Formulation and Evaluation of Orodispersible Tablets of Anantihypertensive Drug

“FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF ANANTIHYPERTENSIVE DRUG”

M. Pharm. Dissertation Protocol Submitted to

RajivGandhiUniversity of Health Sciences, Karnataka

Bangalore – 560041

Mr. SIDANINGAPPA BAGALI.B.Pharm

Under the Guidance of

Dr. M.S.SRINATHM. Pharm.PhD.

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 / Mr. SIDANINGAPPA BAGALI.
SET’s COLLEGE OF PHARMACY,
SANGOLLI RAYANNA NAGAR,
DHARWAD- 580 002.
2 / NAME OF THE INSTITUTION / SET’s COLLEGE OF PHARMACY
DHARWAD
3 / COURSE OF THE STUDY AND SUBJECT / MASTER OF PHARMACY
INPHARMACEUTICS
4 / DATE OF ADMISSION TO THE COURSE / JULY- 2011
5 / TITLE OF THE TOPIC:
“FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OFAN ANTIHYPERTENSIVE DRUG”
6.0
7.0
8.0 /

BRIEF RESUME OF THE STUDY:

6.1NEED FOR THE STUDY:

Oral routes of drug administration have wide acceptance up to 50-60% of total dosage forms. Solid dosage forms are popular because of ease of administration, accurate dosage, pain avoidance and most importantly the patient compliance. The most popular solid dosage forms are being tablets and capsules; one important drawback of this dosage forms for some patients, is the difficulty to swallow. Drinking water plays an important role in the swallowing of oral dosage forms.For these reason, tablets that can rapidly dissolve or disintegrate in the oral cavityhave attracted a great deal of attention. Orodispersible tablets are not only indicated for people who have swallowing difficulties, but also are ideal for active people. Fast dissolving tablets are also called as mouth-dissolving tablets, melt-in mouth tablets, Orodispersible tablets, rapimelts,porous tablets, quick dissolving etc. Fast dissolving tablets are those when put on tongue disintegrate instantaneously releasing the drug which dissolve or disperses in the saliva. The faster the drug goes into solution, quicker the absorption and onset of clinical effect. Some drugs are absorbed from the 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 tablets dosage form. The advantage of mouth dissolving dosage forms are increasingly being recognized in both, industry and academics. Their growing importance was underlined recently when European pharmacopoeia adopted the term “ Orodispersible tablet” as a tablet that to beplaced in the mouth where it disperses rapidly before swallowing.1
Another benefit of Orodispersive tablets, it does not require water or chewing before swallowing. Some Orodispersive tablets aredesigned to dissolve within a few seconds are generally known as true oral disintegrating tablets. OtherOrodispersive tablets containing some agents which will increase the rate of disintegration in the oral cavity(Superdisintegrant) are simply called as oral disintegrating tablets, which may take up to a minute forcomplete disintegration in the mouth.The target of these new oral dissolving/disintegrating dosage forms have generally been pediatric,geriatric, bedridden and developmentally disabled patients and also patients with persistent nausea, whoare in traveling, or who have little or no access to water are also good candidates for Orodispersive tablets.2
United States Food and Drug Administration define orally disintegrating tablets as “A solid dosage form which contain a medicinal substance or active ingredient which disintegrates rapidly within a matter of seconds when placed upon a tongue”.
orally disintegrating tablets as ‘uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed’ and as tablets which should disintegrate within 3 min.3
Characteristics of an ideal orally disintegrating drug delivery system
Orally disintegrating drug delivery system should possess following characteristics:

Utilizes cost effective production method.
Require no water for oral administration.
Dissolve / disperse/ disintegrate in mouth in a matter of seconds.
Have a pleasing mouth feel and taste masking.
Less friable and have sufficient hardness.
Leave minimal or no residue in mouth after administration.
Manufacturing using conventional manufacturing method. 3

