FORMULATION AND EVALUATION OF FLOATING TABLETS FOR

ANTIBIOTICS

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

BY

VENKATESWARLU PUNAGANTI

I M.PHARM

UNDER THE GUIDENCE OF

B.APPARAO

ASST.PROFESSOR

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY

KARNATAKA COLLEGE OF PHARMACY

BANGALORE-560064

(2011-2012)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

PROFORMAT FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of thecandidate and address: / VENKATESWARLU. PUNAGANTI
Karnataka College of Pharmacy
#33/2, Thirumena Halli
Hegde Nagar Main Road
Bangalore-560064.
PERMANENT ADDRESS
S/O P.BALAVEERAIAH
N.T.R colony
Seethanagulavaram(Vil&post)
Tarlupadu(M)
Prakasham(Dist).
Andhrapradesh-523332
2. / Name of the Institute: / Karnataka College of Pharmacy
#33/2, Thirumena Halli
Hegde Nagar Main Road
Bangalore-560064.
3. / Course of the Study & Subject: / Master of Pharmacy in
pharmaceutical Technology
4. / Date of admission to the course: / 13-JULY-2011
5. / TITLE OF TOPIC :
FORMULATION AND EVALUATION OF FLOATING TABLETS FOR ANTIBIOTICS
6. / BRIEF RESUME OF THE INTENDED WORK:TIVIT
6.1 / Need of Study:
Oral administration is the most versatile, convenient and commonly employed route of drug delivery for systemic action. Indeed, for controlled release system, oral route of administration has received the more attention and success because gastrointestinal physiology offers more flexibility in dosage form design than other routes. Development of a successful oral controlled release drug delivery dosage form requires an understanding of three aspects: (1) gastrointestinal (GI) physiology (2) physiochemical properties of the drug and (3) dosage form characteristics.
Novel oral controlled dosage form that is retained in the stomach for prolonged and predictable period is of major interest among academic and industrial research groups. One of the most feasible approaches for achieving prolonged and predictable drug delivery profile in the GI tract is to control gastric residence time (GRT). Dosage form with prolonged GRT or gastro-retentive dosage form (GRDF) provides an important therapeutic option (3).
Various approaches for preparation of gastroretentive drug delivery system include floating systems, swellable and expandable systems, high density systems, bioadhesive systems, altered shape systems, gel forming solution or suspension system and sachet systems. Among these, the floating dosage form has been used most commonly. The floating systems include gas-generating systems, noneffervescent systems and raft forming systems.
Current research work of formulatinga floating drug delivery systems by using an antibiotichaving the properties of shorter half life, low bio availability, high acidic stability,short retention timethrough oral route is a useful candidate for controlled release dosage form to remain buoyant, stability in the acidic environmentand enhances the bioavailability is usefulfor gastro-retentive drug delivery system
6.2 / Review of Literature:
  • The formualtion and evaluation of floating drug delivery system containing clarithromycin for helicobacter pylori. Tablets containing hydroxypropylmethylcellulose(hpmc), drug and different additives were compressed using wet granulation and d-optimal design technique.The optimizedformulation was obtained using 62.5% clarithromycin, 4.95% hpmc k15m, 18.09% hpmc k4m, 12.96%sodium bicarbonate which gave floating lag time < 30 s with a total floating time > 10 h, in vitro release profilevery near to the target in vitro release profile and follows anomalous diffusion as well as zero order pattern of release1.
  • The study on formulation and evaluation of floating tablets of furosemide. Floating tablet of furosemide (f) were prepared by direct compression technique. Furosemide was chosen as model drug because it is slightly soluble in water and poorly absorb from lower intestine. Peg-6000 is used as complexing agent for increasing solubility of furosemide in water. Hydroxypropylmethylcellulose, sodium bicarbonate and carbapole were used as matrixing agent gas generating agent and floating enhancers respectively. The data of in-vitro dissolution study shows that the zero order plots were foundto be fairly linear as indicated by their high regression value (r2=0.9772 to 0.9911). To confirm the exactmechanism of drug release from different formulation, the data was fitted to korsmeyer peppas equation.Regression values were from 0.9862 to 0.9963 which indicates linearity2.
  • Studies on formulation and evaluation of floating tablets of ciprofloxacin hcl. In the present study, it was aimed to formulate floating tablet of ciprofloxacin hcl with hpmc and carbomer in different proportion (4%, 8% and 12%) by direct compression techniques using polymers lactose, magnesium streate, talc with sodium bicarbonate. All the prepared formulation were found to complies with the official tests like precompression parameter like angle of repose and post compression parameters like shape, tablet dimensions, hardness, friability test, weight variation test, floating test, content uniformity and in-vitro dissolution study. In-vitro release studies were carried out using usp xxii dissolution test apparatus. The mean percentage of ciprofloxacin released at various time intervals was calculated and plotted against time. The mechanism of drug release with all the formulations was dominantly diffusion and followed zero order kinetics. It was observed that the integrity of the drug is not affected by formulation procedure. The results revealed the drug polymer ratio showed greater drug release than other formulations3.
  • Effervescent floating tablet of amlodipineBesylate.amlodipine besylate effervescent floating tablets were developed in ten different formulations (f1 to f10) by employing different grades of polymers and effervescent agents such as sodium bicarbonate and citric acid. The formulations were evaluated for various physical parameters, buoyancy studies, dissolution parameters and drug released mechanisms. F10 formulation showed maximum floating time of 24 hours and gave slow and maximum drug release of amlodipine besylate spread over 24 hours and whereas amlodipine besylate released from marketed tablet was rapid and maximum within 12 hours4.
  • In vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose (hpmc, methocel k100m cr), compritol 888 ato, alone or in combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating properties were investigated. A 32 factorial design was applied to systematically optimize the drug release profile.the linear regression analysis and model fitting showed that all these formulations followed korsmeyer and peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards to the buoyancy of the tablets5.

