FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF FLUOROQUINOLONE DERIVATIVE

SYNOPSIS FOR

M. PHARM. DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA

BY

NAGABHUSHAN B.S

I M. PHARM.

Department of Pharmaceutics

Dayananda Sagar College of Pharmacy

2009
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE-II

PROFAMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate and address (in block letters) / NAGABHUSHAN B.S
I M. PHARM.,
DEPARTMENT OF PHARMACEUTICS,
DAYANANDA SAGAR COLLEGE OF PHARMACY,
KUMARASWAMY LAYOUT,
BANGALORE-560078.
PERMANENT ADDRESS
# NO 26, KRUMBIGAL ROAD,
CHIKKAMAVALLI,
BANGALORE 560004
2. / Name of the institute / Dayananda Sagar College of Pharmacy, Shavige Malleswara Hills,
Kumaraswamy Layout,
Bangalore-560078,
Karnataka.
3. / Course of study and subject / Master of Pharmacy in Pharmaceutics
4. / Date of admission to course / 21st May -2009
5. / Title of the project:
“FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF FLUOROQUINOLONE DERIVATIVE”
6.. / Brief resume of the intended work:
6.1 Need of the study:
Oral formulations have wide acceptance and solid dosage forms are popular because of ease of administration, accurate dosage, self-medication, pain avoidance and most importantly the patient compliance. Tablet is the most popular among all dosage forms existing today because of its convenience of self administration, compactness and ease of manufacturing; however, hand tremors, dysphasia in case of geriatric patients, the underdeveloped muscular and nervous systems in young individuals and in case of uncooperative patients, the problem of swallowing is common phenomenon which leads to poor patient compliance. Often times people experience inconvenience in swallowing tablet when water is not available, in the case of the motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic condition and bronchitis1.
To overcome these drawbacks, mouth dissolving tablets (MDT) or orally disintegrating tablets; (ODT) has emerged as alternative oral dosage forms. These are novel types; of tablets that disintegrate/dissolve/ disperse in saliva within few seconds. The basic approach used in development of MDT is the use of superdisintegrants, which provide instantaneous disintegration of tablet after putting on tongue, thereby releasing the drug in saliva. The bioavailability of some drugs may be increased due to absorption of drugs in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into the stomach. Moreover, the amount of drug that is subject to first pass metabolism is reduced as compared to standard tablets2.
.
Fluoroquinolones are widely used class of antibacterials as they have a wide spectrum of activity. They are used in urinary tract infections (norfloxacin, lomefloxacin, enoxacin, ofloxacin, ciprofloxacin, levofloxacin, gatifloxacin, trovafloxacin), prostatitis (norfloxacin, ofloxacin, trovafloxacin), acute sinusitis (ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin (Avelox), trovafloxacin), acute exacerbations of chronic bronchitis (levofloxacin, sparfloxacin (Zagam), gatifloxacin, moxifloxacin, trovafloxacin), acute exacerbations of chronic bronchitis (levofloxacin, sparfloxacin (Zagam), gatifloxacin, moxifloxacin, trovafloxacin) and community –acquired pneumonia (levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, trovafloxacin) 3.
In case of chronic bronchitis, patients face difficulty in swallowing the conventional dosage form (tablets). Hence to overcome this problem, attempts will be made to formulate an orodispersable tablet containing a fluoroquinolone drug.
6.2 Review of literature
An attempt was made to improve the onset of action of terbutaline sulfate used in the treatment of asthma. Fast dissolving tablets of terbutaline sulfate4 were prepared by the direct compression method after incorporating superdisintegrants in different concentrations. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, wetting time, drug content, water absorption ratio, in vitro disintegration time and in vitro drug release. The authors reported that the formulation containing 5% w/w concentration of polyplasdone XL was the best, which releases up to 99.33% of the drug in 10 min.
An attempt was made to improve the onset of action of salbutamol sulfate, a bronchodilator, used commonly in the treatment of asthma. Fast dissolving tablets of salbutamol sulphate5 were prepared using sublimable ingredients. Evaluation of the tablets showed that all the tablets were found to be within official limits and the disintegration time for the formulations ranged from 5s to 40s. All the formulation containing microcrystalline cellulose and ammonium bicarbonate showed the least disintegration time of 5s.
