Rajiv Gandhi University of Health Science, Karnataka s1

FORMULATION AND EVALUATION OF CHLORDIAZEPOXIDE ORODISPERSIBLE TABLETS

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

By

S.MYTHRI

Under the guidance of

Dr. S.S.BUSHETTI M.Pharm, Ph.D

DEPARTMENT OF INDUSTRIAL PHARMACY

H.K.E.S’s COLLEGE OF PHARMACY

GULBARGA-585105

2010-11

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, KARNATAKA

BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate
(In block letters) / S.MYTHRI
Permanent address / PRIYADARSHINI APARTMENT ,FLAT NO:1-10-10,HNO:302,ASHOK NAGAR,SRTEET NO.8,HYDERABAD
2. / Name of the institution / H.K.E.SOCIETY’S COLLEGE OF PHARMACY
SEDAM ROAD,
GULBARGA-585105.
3. / Course of study and subjects / M.PHARM
(INDUSTRIAL PHARMACY)
4. / Date of admission to the course / 17-6-2010
5. / Title of the topic / FORMULATION AND EVALUATION OF CHLORDIAZEPOXIDE ORODISPERSIBLE TABLETS
6 / Brief resume of the intended work
6.1 / Need for the study:
The concept of Fast Dissolving Drug Delivery System emerged from the desire to provide patient with conventional mean of taking their medication. Difficulty in swallowing (Dysphasia) is a common problem of all age groups, especially elderly and pediatrics because of physiological changes associated with these groups of patients. Solid dosage forms that can be disintegrated, dissolved, or suspended by saliva in the mouth resulting in easy swallowing can provide significant benefits to the pediatric and geriatric population, as well as other patients who prefer the convenience of easily swallowable dosage forms.1 Bioavailability of drug from this delivery system is significantly greater than conventional tablet2. The fast dissolving tablet is an important and alternative to liquid dosage form and ideal for unfavorable conditions of administration where water is not available3.
Anxiety is an emotional state, unpleasant in nature associated with uneasiness, discomfort and concern or fear about some defined or undefined future threat. Some degree of anxiety is a part of normal life; treatment is needed when it is disproportionate to the situation and excessive4. Chlordiazepoxide5 is 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzoddiazepine 4-oxide, a first benzodiazepine to be used clinically; Oral absorption is slow and produces a smooth long lasting effect preferred in chronic anxiety states. So, in order to treat the anxiety immediately and to deliver Chlordiazepoxide more efficiently, we are preparing Chlordiazepoxide Oro-dispersible tablets.
6.2 / Review of Literature
Literature survey was carried out by referring various scientific journals and with the facility of internet and helinet, literature review shows that no work has been published on the orodispersible tablets of chlordiazepoxide. Some of the published reports of similar work for various medicinal agents are:
·  Corveleyn S et al6 have worked on Formulation and Production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug. The prepared tablets were evaluated for mechanical strength, porosity, disintegration time, in-vitro dissolution and residual moisture. From their study they concluded that the addition of PEG6000 (1%w/w) resulted in an increase of drug release as 93.3% within 10min and decrease in the strength of the tablet.
·  Ahemed IS et al7 have worked on in-vitro and in-vivo evaluation of fast disintegrating lyophilised dry emulsion tablets containing griseofulvin. From their study they concluded that the poorly soluble drug show an increase bioavailabilty when in corporeted in O/W emulsions.
·  Shirsand SB et al8 have designed fast disintegrating tablet of Prochlorperazine Maleate were prepared by direct compression method. In this method mucilage of Plantago Ovata and Crospovidone were used as superdisintegrants (2-8%w/w) along with microcrystalline cellulose (20-60%w/w) and directly compressible Mannitol to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time and in vitro dispersion time. The results obtained from the Plantago Ovata mucilage are comparable and even slightly better than those of Crospovidone.
·  Areefulla HS et al9 have designed orodispersible tablet of Itopride Hydrochloride were designed with a view to enhance patient compliance by sublimation method with using Crospovidone (2-10%) as super-disintegrant along with directly compressible Mannitol to enhance mouth feel. The prepared formulations were evaluated for hardness, friability, drug content uniformity, wetting time and in vitro dispersion time. From their study they concluded that formulation prepared by sublimation method, emerged as the overall best formulation (t25%=2.9min) compared to the commercial formulation (t50%>30min) i.e., it shows 10 times faster drug release in pH 6.8 phosphate buffer.