  • Formulation and in vitro evaluation of floating matrix tablets of atenolol. Nine formulations of atenolol containing varying concentrations of polymers were designed by optimization. The floating matrix tablets of atenolol were prepared by direct compression method. The prepared tablets were evaluated for physicochemical parameters. All the formulations showed good matrix integrity and retarded the release of drug for eight hours. The swelling studies of all the formulations showed that formulations containing xanthan gum has higher swelling indices than hpmc k100m and hpmc k4m. It can be concluded that formulations with higher swelling indices retarded the release of drugs more than those with lower swelling indices6.

  • Preparation and evaluation of gastro retentive floating tablets of mebendazole. The purpose of this research was to prepare a gastro retentive drug delivery system of mebendazole. Chitosan and hydroxypropyl methyl cellulose of various viscosity were used. Sodium bicarbonate was incorporated as a gas‐generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. The specific study was carried out to formulate such a dosage form that can neutralize the acidity locally in the stomach. The granulation was formed by fluidized bed processor in which top spray technique was adopted for forming the granules7.
  • Studied on formulation and evaluation of floating tablet of atenolol:The drug release behavior of the natural and synthetic polymer was compared according to obtained data. It was higher from the f1 formulation prepared by direct compression. The formulation with guar gum and xanthum gum shows better sustained release effect than hpmc different grade. The developed floating tablets of atenolo may be used in clinic for prolonged drug release for at least 12hrs, thereby improving the bioavailability and patient compliance8.
  • Oral floating tablet of cephalexin using the hydrophilic polymer, hydroxy propyl methyl cellulose (hpmc), gas generating agent sodium bicarbonate and citric acid. The results of factorial design indicated that high level of hpmc k100m and citric acid favors preparation of floating sustained release tablet of cephalexin. The granules were prepared by wet granulation method and evaluated for their granules properties. Tablets were compressed by kbr press and evaluated with different parameters like diameter, thickness, average weight, hardness, friability, drug content, in vitro buoyancy study, swelling characteristics, scanning electron microscopy, kinetic release data. Hardness was found to being the range of 13 ± 0.23 to 13 ± 0.40 kg/cm , the percent friability was in the range of 0.0010 ± 0.02 to 0.0027 ± 0.01, and tablets showed 99.63 ± 0.12 to 115.73 ± 0.13 of the labeled amount of cephalexin indicating uniformity content. The tablets containing cef released 72.28 to 99.461 % of drug at the end of 12 hr by in vitro release study. The drug release followed the korsmeyer and peppas model controlled mechanism of cephalexin tablet9.
  • Statistical optimization of gastric floating system for oral controlled delivery of clarithromycin. Statistical experimental design and data analysis using response surface methodology is also illustrated. A 32 factorial design for the controlled release of clarithromycin was used with two formulation variables: x1 (hpmc k4m) and x2 (citric acid). Nine formulations were prepared and dissolution studies and floating characteristics were performed on these formulations. The dissolution data obtained were then fitted to the pcp disso version 2.08 software. Linear regression analysis and model fitting depicted that the formulations followed hixon crowell model. The two formulation variables were found to be significant for the release properties (p < 0.05), while citric acid loading was found to be significant for floating lag time. The quadratic mathematical model developed could be used to further predict formulations with desirable release and floating properties10.

6.3 / Objective of the Study:
The objective of the study is as follows:
1) The current study is to develop an ideal floating drug delivery system.
2) Formulation of floating tablets by suitable method.
3) Evaluation of floating tabletsfor their physicochemical studies.
4) Stability studies for selected formulations.
.
7.
7.1
7.2 / Materials & Methods:
Materials
Antibiotic and polymers will be procured from pharma grade suitable manufacturer. Other reagents will be of Analytical grade.
Methods
1) Preparation of floating tablets by Suitable Technique
2) Evaluation
a) Weight Variation
b) Drug Content
c) Hardness
d) Buoyancy / Floating test
e) Tablet density
f)Drug release studies
3) Stability studies as per ICH guidelines.
7.3 / Source of Data:
  • The data will be obtained from the literature survey and Internet source.
  • Digital Library RGUHS Library, Bangalore.
  • Library, Karnataka College of Pharmacy, Bangalore.
  • The data will be obtained on experimental work.

