“FORMULATION AND EVALUATION OF TASTE MASKED NICLOSAMIDE SOLID DISPERSION AS CHEWABLE TABLET”

MASTER OF PHARMACY DISSERTATION PROTOCOL

Submitted to

Rajiv Gandhi University of Health Sciences

Bangalore, Karnataka

By

MANJUSHA A

Under the Guidance

OF

Dr. Harish N. MM.Pharm.PhD

DEPARTMENT OF INDUSTRIAL PHARMACY

SRINIVAS COLLEGE OF PHARMACY,

VALACHIL, MANGALORE-574143.

2011 – 2013

Rajiv Gandhi University of Health Sciences

Bangalore, Karnataka

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name and Address of the candidate / Manjusha A
Srinivas College of Pharmacy,
Valachil, Mangalore-574143
2. / Name of the Institution / Srinivas College of Pharmacy,
Valachil, Mangalore-574143
3. / Course of study and subject / Master of Pharmacy
(Department of of Industrial Pharmacy)
4. / Date of admission to course / 31st october 2011
5. / Title of the topic / “FORMULATION AND EVALUATION OF TASTE MASKED NICLOSAMIDE SOLID DISPERSION AS CHEWABLE TABLET”
6. Brief resume of the intended work
6.1 Need of the study:

Administration of drug through oral route is the most common and easiest way to administer a drug. Fast disintegrating,sustained release,sublingual,chewable, andcolon targeted tablets are some of the oral tablets.Among these chewable tablets improves the compliance in children and geriatric patience.It is a challenge in children who have not yet learned to swallow tablets.

