Formulation and Evaluation of Orodispersible Tablets Of

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF

CEFPODOXIME.

M. Pharm. Dissertation Protocol Submitted to

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore – 560041

By

Miss. SARIKA S. JADHAV. B.Pharm

Under the Guidance of

Mrs. ASHWINI S. JOSHIM. Pharm

DEPT. OF PHARMACEUTICS

Post Graduate Department of Pharmaceutics

SET’S College of Pharmacy,

S. R. Nagar, Dharwad,

Karnataka – 580002.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE

KARNATAKA

ANNEXURE-II

PROFORMA OF REGISTRATION OF SUBJECT OF DISSERTATION

1 / NAME OF THE CANDIDATE
AND ADDRESS / Miss. JADHAV SARIKA SAMPATRAO.
SONIYA EDUCATION TRUST’S COLLEGE OF PHARMACY,
S. R. NAGAR, DHARWAD 580002.
2 / NAME OF THE INSTITUTION / SONIYA EDUCATION TRUST’S COLLEGE OF PHARMACY, DHARWAD 580002.
3 / COURSE OF THE STUDY AND SUBJECT / MASTER OF PHARMACY IN
PHARMACEUTICS
4 / DATE OF ADMISSION TO THE COURSE / JULY 2013
5 / TITLE OF THE TOPIC:
FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF
CEFPODOXIME.
6.0
7.0
8.0 /

BRIEF RESUME OF THE STUDY :