7.4 / Method of Collection of Data (including sampling procedure, if any) :
Data will be collected from the pre-formulation, formulation, evaluation studies and stability studies. In-vitro dissolution studies will be used as criteria for assessing the different formulation for their therapeutic efficacy and drug release. And stability studies for their stability property.
7.5 / Does the study require any investigations or interventions to be conducted
On patients or other human or animals ? If so please describe briefly
DOES NOT REQUIRED
7.6 / Has the Ethical Clearance been obtained from your Institution in case of 7.5 ?
NOT APPLICABLE
8. / LIST OF REFERENCES:-
  1. Sanjay S Patel, S. Ray And RS Thakur Formualtion And Evaluation Of Floating Drug Delivery System Containing Clarithromycin For Helicobacter Pylori. Acta Poloniae Pharmaceutica Ñ Drug Research 2006; 63(1):53-61
  2. Vishal G. Karkhile, Dr. Ritesh R. Karmarkar, Manish A. Sontakke, Shyam D Badgujar,Formulation And Evaluation Of Floating Tablets Of Furosemide. Ijprd 2010;(1):12-17
  3. Ajay Bagherwal, Dinesh Kumar Patidar And Pradeep Sharma, Studies On Formulation And Evaluation Of Floating Tablets Of Ciprofloxacin Hcl Pharmacie Globale (Ijcp) 2010; 5 (02):34-39
  1. Pare A, Yadav SK And Patil,Formulation And Evaluation Of Effervescent Floating Tablet Of Amlodipine Besylate, Research J. Pharm. And Tech. 2008; 1(4):23-28
  2. Gambhire Mn, Ambade Kw, Kurmi Sd, Kadam Vj, Jadhav Kr. Development And In Vitro Evaluation Of An Oral Floating Matrix Tablet Formulation Of Diltiazem Hydrochloride. Aaps Pharmscitech 2007;8(3):28-34
  3. VD Havaldar, AS Kulkarni, RJ Dias, NH Aloorkar, KK Mali, Floating Matrix Tablets Of Atenolol: Formulation And In Vitro Evaluation Cdd 2009; 3(4):286-291
  4. Krunal Patel M, Biswajit Biswal, Nabin Karna, Janki Patel, Preparation And Evaluation Of Gastro Retentive Floating Tablets Of Mebendazole, Int J Pharma Sci.2010; 2(1):6-10
  5. Patel Ishvar C., Jitendra Chandrashekhar Hugar, Dayakar Rao Kalakuntla, Formulation And Evaluation Of Floating Tablet Of Atenolol: Functionality Of Natural And Synthetic Polymer, Ijpi’s Journal Of Pharmaceutics And Cosmetology(2011); 1(3):15-19
  6. Anilkumar J Shinde, Manojkumar S Patil And Harinath N More,Formulation And Evaluation Of An Oral Floating Tablet Of CephalexinIndian J Pharm Educ Res 2010;44(3):56-62
  7. SR Shahi, NV Shinde, GR Agrawal, SA Shaikh, SS Shaikh, VG Somani, MA Kale, PB Shamkuwar, AN Padalkar,Statistical Optimization Of Gastric Floating System For Oral Controlled Delivery Of Clarithromycin, Rjc Rasayan J Chem2008;1(2):367-377

9. / Signature of the Candidate / (P.Venkateswarlu)
10. / Remarks of the Guide:
The topic selected for dissertation is satisfactory. Adequate equipment & chemicals are available to carry out the project work.
11. / Name & Designation (in BLOCK LETTERS)
11.1 / Guide / MR.M.APPARAO,M.PHARM, (PHD)
ASST.PROFESSOR
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BANGLORE-64
11.2 / Signature of Guide / s. OHINI. M.)
(MR.M.APPARAO)
11.3 / Co-Guide / NOT APPLICABLE
11.4 / Signature of Co-Guide / NOT APPLICABLE
11.5 / Head of the Department / DR.B.PRAKASH RAO
HEAD OF DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BANGLORE-64.
11.6 / Signature of HOD: / (DR.PRAKASH RAO)
12.
12.1 / Remarks of the Principal:
All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.2

12.3 / Principal
Signature Of Principal / DR. K.RAMESH
KARNATAKA COLLEGE OF PHARMACY #33/2, THIRUMENA HALLY HEGDE NAGAR MAIN ROAD
BANGALORE-560064.
(K.RAMESH)

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