·  Yadav R et al10 worked on formulation and in vitro evaluation of Orodispersible dosage form of Stavudine, prepared by direct compression method. They use sugar and superdisintegrants i.e. crosscarmellose calcium, sodium starch glycolate and Crospovidone. The tablet where evaluated for drug content, content uniformity, weight variation, hardness, friability, water absorption ratio, in-vitro disintegration time and in-vitro dissolution study. From their study they concluded that orodispersible dosage form is an alternative to conventional tablets showing enhanced dissolution and hence better patient compliance and effective therapy.
·  Nagendrakumar D et al11 have prepared fast dissolving tablets of Granisetron Hydrochloride by direct compression method. By using a combination of super-disintegrants i.e., sodium starch glycolate-Crospovidone, sodium starch glycolate-croscarmelose sodium and sodium starch glycolate-L-hydroxy Propyl cellulose were used along with directly compressible Mannitol to enhance mouth feel. From their study they stated that short-term stability on the formulation indicated that there were no significant changes in drug content and in vitro dispersion time.
·  Rao NGR et al12 have Prepared Fast Dissolving Tablet of poorly soluble Carbamazepine by the direct-compression techniques with b-Cyclodextrin complexes using Superdisintegrants like Indion-414, Croscarmellose sodium, Crospovidone and sodium starch glycolate. The prepared tablets were evaluated for hardness, friability, drug content, weight variation, disintegrating time, wetting time, in vitro dissolution studies. From their study they concluded that the fast dissolving tablets of the poorly soluble drug, Carbamazepine, with superdisintegrants showing enhanced dissolution and hence, better patient compliance.
·  Patel HA et al13 have prepared Fast dissolving tablets of domperidone using croscarmellose sodium, Crospovidone , sodium starch glycolate as superdisintegrants by direct compression and wet granulation method. The prepared tablets are evaluated for precompression and postcompression parameters and in vitro dissolution dissolution studies. From their study they concluded that Direct compression method can be considered as an important method for the formulation of fast dissolving tablets of Domperidone compare to wet granulation method.
·  Mohanchandran PS et14 al worked on rapid disintegrating oral tablets of Amlodipine besylate by direct compression method using different superdisintegrants. From their study they concluded that combination of super disintegrants were found to be better in formulation of fast dissolving tablet of amlodipine besylate rather than using alone.
·  Prameelarani A et15 al have designed fast disintegrating tablets of Metforminhydrochloride tablets with isphagula husk, naturalsuperdisintegrant and crosspovidone synthetic super disintegrant.The prepared tablets were evaluated for hardness, tensile strength, drug content and friability. from their study they concluded that rapidly disintegrating tablets with proper hardness,rapid disintegration in oralcavity with enhanced dissolution rate can be made using natural and synthetic super disintegrants.
6.3 / Objectives of the study
In the proposed research work we are planning to prepare chlordiazepoxide orodispersible tablets with the following objectives.
1.  Chlordiazetoxide orodispersible tablets will be prepared using some superdisintegrants in varying concentrations by direct compression method.
2.  The prepared orodispersible tablets will be evaluated for various parameters like hardness, Friability, Weight variation, In-vitro dispersion, Drug content uniformity, In-vitro drug release.
3.  Orodispersible tablets after placing on the tongue readily disperses in saliva and the drug is available in solution/suspension form for the immediate absorption and resulting in rapid onset of action.
4.  Though the dissolution/drug release from orodispersible tablet is similar/in parallel to the liquid dosage forms, Stability wise orodispersible tablets are more stable than liquid dosage forms.
5.  Orodispersible tablets disperse readily in presence of saliva and there is no difficulty in swallowing though initially it is a solid dosage forms.
6.  An Orodispersible tablet does not require water for their administrations unlike other solid dosage forms.
7.  With all the above mentioned advantages, we can say orodispersible tablets are patient friendly dosage forms and hence patient compliance can be improved.
7. / Materials and Methods
7.1 / Source of Data:
·  Internet facility
·  www.rguhs.ac.in (helinet facility of our affiliating university RGUHS Bangalore.)
·  Gulbarga University Library, Gulbarga.
·  International pharmaceutical Abstract.
7.2 / Materials
Drug: Chlordiazepoxide.
Formulation additives:
Superdisintegrants: - Crosscarmellose, Crospovidone, Sodium
starch glycolate etc.
Glidants: - Talc, silica, mg stearate, etc,
Lubricant: - Stearic acid, Mg stearate , Ca stearate etc
Antiadherants: - Talc, Starch etc
Disintegrants: - Starch, cellulose etc
Sweetener: - Lactose, Sucrose, Mannitol, Sorbitol etc,