Hypertension is avery common disorder, particularly past middle age. It is not for disease in itself, but is an important risk factor for cardiovascular mortality and morbidity. It is be 140 mm Hg systolic and 90 mm Hg diastolic, though risk appears to increase even above 120/80 mm Hg. Antihypertensive drugs, by chronically lowering blood pressure, may reset the barostat to function at a lower level of blood pressure.
6.2REVIEW OF LITERATURE:
Bedi N, etal.,Prepared Mouth dissolving tablets of oxcarbazepine. In thisstudy, the mouth dissolving tablets were prepared using two different technologies, direct compression method and solid dispersion technology. Tablets produced by direct compression method contain crospovidone as a superdisintegrant and aspartame as a sweetener. Solid dispersions of oxcarbazepine with polyvinylpyrrolidone K-30 and polyethylene glycol 6000 in different weight ratios were prepared with a view to increase its water solubility. Oxcarbazepine solid dispersions with polyvinylpyrrolidone K-30 in 1:2 ratios of drug: carrier showed maximumdrug release and hence, compressed along with other excipients into mouth dissolving tablet.5
Jain CP,etal., Prepared fast dissolving tablets of valsartan were prepared using different superdisintegrants by direct compression method. Crospovidone was least and tablets showed fastest disintegration. The drug release from FDTs increased with increasing concentration of superdisintegrants and was found to be highest with formulations containing Crospovidone.6
Raghavendrarao N G, etal.,Prepared Fast dissolving tablets of the carbamazepine by wet granulation method, using different concentrations of natural superdisintegrating agent like plantegoovata seed powder and mucilage. Results revealed that it is possible to enhance dissolution rate will lead to improve bioavailability by using wet granulation technique using different concentrations of both seed powder and mucilage of plantego ovate as superdisintegrants. Overall results indicates that formulation SM5 that contain 25 % natural superdisintegrant like mucilageplantegoovataexhibited faster drug dissolution will lead to improve bioavailability, effective therapy, improve patient compliance, and satisfies all the criteria as fast dissolving tablet.7
Wagh MP, etal.,Prepared Fast dispersible tablets of aceclofenac usingdifferent superdisintegrantThe dissolutionparameters were consistent with dispersion times of
croscarmellose sodium and sodium starch glycolatecontaining tablets, while not consistent withcrospovidone. After study of nine formulations F3 shows short dispersion time with maximum drugrelease in 30 min.8
Kakade SM,etal., Prepared Orally disintegrating tablets of Sertraline. Orally disintegrating tablets prepared by direct compression and using super disintegrants like
crospovidone, croscarmellose sodium and sodium starch glycolatecrospovidone emerged as the best formulation and showed maximum dissolution rate with 98.49% drugrelease in 15 min.9
Arya A, etal.,preparedMouth dissolving tablets of Ranitidine HclThe tablets were prepared by using sublimation method using ammonoiumbicarbonate as sublimating agent. The other tablets prepared by using sodium starch glycolate and cross carmellose sodium as superdisintegrant. Itwas concluded that the tablets prepared by super disintegrant addition have better disintegrating properties and releaseprofile when compared to the tablets prepared by sublimation method.10
UmalkarDG,etal., Prepared Mouth dissolving tablet of Zopiclone usingdifferent superdisintegrantsA combination of super-disintegrantsi.e.Ac-di-sol (Croscarmellose sodium), Polyplasdone XL-10,Microcrystalline Cellulose pH 102 was Used along with directly compressible dextrose to enhance mouth feel. the formulation prepared by direct Compression method using Ac-di-sol(croscarmellose sodium) 50mg, Polyplasdone XL- 10 -25mg, Microcrystalline Cellulose pH 102- 25mg wasfound tobe better formulation.11
Zade PS,et al., had made an attempt to prepare bitter less fast dissolving tablet of Tizanidine Hydrochloride using Eudragit E 100 as a taste masking agent. Mass extrusion was the technique used for preparing taste masked granules. The tablets were prepared with three super disintegrants e.g. sodium starch glycolate, crosscarmellose sodium and crospovidone. The tablets were evaluated for hardness, drug content and friability and disintegration time. The disintegration in oral cavity was also tested and was found to be 22 sec. Other tablets were prepared by using camphor as sublimating agent. It was concluded that tablets prepared by addition of superdisintegrant has less disintegration time than those prepared by sublimation method.12
Raguia AS,et al., developed lyophilized orally disintegrating tablet (ODT) that enhanced the in vitro dissolution and in vivo absorption of Nimesulide (NM), a drug with poor solubility and poor bioavailability. The ODTs were prepared by freeze-drying an aqueous dispersion of Nimesulide containing a matrix former, a sugar alcohol, and a collapse protectant. Results obtained from disintegration and dissolution studies showed that lyophilized ODTs disintegrated within few seconds and showed significantly faster dissolution rate of NM compared to the plain powder drug and NM in commercially available immediate release tablet Sulide. The results of in-vivo study showed faster rate of absorption of Nimesulidefrom ODT than conventional immediate release tablet in healthy subject using randomized cross over design.13
Keny RV,et al., prepared mouth disintegrating tablet of Rizatriptan benzoate using superdisintegrantcrosspovidone, carboxymethyl cellulose calcium,Indion 414 & Indion 234 using direct compression method.The formulation containing combination of crosspovidoneIndion 234 was found to give best result.14
6.3 OBJECTIVES OF THE STUDY:
The objectives of the proposed study are as follows:

To develop orodispersivetablets.
Compatibility study of drug with differentsuperdisintegrants and additives.
Evaluation of the prepared orodispersive tablets.

