pH 6.8 phosphate buffers in USP dissolution test apparatus (Campbell. TDT-08L) using paddle stirrer at 50 rpm.
  1. Short term stability :-
The promising fast dissolving tablet of ramipril will be stored at temperature of 40±2oC and 75±5% relative humidity for 3 months and evaluated for drug content, disintegration time and drug excipient interaction (IR Spectroscopy).
7.3 / Does the study require any investigation to be conducted on patients, other
Humans or animals? If so, please describe briefly.
Not under the plan of work
7.4 / Has ethical clearance have been obtained from your institution in cases of 7.3?
Not applicable
List Of References :-
  1. Shobhit K, Gupta S, Sharma P. A review on recent trends in oral drug delivery system- fast dissolving formulation technology. Adv Bio Res 2012;6(1):6-13.
  2. Kumar N, Jain AK, Singh C, Agarwal K, Nema RK. Development, characterization and solubility study of solid dispersion of terbinafinehydrochloride. Int J PharmSci Nanotech. 2008; 1: 171-76.Deshmukh VN. Mouth dissolving drug delivery system: A review.IntJ Pharm Tech Res.2012;4(1):41221.
  3. Patwardhan S, Dhairya M, Upadhay N, Bodas K, Ranade A, Shrotiya S. Isolation, characterization and study of disintegration properties of mucilage from urginesindica, liliaceae IJPL Inventi journals.2012.
  4. [Updated 2012 05 June; cited 2012 18 May]. Available from;
  5. Nagendrakumar D, Para MS, Design of fast dissolving GranisetronHCl tablets using novel co-processed superdisintegrants. J. Biosci. Tech. 2009;1(1):8-14.
  6. Kalia A, Khurama S, Forrmulation and evaluation of mouth dissolving tablets of Oxcarbazepine. Int. J Pharm.Pharm Sci. 2009;1(1):12-23.
  7. Barhate SD,Shankhpal GA, Sharma AS, Nerkar PD. Formulation of fast dissolving tablets of meloxicam.J Pharm Res. 2009;2(4):646-50.
  8. Parmar RB, Baria AH, Tank HM, Faldu SD. Formulation and evaluation of domperidone fast dissolving tablet.Int J Pharm tech Res. 2009;1(3):483-7.
  9. Randale AS, Dabhi CS, Tekade AR, Belgamwar VS, Gattani SG, Surana SJ. Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method. ChemPharm Bull. 2010;58(4):443-8.
  10. Raghavendra R, Upendra K, Durga R, Suresh D. Formulation and evalution of fast dissolving tablet of carbamazepine using natural super disintegrantplantagoovata seed powder and mucilage. Int J Pharmacy Pharm Sci. 2010;2(2):71-4.
  11. Patil BS, DayakarRao K,Forrmulation and evaluation of fast dissolving tablets of Granisetron hydrochloride. Int J App Bio & Pharm. Tech. 2011;2(2):22-8.
  1. Patil BS, Kulkarni U,Forrmulation and evaluation of fast dissolving tablets of Tizanidine hydrochloride by direct compression method. J PharmSci & Bio Scientific Res. 2011;1(1):71-7.
  2. Gohil DY, Savaliya RP, Formulation and characterization of bambuterol hydrochloride fast dissolving tablet using various superdisintegrants. Int. J. Pharm. Sci. & res. 2011:2(1):84-9.
  3. Patil BS, DayakarRao K, Forrmulation and evaluation of granisetron hydrochloride by direct compression technique. Int. J. Curr. Pharm. Res. 2011; 3(2):124-8.
  4. Prakash G, Doddayya H, Spandana D, Reddy S. Development and evalution of fast disintegrating tablets of Granisetron HCL with natural and synthetic polymers. Asian J Pharm Res 2011;1(3):72-77.
  5. Nilesh J, Suman M, Jitendra B, Surendra J. Effect of superdisintegrants on formulation of taste masked fast disintegrantingciprofloxacine tablets. Int Current Pharm Journal. 2012;1(4):62-67.

9. / Signature of the Candidate / WAGHMARE TUSHAR BIBHISHAN
10. / Remark of the Guide / The fast dissolving tablet of ramipril has the definite advantages in improving the patient compliance and increasing the bioavailability with improved efficacy.
11. / 11.1 Name & Designation of the Guide / Mr. K. Prakash Reddy
Asst. Professor
Department of Pharmaceutics,
SVET’s College of Pharmacy,
Humnabad-585330
11.2 Signature of Guide
11.3 Co-Guide
11.4 Signature Co-Guide
11.5 Head of the department / Dr. D. Nagendrakumar M.Pharm.Ph.D.
Department of Pharmaceutics,
SVET’s College of Pharmacy,
Humnabad-585330.
11.6 Signature of HOD
12. / 12.1 Remark of the
Principal
12.2 Signature / Dr. Nagendrakumar D.M.Pharm.Ph.D.
Department of Pharmaceutics,
SVET’s College of Pharmacy,
Humnabad-585330.

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