6.1 NEED FOR THE STUDY:

The oral drug delivery system is widely used in different mode of drug dosing form. In
the Pediatric and Geriatric patients they have difficulty in swallowing the tablet ,so Orodispersible tablet is prefered in these patients.Orodispersible Tablets (ODTs) are solid single-unit dosage forms that are placed in mouth, allowed to disperse/dissolve in the saliva without the need of water and provide a quick onset of action. Some drugs are absorbed from mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form. Orodispersible tablets are readily accepted by children and elderly, who have difficulty in swallowing conventional tablets or capsules.
Orodispersible tablet has several advantages like-
A) Benefit of liquid medication in the form of solid preparation.
B) Pregastric absorption can result in improved bioavailability and as a result of reduced dosage, improved clinical performance through a reduction of unwanted.
C) No need of water to swallow the dosage form, which is highly convenient feature for patients who are travelling and do not have immediate access to water.
D) Good mouth feel property of Orodisperseble Tablets (ODTs) helps to change the psychology of medication as “bitter pill” particularly in pediatric patients.
E) Rapid dissolution of drug and absorption, which may produce rapid onset of action.1
Antibiotics are strong medicines,that they are used to treat bacterial infections, including some that can be life threatning .Some antibiotics are Broad Spectrum. These antibiotics can attack many different type of bacteria. Other antibiotics are more specific and only attack one type of bacteria. Antibiotics can be used to treat some fungal infections, treat infections caused by certain type of parasites. The β lactam also include Cephalosporin antibiotics, which are classified by generation:
1st generation –Gram +ve and gram –ve.
2nd generation – Gram –ve , anaerobic.
3rd generation – Gram +ve , Enterobacteriaceae and 4th generation agents encompass the antimicrobial spectrum of all the third generation agent and have increased stability to hydrolysis by inducible chromosomal β lactamases.2 Cefpodoxime proxetil is the isopropyl oxycarbonylethyl ester of the third generation cephalosporin Cefpodoxime. This orally active prodrug derivative is hydrolyzed by esterases in the intestinal wall and plasma to provide Cefpodoxime . Tablet and powder for the preparation of an oral pediatric administration are available. The oral bioavailability of Cefpodoxime form the proxetil is estimated to be about 50% . Cefpodoxime is abroad spectrum Cephalosporin with useful activity against a relatively wide range of gram negative and gram positive bacteria.
Superdisintegrants are added to a drug formulation to facilitate the break-up or disintegration of tablet into smaller particles that can dissolve/disperse more rapidly than in presence of disintegrants.3
Sublimation method to create sythetic materials is a method where solids are heated at appropiate temperatures and pressure, usually in a near vacuum. In this process the compound if subjected to heating, changes from solid state to gaseous state happens directly without passing through a phase of liquid. Such compounds from the gaseous state gets deposited on the cooler surface in the form of crystals or cake.4 Microparticles are prepared by using Camphor as sublimating agent in this method.
In this work attempt will be done to prepare the Orodispersible tablets by combining both super-disintegrant method and sublimation method so that a better Orodispersible tablet could be achieved.
6.2 REVIEW OF LITERATURE:
Fast dissolving tablets of Valsartan using different superdisintegrants by direct compression method was studied and effect of disintegrant on disintegration behaviour of tablet in artificial saliva with pH 5.8 was evaluated. Wetting time of formulations containing Crosspovidone was least and tablets showed fastest disintegration. The drug release from fast dissolving tablets increased with increasing concentration of superdisintegrants and was found to be highest with formulations containing Crosspovidone.3
Felodipine fast dissolving tablets were prepared using novel co-processed superdisintigrants, containing mannitol, sodium stearyl fumarate, sodium lauryl sulphate, talc, magnesium stearate . In-vitro dispersion time approximately was found to be 17 second.5
The study of thefast dissolving tablets of Promethazine HCl, using various superdisintegrants by direct compression method containing Eudragit E-100, starch, microcrystalline cellulose (Avicel Ph102 and Avicel Ph101), lactose, 5% Crossprovidone (PolyplasdoneXL), Crosscarmellose sodium, Colloidal silicone dioxide, magnesium stearate, talc was done. Promethazine HCl with Eudragit E-100 masked its bitter taste as well as improve its dissolution profile, tablets containing 5% crosspovidone (Polyplasdone XL) gave the highest improvement in disintegration and dissolution rate of Promethazine HCl.6
The study of the effect of various superdisintegrants on tablets of Salbutamol sulphate by employing direct compression method, using various concentration of superdisintegrants like Ac-di-sol, primojel, and polyplasdone R-XL as 2%,3%,4%,5%., shows 100% drug release ,disintegration time of formulation was 25 second because of superdisintegration was found.7