Khan et al, have formulated a rapid disintegrating tablet (RDT) of the taste-masked ondansetron HCl6. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. The complex with drug-polymer ratio of 8:2 did not show drug release in SSF and hence considered taste masked. Therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1:1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t90, 60 seconds) compared with marketed formulation (t90, 240 seconds). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity.
Singh et al, have formulated orodispersible tablets of meloxicam7. The tablets were made by non-aqueous wet granulation using crospovidone and mannitol. Formulated orodispersible tablets were evaluated for weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio and in vitro drug release. The results showed that the presence of a superdisintegrant and mannitol is desirable for orodispersion. All the formulations satisfied the limits of orodispersion with dispersion.
Radke et al, have prepared orodispersible tablets of baclofen8 using various concentrations of superdisintegrant agents like Ac-Di-Sol, crospovidone, sodium starch glycolate by direct compression method. Nine formulations having superdisintegrants at different concentration levels were prepared. These tablets were evaluated for drug content, weight variation, friability, hardness, wetting time and in vitro disintegration time. Among the formulations tablets of batch F3 containing Ac-Di-Sol showed superior organoleptic properties along with excellent in-vitro disintegration time and drug release as compare to other formulations. It was concluded that superdisintegrants addition technique is a useful method for preparing orodispersible tablets by direct compression method.
Ketan et al, have developed orodispersible tablets of atenolol9 containing camphor, kyron-T 314, and lactose were prepared by direct compression technique. Camphor was sublimed by exposure of tablet to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time.. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of kyron-T 314. The systematic formulation approach helped in understanding the effect of formulation processing variables.
Rajitha et al, have formulated orodispersible tablets (ODT) of buspirone10 by wet granulation and direct compression techniques. The optimized formulation was also prepared by freeze drying method. The influence of superdisintegrants, crospovidone, croscarmellose sodium and sodium starch glycolate at three levels on disintegration time, wetting time and water absorption ratio were studied. Tablets were evaluated for weight and thickness variation, disintegration time, drug content, in vitro dissolution, wetting time and water absorption ratio. The results showed that the tablets containing crospovidone exhibit quick disintegration time than tablets containing croscarmellose sodium and sodium starch glycolate. Good correlation was observed between water absorption ratio and DT. Thus rapid disintegrating tablets of buspirone can be prepared by using crospovidone and other excipients at optimum concentration.
Singh et al, have prepared fast disintegrating combination tablets of Omeprazole and Domperidone11 by using pertinent disintegrant. The tablets were prepared using mannitol as diluent and sodium saccharin as sweetening agent along with three different levels of disintegrant. The superdisintegrant used in this study were Kollidon CL, Ac-Di-Sol and SSG. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT) and dissolution study. Using the same excipients, the tablets were prepared by direct compression and were evaluated in the similar way. Drug content was estimated by using HPLC method and also assay of sample was compared with standard drugs (Omeprazole and Domperidone). From the results obtained, it was observed that the tablet formulation prepared with 4.76% Ac-Di-Sol (internally cross linked form of sodium carboxymethylcellulose) ie.10 mg showed disintegration time of 15 seconds in vitro. Also the hardness, friability, dissolution rate and assay of prepared tablets (batch F7) were found to be acceptable according to standard limits.
Ravi kumar et al, have developed Orodispersible tablets of haloperidol12 by wet granulation technique using camphor as subliming agent and sodium starch glycolate together with croscarmellose sodium as superdisintegrants. The porous granules were then compressed in to tablets. The formulations were evaluated for weight variation, hardness, friability, drug content, wetting time, in vitro and in vivo dispersion, mouth feel and in vitro dissolution. All the formulations showed low weight variation with dispersion time less than 45 seconds and rapid in vitro dissolution. The results revealed that the tablets containing subliming agent had a good dissolution profile. The drug content of all the formulations was within the acceptable limits. The optimized formulation showed good release profile with maximum drug being released at all time intervals. It was concluded that fast dissolving tablets with improved haloperidol dissolution could be prepared by sublimation of tablets containing suitable subliming agent.
