FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF OLANZAPINE

M.PHARM. DISSERTATION PROTOCOL

Submitted to

RajivGandhiUniversity of Health Sciences

Bangalore, Karnataka.

By

Mr. DESHMUKH RISHIKESH RAMAKANTB.Pharm.

Under the Guidance

of

Mr.K Prakash ReddyM.Pharm.

DEPARTMENT OF PHARMACEUTICS

SVET’s COLLEGE OF PHARMACY

Humnabad - 585330

2012-2013

Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name and Address of the candidate / DESHMUKH RISHIKESH RAMAKANT
A/P. KURDUWADI Tal. MADHA Dist.SOLAPUR
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 / 2ND AUGUST 2012
5. / Title of the topic / Formulation and Evaluation of Fast Dissolving Tablets of OLANZAPINE
6. / Brief resume of the intended work
6.1 Need of the study
Recent advances in novel drug delivery systems aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. One such approach leads to development of fast dissolving tablets. Fast disintegrating tablets (FDTs) are recent developments to present viable dosage alternative for patients who have difficulty in swallowing. FDTs are the products that disintegrate rapidly in the saliva without the need of drinking water. These are a perfect fit for the entire patients1.
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 cavity2. The main disadvantages of tablets produced are, in addition to the cost intensive production process, a lack of physical resistance in standard blister packs and their limited ability to incorporate higher concentrations of active drug. Molded tablets dissolve completely and rapidly3. However, lack of strength and taste masking are of great concern. Main advantages of direct compression are low manufacturing cost and high mechanical integrity of the tablets4.
Olanzapine is an oral Antipsychotic agent used mainly for treatment of Psychotic disorder & bipolar disorder. The half life of the drug is 21-54 hours5.
Hence, in the present research work Fast dissolving tablets of Olanzapine will be prepared by different techniques. Effect of various methods on dissolution rate, disintegration time and wetting time will be studied.
6.2 Review of Literature
  • Nagendrakumar Detal.,[6] have prepared fast dissolving tablets of granisetron HCland 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.
  • Jain CPe. al.,[7] have prepared fast dissolving tablets of valsartan using different superdisintegrants by direct compression method. Prepared FDTs were evaluated for physico-chemical properties and in-vitro dissolution and concluded that the drug released from FDTs increased with increasing concentration of superdisintegrants and was found to be highest with formulations containing crospovidone.
  • Gudas GK et al.,[8] have prepared fast dissolving tablets of chlorpromazine HCl by direct compression method using superdisintegrants such as sodium starch glycolate, crospovidone, croscarmellose sodium, L-HPC and pregelatinised starch. The prepared tablets were evaluated for hardness, friability, disintegration time, dissolution rate and drug content.
  • Jain SK et al.,[9] have prepared the mouth dissolving tablets of ibuprofen by solid dispersion technique using PEG 4000 as carrier and tween 80 as a surfactant in different ratios of carrier, drug and surfactant 5:5:1, 10:5:1, 25:5:1, 35:5:1 and 45:5:1 along with superdisintegrant. The tablet containing Ac-Di-Sol (12%) showed fast disintegration (202 seconds) and a drug release (84.57%) than commercial tablet.
  • Gohil DY et al.,[10] have prepared fast dissolving tablets of bambuterol hydrochloride with four superdisintegrants e.g., sodium starch glycolate, crospovidone, croscarmellose sodium and pregelatinized starch by direct compression method. Among all formulations, batch D4 (Containing 12% crospovidone) was considered as best formulation.
  • Manjunatha KMet al.,[11] have designed mouth dissolving tablets of olanzapine using different superdisintegrants namely, crospovidone, croscarmellose sodium and sodium starch glycolate. The optimized formulation containing 4% w/w crospovidone showed minimum disintegration time (10 seconds) and an almost complete release of the drug within five minutes.
  • Lakshmi PK et al.,[12] have formulated fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit®Epo and optimization through Taguchi orthogonal experimental design.The optimized films disintegrated in less than 30 seconds, releasing 96% of drug within 2 mins.