Chewable tablets disintegrate slowly when chewed or allowed to dissolve in the mouth for local action. Chewable tablets are especially useful in tablet formulations for children and are commonly employed in the preparation of multiple vitamin tablets.
Advantages of chewable tablets
  • Reduction of transportation cost
  • Over liquids dosage form chewable tablets have many advantages like portability,stability etc
  • Lack of precision can be avoided
  • Over the other solid dosage form it has higher patient compliance1
Niclosamide is an effective anthelmintic drug for the treatment of intestinal cestode infections in human. It is also used as treating molluscide for treating water in the control of schistosomiasis
It is available in 4 types of salt form. Ethanolamine,niclosamine ,piperazine, and niclosaminemonohydrate salt etc.It is yellowish grey odourless crystalline solid, which melt between 224-229oC.The ethanolamine salt form is yellow solid melting at 1910C.
Solubility: is not very water soluble, sparingly soluble in ether,ethanol,and chloroform but soluble in acetone.The ethanolamine salt dissolves in distilled water.
Stability;-in tablet form niclosamide undergoes biodegradation in moist environment.But itis stable in aqueous solution for several months. Ethanolamine salt is stable to heat. Hydrolyzed by acid or alkali and stable at aquatic environment2
The drug appears to act by inhibiting oxidative phosphorylation in mitochondria and interfering with the anaerobic generation of ATP by the tapeworm.Injured tapeworms by niclosamide gets partially digested in the intestine.3
Solid dispersion is one of the means to mask the taste of the drug.It is a dispersion of one or more ingredients in an inert carrier matrix or at solid state. Various approaches of solid dispersion are melting method, solventmethod, melting solvent method. The masked taste can be tested by panel testing. It is a psychophysical rating of the gustatory stimuli.4
6.2 - Review of Literature:
  1. Swati Jagdale, Mahesh Gattani, Dhaval Bhavsar, Bhanudas Kuchekar, Aniruddha Chabukswar5 formulated levamisole chewable tablet by wet granulation method using surfactants SLS,polymer PVP,exciepients like lactose, mannitol,disintegrating agent like SSG,starch,magnesium stearate,stearic acid etc. Granules are evaluated for angle of repose, Hausner’s ratio,percentage compressibility, and sieve analysis.Tablets were evaluated for friability, hardness,disintegration, dispersion, dessolution and drug content test.From this they observed that tablet containing lactose and SSG of 1.6% concentration gives the best levamisole chewable tablet with minimum disintegration time,hardness,pleasant taste and meet the IP requirements.
  2. Sukhbir. L. Khokra, Bharat Parashar, Hitesh kumar D, Rahul P, Abhishek C6. formulated chewable tablet containingAlbendazole by different techniques,like non-aqueous granulation, aqueous granulation,direct compression etc.The evaluation of tablet was done by, Carr’s index, tapped density,visual identity,odour,taste,surface texture,weight uniformity,hardness, friability, disintegration, content uniformity test, invitro dissolution etc any deviation from which leads to under medication or overmedication.Using Monsanto’s hardness test all the tablet showed good hardness. The friability was 0.2% for all the blends found to be satisfactory.Assay volume was within the range of 90-110%.They found that all the parameters were within the specifications.The dissolution profile of batches of tablet prepared by direct compression method has shown better results compared to tablet prepared by other methods.
  3. Kathiresan K , Vijin P, Moorthi C, Manavalan R7 formulated and evaluated loratidine chewable tablet by wet granulation method.The prepared blend analyzed for flow properties such as Carr’s index, Hausner’s ratio, angle of repose etc.The outcome of these parameter indicated good flow properties.Physical characteristics like diameter,thickness,wt variation,hardness,fraiability were done and showed better physical characteristics.
  4. Pasupathi A, Haresh A. Patel, R. Margret Chandira, D. Bhowmik, Jaykar B8 formulated lamotrigine antiepileptic chewable tablet by direct compression and wet granulation method using LME01 as a drug and crosspovidone XL10 as a disintegrating agent.Here different grades of mannitol (pearlitol 160C, pearlitol SD200, pearlitol 500DC) used as a diluents. PVP K30 acts as binder.Furthermore,impact of different punches and superdisintegrants were carried out. The sweetening agent used is saccharine and aspartame and flavor was black current.They found that crosspovidone is better disintegrating than SSG.In direct compression method flowproperty,hardness,cracking problems etc were found. The evaluation parameter of wet granulation was better than direct compression.They found wet granulation is better using pearlitol 500DC grade mannitol.