Shishu et al, have formulated taste masked rapidly disintegrating tablets of ofloxacin13. Taste masking was achieved using a pH sensitive polymer Eudragit E-100 (aminoalkylmethacrylate copolymers). Extrusion followed by crushing technique was used to prepare taste-masked granules. Taste masked granules were directly compressed into tablets using microcrystalline cellulose (MCC) as directly compressible filler and sodium starch glycolate (SSG) as a super disintegrant. The tablets were optimized for tensile strength and fast disintegration characteristics by varying the amounts of MCC and SSG. Finally the optimized dosage form was subjected to various evaluation tests like pharmacopoeial tests, in vitro drug release, disintegration time in oral cavity, wetting time and panel testing for taste assessment. Panel testing data indicated successful formulation of oral fast disintegration tablets with a good taste.
6.3 Objective of the study:
The main objective of the project is to develop an orodispersible tablet containing a fluoroquinolone derivative.
Ø  Screening of GRAS listed excipients to select the most effective components to develop an orodispersible tablet.
Ø  Selection of appropriate polymer in correct ratio to mask the taste.
Ø  Selection of appropriate preparation methodology.
Ø  Evaluation of the developed formulation for hardness, friability, drug content, disintegration time etc.
Ø  Optimization of the formulations.
7. / Materials and methods
7.1 Source of data:
Official Pharmacopoeia, Standard books, International journal of Pharmaceutical sciences, Tropical journal pharmaceutical research, Indian Journal of Pharmaceutical Sciences, International journal of chemtech research, IJPER, International journal of pharmtech research, Asian journal of pharmaceutics, Asian journal of pharmaceutical and clinical research, International journal of pharmacy and Pharmaceutical sciences, AAPS pharmscitech, Pharmaceutical database and internet.
Materials are obtained from authentic dealers.
7.2 Method of collection of the data (including sampling procedure, if any):
The pharmacological details of the drug will be collected from various standard books, journals and other sources like research literature databases such as Medline, Pubmed, Science direct, etc.
Experimental data will be collected from the evaluation of designed formulation and then subjecting the formulation to different studies such as preformulation, hardness, friability, drug content, disintegration time etc.
7.3. Does it require any investigation or interventions to be conducted or patients or other humans or animals? If so please describe briefly:
No
7.4. Has ethical clearance been obtained from your institute in case of 7.3
Not applicable
8. / List of references:
1. Chandira MR, Mouth dissolving tablet. Pharmaceutical technology transfer, lisensing and regulatory affairs network. www.Farmavita.net 2009.
2. Sharma S. New Generation of Tablet: Fast Dissolving Tablet. www.Pharmainofo.net. 2008; 6.
3. Fluoroquinolone Antibiotics classification, uses and side effects.
http:// EzineArticles.com 2006.
4. Rangasamy M, Ayyasamy B, Raju S, Gummadevelly S. Design and evaluation of the fast dissolving tablet of Terbutaline sulphate. Asian journal of Pharmaceutics 2009; 215-217.
5. Suresh S, Pandit V and Joshi HP. Preparation and evaluation of mouth dissolving tablets of Salbutamol sulphate. Indian J Pharm Sci 2007; 69:467-469.
6. Khan S, Kataria P, Nakhat P, and Yeole P. Taste masking of Ondansetron Hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets. AAPS Pharmscitech 2007; 8:E1-E7.
7. Singh J and Singh R. Optimization and Formulation of orodispersible tablets of Meloxicam. Trop J Pharm Res 2009; 8(2):153-159.
8. Radke RS, Jadhav JK, Chajeed MR. Formulation and evaluation of orodispersible tablets of baclofen. Int J ChemTech Res 2009; 1(3):517-521.
9. Ketan RM, Akshay KR, Bhavin VA, Rajesh PK, Ruchi VB, Neha MR, Jignasa MG. Formulation, design and optimization of orodispersible tablets of Atenolol. Int J PharmTech res 2009; 1(4):1559-1563.
10. Rajitha K, Shravan Kumar Y, Adukondalu D, Ramesh Gannu and Madhusudan
rao Y. Formation and evaluation of Orally Disintegrating Tablets of Buspirone. International journal of pharmaceutical sciences and nanotechnology 2009; 1(4):327-334.
11. Singh SK, Mishra DN, Jassal R, Soni P. Fast disintegrating combination tablets of omeprazole and domperidone. Asian journal of pharmaceutical and clinical research 2009; 2(4):54 -62.
12. Ravi kumar, Patil MB, Patil SR, Paschapur MS. Development and characterization of melt-in-mouth tablets of haloperidol by sublimation technique. International journal of pharmacy and pharmaceutical sciences 2009; 1(1):65-73.
13. Shishu, Kapoor VR and Kamalpreet. Taste masking and formulation of ofloxacin rapid disintegrating tablets and oral suspension. Indian J Pharm Educ Res 2009; 43(2):150-155.