  • VishwakarmaD etal.,[13] have formulated and evaluated fast dissolving tablets of metoprolol tartrate. Disintegration time increased with increased in the level of croscarmellose sodium while it decreased for crospovidone, the release was dependent on the aggregate size in the dissolution medium.
6.3Objectives of the study
The present research investigation is planned with the following objectives.
1)To formulate fast dissolving tablets of Olanzapine by different techniques by using super disintegrating croscarmellose sodiumand crospovidone, etc.
2)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.
3)To evaluate the formulations with respect to various physical parameters.
4)To evaluate the formulations with respect to content uniformity, in vitro release studies, etc.
5)To characterize the formulation by instrumental methods like FTIR, DSC studies.
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. Gulbarga University library, Gulbarga.
C. I.I.C.T. library, Hyderabad.
D. S.V.E.T’s College library,Humnabad.
E. International pharmaceutical abstract.
Materials:
Drug:-OLANZAPINE
Natural disintegrants:-Hydroxy propyl methyal cellulose Carboxy methyal cellulose.
Poly vinyal alchol
Croscamellose
Sodium crospavidone
Talc
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 ingredients 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 diluents and camphor as a volatile material to prepare highly porous compressed tablet. After compression, the tablet will be heated in hot air oven at 500C until a constant weight is obtained to ensure the complete removal of volatilizable component.
d)Disintegrant addition: In this method superdisintegrant 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.
Methods of Collection of Data:
Various fast dissolving tablet formulation of Olanzapine 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 excipient 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 buffer in USP dissolution test apparatus ( Campbell, TDR-08L) using paddle stirrer at 50 rpm.
  1. Short term stability :-
The promosing fast dissolving tablet of Olanzapine will be stored at temperature of 40±20C 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. Sharma D,Kumar D.Fast disintegrating tablets:A new Era in novel drug delivery system and new market opportunities. J Drug Therapeutics 2012;2(3):74-86.
  2. Sayeed A, Mohiuddin M. Mouth dissolving tablets:An overview. Int J Res Pharm Biomed Sci2011;2(3):959-68.
  3. Parashar B, Mayura B, Yadav V, Sharma L. Fast dissolving tablet: An overview. Int Pharm Sci 2012;2(2). 7-16.
  4. SrivastavS,BalaR,JoshiB,RanaA. Mouth dissolving tablets:A Future Compaction. Int Res J Pharm 2012;3(8):98-109.
  5. [updated 2012December 01; cited 2012 Dec 3]. Available from:
  6. NagendrakumarD, Para MS,Design of fast dissolving Graniserton HCL tablets using novel co-processed superdisintegrants.J.Biosci.Tech.2009;1(1):8-14
  7. Jain CP,Naruka PS,Formulation and evalution of fast dissolving tablets of valsartan.Int.J. Pharm.& Pharm Sci.2009;1(1):219-26
  8. Gudas G, Manasa B, Rajesham VV, Kiran S, Prasanna Kumari J. Formulation and evaluation of fast dissolving tablets of chlorpromazine HCL. J Pharm Sci Tech 2010;2(1):99-102.
  9. Jain SK, Shukla M,Shrivastava V. Development and in vitroevaluation of ibuprofen mouth dissolving tablets using solid dispersion technique. Chem Pharm Bull 2010;58(8):1037-42.
  10. Gohil DY, Savaliya RP, Desai SD, Patel DJ. Formulation and characterization of bambuterol hydrochloride fast dissolving tablet using various superdisintegrants. Int J Pharm Sci Res 2011;2(1):84-9.
  11. Manjunatha KM, Desai PD. Design andin-vitroevaluation of mouth dissolving tablets of olanzapine. Asian J Pharm 2011;5(2):107-13.
  12. LakshmiPK,SreekanthJ,Sridharan A. Formulation development of fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit®Epo and optimization through Taguchi orthogonal experimental design. Asian J Pharm 2011;5(2):84-92.
  13. VishwakarmaD,Patel K,PatelN. Formulation and evalution of metoprolol tartrate fast dissolving tablet. American J pharm Tech Res 2012;2(4):412-23.

9 / Signature of the Candidate
10. / Remark of the Guide
11. / 11.1 Guide / Mr.K.Prakash ReddyM.Pharm.
Asst.prof.
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. D. Nagendrakumar M.Pharm.Ph.D.
Department of Pharmaceutics,
SVET’s College of Pharmacy
Humnabad-585330.

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