  5. Shaik Harun Rasheed, Sandhya Vani P, Silpa Rani Gajavalli9 formulated and evaluated mebendazole chewable tablet by wet granulation method using SLS, PVP, lactose, mannitol, SSG,Magnesium stearate, stearic acid, starch etc.Evaluation of granules were done byangle of repose, Carr’s compressibility index, Hausner’s ratio etc.Tablets are evaluated by weight variation technique,hardness,assay of drug content, disintegration, etc.They found that after adding lubricant showed decrease in angle of repose. LM4 batch shows maximum change of angle of repose after adding lubricant.Hausner’s value is less than 1.25% indicates good flowability,% weight variation was within the limits.Hardness value was in the range of 2.6-4.2. Maximum hardness obtained for batch LM2.Lactose and SSG 1.6% show minimum disintegration time than formulation containing mannitol formulation.
  6. Pankaj P. Amrutkar, Sanjay B. Patil, Abhijeet N10 designed and evaluated chewable dispersible tablet of lamotrigene by meltgranulation method.The effect of different concentration of disintegrant on disintegration and effect of taste masking agent precirol ATO 05 was studied.The tablets are subjected for various preformulation studies and various tests like taste evaluation, mouth feel, wetting time,disintegration,dispersion, invitro dissolution,etc.From the taste evaluation they found that the F6 formulation did not shows any bitter taste.The precirol in 1:2 proportions with the drug gives the better taste masking effect.The wetting time was rapid in case of crosspovidone followed by SSG. All parameters of the tablets were found to be within the limits. They found that these tablets have good acceptable taste and can be commercialized.
6.3 - Objectives of the study
The present research study is planed with the following objectives.
1)To formulate niclosamide solid dispersion for taste masking using different techniques.
2)To formulate and evaluate niclosamide chewable tablet by compression method.
3)To evaluate the formulations with respect to various physical parameters (Solid dispersion & Chewable tablet).
4)To evaluate the formulations with respect to content uniformity, in vitro release studies, etc.
5)To perform the stability studies on promised formulations.
7 - Materials and Methods:
  1. Drug : Niclosamide anthelmintic drug
  2. Excipients : Polymers – PVP, SSG
  3. Diluents-mannitol,lactose,starch
  4. Binding Agent –PVP K30
  5. Wetting agent-SLS
  6. Lubricants - Magnesium stearate,Stearic acid
  7. Taste masking agent- β cyclodextrins, PEG.
  8. Flavouring agent- Raspberry flavour
9. Sweetening agent- Sodium saccharin
  1. Suitable punching tools.
  2. Tablet compression machine
Methods:
  1. Niclosamide solid dispersion can be done by any one of the technique
  2. Niclosamide Chewable tablet can be prepared by compression method
  3. Panel testing:It is a psychophysical rating of the gustatory stimuli; in this method a group of about 5-10 volunteers are trained for taste evaluation by using reference solutions ranging in taste from tasteless to very bitter.Numerical values are then assigned to these levels of bitterness. Subsequently, test solution is tasted and rated on the same scale to assess its bitterness
7.1 - Source of Data: Review of literature from
a)Journals
  • Research article on formulation and evaluation of chewable tablet
  • International Journal of Pharmacy
  • Research Journal of Pharmaceutical biological and chemical science
  • Pharma research Journal of epileptic drug
  • International Journal of Pharmaworld research
  • Islamic university Journal
  • International Journal of Pharmacy and Pharmascience
  • The International Journal of drug delivery
b)Internet Browsing.
c)Laboratory Based Studies
7.2 – Method of Collection of Data:
  1. An Overview of anthelmintic chewable tablets
  1. Formulation of chewable tablets
  1. Evaluation of formulated anthelmintic chewable tablet as follows:
Drug-Excipient interaction studies by FTIR
Preformulation parameters – Angle of repose, Carr’s compressibility index, Particle size analysis, Hausner’s ratio, Tapped density
Hardness
Friability
