FORMULATION AND EVALUATION OF DELAYED RELEASE …



FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF FLUOROQUINOLONE DERIVATIVE

SYNOPSIS FOR

M. PHARM. DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA

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BY

NAGABHUSHAN B.S

I M. PHARM.

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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 |NAGABHUSHAN B.S |

| |letters) |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. |

| |Screening of GRAS listed excipients to select the most effective components to develop an orodispersible tablet. |

| |Selection of appropriate polymer in correct ratio to mask the taste. |

| |Selection of appropriate preparation methodology. |

| |Evaluation of the developed formulation for hardness, friability, drug content, disintegration time etc. |

| |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 |

| | |

| |List of references: |

|8. |1. Chandira MR, Mouth dissolving tablet. Pharmaceutical technology transfer, lisensing and regulatory affairs network. |

| | 2009. |

| |2. Sharma S. New Generation of Tablet: Fast Dissolving Tablet. . 2008; 6. |

| | |

| |3. Fluoroquinolone Antibiotics classification, uses and side effects. |

| |http:// 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. |

| | | |

|9. |Signature of the candidate | |

| | |(NAGABHUSHAN B.S) |

| | | |

|10. |Remarks of the guide: |Recommended for research and submission of dissertation. |

|11. |Name and Designation (in block letters) | |

| |11.1. Guide |mrs.Brahmani PRIyadarshini S.R., |

| | |ASSociate professor, |

| | |Department of Pharmaceutics, |

| | |Dayananda Sagar College of Pharmacy, |

| | |Kumaraswamy Layout, |

| | |Bangalore-560078. |

| | | |

| | | |

| | | |

| | | |

| |11.2. Signature | |

| |11.3. Co-guide if any |Not applicable |

| |11.4. Signature | |

| |11.5. Head of the department |Dr. B.WILSON, |

| | |Professor & Head, |

| | |Department of Pharmaceutics, |

| | |Dayananda Sagar College of Pharmacy, |

| | |Kumaraswamy Layout, |

| | |Bangalore-560078. |

| | | |

| | | |

| | | |

| |11.6. Signature | |

|12. |12.1. Remarks of the principal | |

| | |Dr. V. Murugan, |

| | |Principal, |

| | |Dayananda Sagar College of Pharmacy, |

| | |Kumaraswamy Layout, |

| | |Bangalore-560078 |

| | | |

| | | |

| | | |

| | | |

| | | |

| |12.2 Signature | |

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