MATERIALS AND METHODS:
7.1SOURCE OF DATA:

Reference books.
Web resources.
Indian journal of pharmaceutical sciences.
International journal of pharmaceutics.
European journal of pharmaceutics and biopharmaceutics.
International journal of research pharmaceutical sciences.

7.2METHOD OF COLLECTION OF DATA:
A)MATERIALS :

Drug - antihypertensive drug
Superdisintegrants–crospovidone, sodium starch glycolate, etc.

Tablet excipients and other reagents required for preparation of orodispersivetablets will be procured from standard company sources.
B) METHOD OF PREPARATION:
The active agent and excipients will be formulated into tablet bysuitable technique to give orodispersible tablets of an antihypertensive drug.
C) EVALUATION STUDIES:

Precompression studies

Bulk density
Tapped density
Carr’s index
Angle of repose

Post compression studies

Hardness
Friability
Weight variation
Content uniformity
Disintegration study
D) IN VITRO DRUG RELEASE STUDY:
The in vitrodissolution study will be carried out in USP XXIVdissolution test apparatus. The dissolution medium consists of phosphate buffer (pH 6.8).A 900 ml of the dissolution fluid is used at 37±0.5 ºC with stirring speed of 50 RPM. Samples of specified volume are withdrawn at specific time intervals by replacing with same dissolution medium and samples are analyzed by measuring the absorbance at 230 nm by UV spectrophotometer.
7.3DOESTHIS STUDY REQUIRE ANY INVESTIGATIONSOR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY:
- No-
7.4ETHICAL CLEARANCE :
Not Applicable
LIST OF REFERENCES:
1.Bhowmik D, ChiranjibB, Krishnakanth, Pankaj, Chandira RM. Fast Dissolving Tablet: An Overview. J ChemPharm Res 2009;1(1):163-77.
2.Manivannan R. Oral disintegrating tablets: a future compaction. Int J Pharm Res Dev 2009 Dec;1(10):1-10.
3.Wagh MA, Kothawade PD, Salunkhe KS, Chavan NV, Daga VR. Techniques used in orally disintegrating drug delivery system. Int J Drug Del.2010;(2):98-107.
4.KD Tripathi. Essentials of Medical Pharmacology. 6thed. New Delhi: Jaypee Brothers Medical Publishers(P) Ltd.
5.Bedi N,Kalia A, Khurana S.Formulation and Evaluation of Mouth Dissolving Tablets ofOxcarbazepine. Int J PharmPharmSci 2009 Nov-Dec;1(1):12-23.
6.Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of Valsartan.Int J PharmPharmSci 2009 July-Sep;1(1):219-26.
7.Raghavendra RAO NG,Kulkarni U, RaoKd, Suresh Dk. Formulation And Evaluation Of Fast Dissolving Tablets Of Carbamazepine Using Natural SuperdisintegrantPlantagoOvataSeed Powder And Mucilage. Int J PharmaPharmSci 2010;2(2):70-74.
8.Wagh MP, Yewale CP, Zate SU, Kothawade PI, Mahale GH. Formulation and evaluation of fast dispersible tablets of Aceclofenac using different superdisintegrant.Int J PharmPharmSci 2010;2(1):154-57.
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 Feb;1(12):1-7.
10.ArunArya, Sharma S, Kumar J, Chandra A, Jaiswal P. Formulation and Evaluation of Mouth Dissolving Tablets of Ranitidine HCl. Int J Pharm Tech Res 2010 Apr-June;2(2):1574-77.
11.UmalkarDG, 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 PharmSci Res 2010; 2(8):527-33.
12.Zade PS, Kawtikwar PS, Sakarkar DM. Formulation, Evaluation and Optimization of Fast dissolving tablet containing Tizanidine hydrochloride.International Journal ofPharmTech Research 2009; 1(1): 34-42
13.Raguia AS, Iman SA, Rehab NS. In vitro and in vivo evaluation of Nimesulide lyophilized orally disintegrating tablets.European J PharmaBiopharma 2009; 73: 162-71.
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 / Dr. M.S.SRINATHM. Pharm, PhD.
PROFFESOR
DEPT. 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 / Mr. S. P. THAKKERM. Pharm
PROFFESOR & HEAD,
DEPT. 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.