Weight variation
Drug content
Wetting time and Water absorption ratio
Uniformity of dispersion
In-vitro disintegration time
In vitro drug release study: USP II dissolution by paddle method
Stability studies as per ICH guidelines
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 work
7.4 - Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
8-List of References
  1. AbdelNaser Zaid, Abeer OAbughosh, Waleed M. Sweileh, Samah W. Al-jabi, Nidal A.Jadarat. Chewable tables: is this dosage form well evaluated by palastinian health professionals?The Islamic university journal. 2007 ;15(2):83-94
  1. Yi W. Chang,Teng K Yeh, KeTa.Lin.Wei-cheng chen, Hsien-Tsung Yao, Shih-Jung Lan,
Yu-ShanWu, Hsing-Pang Hsieh, Chi-Min Chen, Chiung-Tong ChenPharmacokinetics of anti SARS-cov agent Niclosamide and its analogue in rats. Journal of food and drug analysis. 2006;14(4)329-33
  1. KD Tripathi, Text book of essential pharmacology. 6th Edn. Jaypee publication. 2008;814
  1. Ahire SB, Banka VH,Gayakwad PD, Pawar SP, A review: taste masking techniques in pharmaceuticals.Int. J. Pharm. Sci. 2011;1645-1657
  1. Swati Jagdale, Mahesh Gattani, Dhaval Bhavsar, Bhanudas Kuchekar, Aniruddha Chabukswar. Formulation and evaluation of chewable tablet of levamisole. Int. J. Res. Pharm. Sci.2010 1(3), 282-289,
  1. Sukhbir. L. Khokra, Bharat parashar, Hitesh kumar D, Rahul P, Abhishek C.Formulation development and evaluation of chewable tablet of Albendazole by different techniques. Int. J. Pharm. Pharm. Sci. 2011;4(1)461-464
  1. Kathiresan K , Vijin P, Moorthi C, Manavalan R. Formulation and evaluation of loratadine chewable tablets. RJPBS.2010;1(4).763-774
  1. A Pasupathi, Haresh A. Patel, Margret Chandira.R, Bhowmik.D, Jaykar.B. Formulation and evaluation of chewable dispersible tablet of anti epileptic drug. T. Ph. Res. 2010;4:74-82
  1. Shaik H. Rasheed, P. Sandhya vani, Silparani Gujavalli, Shahul Hussain SK, Venugopal B, Ravikiran T, Sridevi S, Kishore Yadav S.Formulation and evaluation of chewable tablet of Mebendazole. International quarterly published online research journal. 2011;2(3)1-14
  1. Pankaj P. Amrutkar, Sanjay B. Patil, Abhijeet N. Todarwal1 , Manoj A. Wagh, Parag D. Kothawade, Rajendra K. Surawase. Design and evaluation of taste masked chewable dispersible tablet of lamotrigine by melt granulation.International Journal of Drug Delivery. 2010;183
  1. Santanu Roychowdhury,Atul Tuli, Pawan Sharma, Paras Bedi, M.U.Khan. The Indian pharmacist. Advances in different granulation technique. 2012;10(10)29-37
  1. Halder A, Behera A, S.SI, Biswal. I, Dinda.A .Preparation of loperamide hydrochloride chewable tablet:Methode of validation by HPLC. Int. J. Phar. Pharm. Sci. 2012;4(2)372-376
  1. Manali S. Mulay, Sagariatil, Vidhyadhar H. Bankar, Preeti D. Gaikwad, Sunil P. Pawar. Taste masking by inclusion complexation:A review. IJPRD. 2011;3(7)35-47
  1. Kruthi M, Sandhya Rani A, Srikanth Kumar K.Development and evaluation of taste masked orodispersible tablets of drotaverine Hcl. Int. J. Pharm. Sci.2011; 1. 1-18
  1. Shishu, Kamalpreet, Kapoor V.R.Development of Taste Masked Oral Formulation of Ornidazole. Indian J Pharm Sci. 2010; 72(2): 211–215.
  1. Rakesh K Deore, Kavitha K, Theetha G Tamizhmani. Preparation and evaluation of sustained release matrix tablets of Tramadol Hcl using glyceryl palmitostearate. T. J. Pharm. Res. 2010; 9(3).275-281
  1. Magdy M. Ibrahim, Mohamed EL-Nabarawi, Doaa Ahmed El-Setouhy, Montasir A. Fadlalla. Polymeric Surfactant Based Etodolac Chewable Tablets. AAPS PharmSciTech. 2010; 11(4) 1730–1737.
  1. Aftab Modi, Pralhad Tayade. Enhancement of dissolution profile by solid dispersion technique. AAPS PharmsciTech. 2006;7(3)
9. / Signature of candidate / Manjusha A
10. / Remark of the guide / The above information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance.
11 / Name & Designation of
11.1 Guide / Dr.Harish.N. MM Pharm PhD
Associate Professor
Department of Industrial Pharmacy
Srinivas college of Pharmacy
Valachil, Mangalore
574143
11.2 Signature
11.3 Co-Guide (if any) / ------
11.4 Signature / ------
11.5 Head of the Department / Dr. Harish N. MM.Pharm., Ph.D.
Associate professor
Department of Industrial Pharmacy
Srinivas College of Pharmacy
Valachil, Mangalore
574143
11.6 Signature
12 / 12.1 Remark of the Director / principal / The above mentioned information is correct and I recommend the same for approval.
12.2 Signature / Dr.A.R. Shabaraya
Principle and Director
Srinivas college of pharmacy
Valachil, Mangalore
574143
.
.