The mouth dissolving tablets of Zopiclone was prepared by direct compression method using combination of super-disintegrsants i.e. Ac-di-sol (Crosscarmellose sodium), Polyplasdone XL-10. Microcrystalline Cellulose Ph 102 was used along with directly compressible dextrose to enhance mouth feel and the disintegration time was found to be in the range of 24-50 second.8
The study was done onorally disintegrating tablets of Sertraline by direct compression using super disintegrants like crosspovidone, crosscarmellose sodium and sodium starch glycolate, lactose, microcrystalline cellulose, the disintegration time was found to be17-32 second.9
Fast dissolving tablets of Aceclofenac were prepared by direct compression method after incorporating superdisintegrants like crosscarmellose sodium, crosspovidone and sodium starch glycolate, microcrystalline cellulose. Tablets containing crosscarmellose sodium showed excellent in vitro dispersion time and drug release as compared to other formulation Thus wetting times of tablets was found to be crosspovidone ≤ crosscarmellose sodium ≤sodium starch glycolate. While dispersion time was found crosscarmellose sodium ≤ sodium starch glycolate ≤ crosspovidone.10
Preparation of fast dissolving tablets of Glipizide by direct compression method with a view to enhance patient compliance was studied withtwo superdisintegrants viz, crosspovidone and crosscarmellose sodium (4%, 5%, 6%) with different binders viz, polyvinyl pyrrolidone (pvp) k-30 and pregelatinized starch (3%) were used. The disintegration time for formulations was found to be 11-21 seconds .11
Fast dissolving tablets of the drug Amitriptyline hydrochloride using superdisintegrants such as Crosscarmellose sodium (Ac‐Di‐Sol), Sodium starch glycolate (Explotab) and Crosspovidone, microcrystalline cellulose, by direct compression technique was done. Crosspovidone was found to be better suited for the formulation of mouth dissolving tablet of Amitriptyline hydrochloride compared to other superdisintegrarnts used in the study. Tablet containing Crosspovidone having low dispersion time as compare to other superdisintegrants. The dispersion time increases as the concentration of superdisintegrants increases. The in vitro disintegration time of the tablets was found to be less than 60 second.12
Compressed tablets of a water-soluble material was prepared by using mannitol and was foud that it did not rapidly dissolve in water since it wass difficult for water to penetrate into the tablets due to their low porosity. To increase the porosity of the tablets which are prepared by direct compression using mannitol, they developed a novel method whereby camphor, a subliming material, is removed by sublimation from compressed tablets prepared using a mixture of mannitol and camphor. A high porosity was achieved due to the formation of many pores where camphor particles previously existed in the compressed mannitol tablets prior to sublimation of the camphor. These compressed tablets which have high porosity (approximately 30%) rapidly dissolved within 15 s in saliva in the mouth.13
Preparation of Aceclofenacfast dissolving tablets by sublimation method was employing with crosspovidone and sodium starch glycolate and as super-disintegratant in different ratio along with up to 30% w/w of camphor as a sublimating agent. A total of 6 formulation and control formulation f0 (with out super-disintegrant) were designed.14
By using combined approach of sublimating agent and super-disintegrant an optimized mouth dissolving tabtet formulation of Venlafaxine hydrochloride was formulated. It appeared that use of super-disintegrant in higher concentration and camphor in lower concentration results in faster disintegration of the tablets with low friability camphor , used as sublimating agent, increased porosity of tablets was due to which penetration of water took place at high rate and this leads to faster disintegrationof the tablets.15
6.3 OBJECTIVE OF THE STUDY:
1)The main objective of the present study is to formulate orally disintegrating tablets to achieve better dissolution rate and further improving the bioavailability of the drug.
2)To check drug compatibility with superdisintegrants like crosscarmellose, L-HPC (low substituted hydroxyl propyl cellulose), sodium starch glycolate etc and Sublimation by suitable method.
3) To develop Orodispersible Tablet dosage form.
4) To study in-vitro drug release profile.
5) To evalute the tablets for Hardness, Friability and Weight uniformity.
6) To evalute the physical properties of powder blend of tablet batches such as Angle
of repose, Bulk density and Compressibility index.
MATERIALS AND METHODS:
7.1SOURCE OF DATA:
● Reference Books.
●
● Web resources.
● Indian journal of pharmaceutical sciences.
● AAPS Pharma Sci Tech.
● International journal of Pharmaceutical research.
● International journal of pharmacy and pharmaceutical science.
7.2METHOD OF COLLECTION OF DATA:
The data was collected by referring various standard reference books, journals & other sources like research literature data bases such as science direct etc.
A.MATERIALS :