Flavor:-vanilla, fruits, berries, butterscotch16.
Equipments:-
·  Tablet rotary compression machine
·  Tablet hardness tester (Monsanto type)
·  Tablet fribilator( Electrolab make)
·  Tablet dissolution test apparatus-II(electrolab make)
·  UV-visible spectrophotometer (Shimadzu 1700),
·  PH-meter (Elico LI 122),
·  Shimadzu digital balance(0.1mg).
Preparation of Chlordiazetoxide tablet:-
In the present study Chlordiazetoxide orodispersible tablets will be prepared using varying concentrations of superdisintegrants by direct compression method17.
The prepared Orodispersible tablets will be evaluated for various parameters18 like:
1.  Mechanical strength/hardness,
2.  Friability,
3.  Weight variation,
4.  In-Vitro Dispersion,
5.  Drug Content uniformity,
6.  In-Vitro Drug release.
7.3 / Does the study require any investigation or intervention 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 have been obtained from your institution in case of 8.4?
……….………………….Not applicable………………………………..
8.0 / List of References
1.  Yadav IK, Jaiswal D, Sing HP, Chandra D, Jain DA. Formulation Evaluation and Optimization of fast Dissolving Tablets containing Nimesulide Micropellets. Int J ChemTech 2009; 1(4):910-4.
2.  Deshmukh SS, Potnis VV, Mahaparale PR, Kasture PV, Gharge VS et al. Development and Evaluation of Ziprasidone Hydrochloride Fast Disintegrating/Dissolving Tablets using Complexation Techniques. Ind J Pharm educ 2009; 43(3):300-307.
3.  Godge RK, Kendre PN, Giri MA, Syed MZ, Syed NL et al. Formulation and In-Vitro Evaluation of Fast Dissolving/Disintegrating tablets of Tizanidine Hydrochloride. Research J Pharma Dosage Form and Tech 2009; 1(1):55-8.
4.  Tripathi K.D. Essentials of medical pharmacology, 6th edition, Japee brothers medical Publishers (P) Ltd 2008:449-50.
5.  Indian pharmacopoeia commission Central Indian Pharmacopoeia Laboratory Govt of India,Ministry of Health and Family Welfare Sector23,RajnagarIndian Ghaziabad. 2007 ;(2):905.
6.  Corveleyn S, Remon JP. Formulation and Production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug. Int J Pharm 1997; 152:215-25.
7.  Ahemed IS, Aboul-Einien MH. IN-vitro and In-vivo evaluation of a fast disintegrating lyophilized dry emulsion tablets containing griseofulvin. European J Pharma Sci 2007; 32: 58-68.
8.  Shirsand SB, Sarasija S, Para MS, Swamy PV, Nagendra KD. Plantago Ovata Mucilage in the Design of Fast Disintegrating Tablets. Indian J Pharm sci 2009; 41-4.
9.  Areefulla HS, Mujaheed A, Raheem MA, Ayesha S, Bilguese F et al. Orodissolving tablets of Itopride Hydrochloride prepared by sublimation technique. Indian J Pharm sci 2009; 71(2):168.
10.  Yadav R, Gupta RN, Yadav C. Formulation and In-Vitro evaluation of Orodispersible Dosage form of Stavudine. Indian J Pharm sci 2009; 71(2): 163-4.
11.  Nagendrakumar D, Raju SA, Shirsand SB, Para MS, Rampure MV et al. Fast dissolving Tablets of Granisetron Hydrochloride using disintegrant blends for improved Efficacy.Indian J Pharm sci 2009; 71(2):188.
12.  Rao NGR, Patel T, Gandhi S. Development and evaluation of Carbamazepine Fast Dissolving Tablets Prepared with a complex by direct compression technique. Asian J Pharm 2009; 3(2):97-103.
13.  Patel H.A, Patel JK, Patel KN, Patel R.R. Formulation and In-vitro evaluation of Fast dissolving tablets of Domperidone. Int J Pharm Sci 2010;2(1):470-476.
14.  Mohanchandran P.S, Krishnamohan P.R, Saju F, Bini KB et al .Formulation and Evaluation of mouth dispersible Tablets of Amlodipine Besylate.
15.  PrameelaRani A, Archana N, Shivateja P, et al . Formulation and Evaluation of Orodispersible Metformin tablets. Int J Appl Pharma 2010;2(3):15-21.
16.  Aulton ME. Pharmaceutics:the science of dosage form design,2ndedition, Churchill livingstone 2002:405.
17.  Lachman L, Lieberman H.A, Kanig J.L.The Theory and Practice of Industrial Pharmacy,3rdedition,Varghese publishing house 1987:318-19.
18.  Ganeshkumar G, Manasa B, Senthilkumaran K, Rajesham V.V, et al. The Effect of Superdisintegrants on the Dissolution of Promethazine.HCl Fast Dissolving Tablets.International J Pharm sci Nan Tech2010;3(4):867-71.
9. / Signatures of candidate /
S.MYTHRI
10. / Remarks of Guide / With the development of Chlordiazepoxide orodispersible tablets,we can deliver Chlordiazepoxide with no difficulty in swallowing and hence we can improve the patient compliance and the proposed work neither published nor reported any where.
So,recommended for registration.
11. / Name and designation of
(in block letters)
11.1 Guide / Dr. S.S. BUSHETTI. M.PHARM., Ph.D.
PROFESSOR
DEPT.OF INDUSTRIAL PHARMACY
H.K.E.S COLLEGE OF PHARMACY,
GULBARGA-585105
11.2 Signature
11.3 Co-guide / S.B. SHIRSAND. M.PHARM., (Ph.D.)
ASST. PROFESSOR
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S COLLEGE OF PHARMACY,
GULBARGA-585105
11.4 Signature
12. / 12.1 Remarks of Chairman and Principal
12.2 Signature

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