• Antibiotic – Cefpodoxime.
• Superdisitegrants- crossprovidone, crosscarmellose sodium, L-HPC (Low substituted hydroxy propyl cellulose), Sodium starch glycolate along with various excipients are used in formulation of Orodisperseble Tablets.
• Sublimation-Camphor, Mannitol this are excipients used in formulation of Orodisperseble Tablets.

B. METHOD :
The active agent and excipients will be formulated into tablet by combining both Super-disintegrant and Sublimation technique.
C. EVALUATION STUDIES:

1. Precompression studies-

Bulk density
Tapped density
Bulkiness
Angle of repose
Compressibility and Hausner’s ratio

1. Post compression studies-

Hardness
Friability
Weight variation
Water uptake study
Disintegrating test
Drug content
D. IN VITRO DISSOLUTION STUDY:
In vitro dissolution studies will be carried out by USP XXIII dissolution test apparatus at 50 rpm. Using suitable dissolution medium which is maintained at 37±0.50C and will be analysed by UV spectrophotometer .
7.3Does the study require any investigation or investigation to be conducted on patient or other humans or animals? If so please describe briefly.
- No -
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
- Not applicable -
LIST OF REFERENCES:

1. Manivannan R. Oral disintegrating tablets a future compaction. Int J Pharm Res Dev 2009;1(10):1-10.
2. Brunton LL, Lazo JS, Parkar KL. Goodman and Gilman. The Pharmacological basis of therapeutics.11thed. New York: McGRAW-HILL Medical publishing Division.
3. Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of Valsartan. Int J Pharm Pharm Sci 2009;1(1):219-226.
4. Rangari V. Pharmacognosy and phytochemistry. General method of extraction and purification. Career Publication. 2007;1(1):141.
5. Raghavendra Rao N. G, Kulkarni U. Formulation and design of fast dissolving tablets of Felodipine using novel co-processed superdisintegrants. Int J Pharm Res Dev 2010;2(9):113-121.
6. Mahamuni SB, Shahi SR, Shinde NV, Agrawal GR. Formulation and evaluation of fast dissolving tablets of Promethazine HCl with masked bitter taste. Int J Pharm Res Dev 2009;7:1-18.
7. Khinchi MP, Gupta MK, Bhandari A, Agrawal D, Sharma N, Gupta SK. Effect of various superdisintegrants on drug release of orally disintegrating tablet. Int J Pharm Res Dev 2010;2(5):1-8.
8. Umalkar DG, Rathinaraj BS, Bangale GS, Shinde GV, Kumaraswamy D, Rajveer C, Rajesh KS. Design and evaluation of mouth dissolving tablet of Zopiclone using different superdisintegrants. J Pharm Sci Res 2010;2(1):527-533.
9. Kakade SM, Mannur VS, Kardi RV, Ramani KB, Dhada AA. Formulation and evaluation of orally disintegrating tablets of Sertraline. Int J Pharm Res Dev 2010;1(12):1-7.
10. Wagh MP, Yewale CP, Zate SU, Kothawade PI, Mahale GH. Formulation and evaluation of fast dispersible tablets of Aceclofenac using different superdisintegrant. Int J Pharm Pharm Sci 2010;2(1):154-157.
11. Patel B, Patel D, Parmar R, Patel C, Serasiya T, Sanja SD. Development and In vitro evaluation of fast dissolving tablets of Glipizide. Int J Pharm Pharm Sci 2009;1(1):145-150.
12. Mohsin AA, Nimbalakr N.E, Sanaullah S, Aejaz A. Formulation and evaluation of mouth dissolving tablets of Amitriptyline Hydrochloride by direct compression technique. Int J Pharm Pharm Sci 2010;2(1):204-210.
13. Kei-ichi Koizumi. New method of preparing high porosity rapidly saliva soluble compressed tablets using mannitol with camphor , a subliming material . Int J Pharm 1997;152:127-131.
14. Kalpesh Gaur, Lalit K.Tyagi, M.L.Kori, C.S.Sharma, R.K.Nema. Formulation and characterization of Fast Disintegrating Tablet of Aceclofenac by using Sublimation Method. Int J Pharma Sci and Drug Res 2011;3(1):19-22.
15. Inayat Bashir Pathan, Prakash Shingare, Pritish Kurumkar. Formulation design and optimization of novel mouth dissolving tablets for Venlafaxine hydrochloride using sublimation technique. J Pharm Res 2013;6:593-598.

9. / SIGNATURE OF THE STUDENT
10. / REMARK OF THE GUIDE
The above mentioned 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. / 11.1 NAME AND DESIGNATION OF THE GUIDE
11.2 SIGNATURE / Mrs. ASHWINI S. JOSHI. M. Pharm,
LECTURER
DEPARTMENT OF PHARMACEUTICS,
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
11.3 NAME AND DESIGNATION OF CO-GUIDE
11.4 SIGNATURE / ------
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE / Prof. A.M.GODBOLE. M. Pharm, Ph.D.,
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS,
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
12. / 12.1 REMARK OF THE PRINCIPAL
12.2 SIGNATURE / The above mentioned information is correct
and I recommend the same for approval.
Dr. V. H. Kulkarni. M. Pharm, Ph.D.,
PROFESSOR & PRINCIPAL,
SET’s College of Pharmacy,
S.R.NAGAR, DHARWAD- 580002.

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