“FORMULATION AND IN VITRO EVALUATION OF ORAL SUSTAINED DELIVERY OF ANTIHYPERTENSIVE DRUG FROM FLOATING MATRIX TABLETS”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA.
BY
NATRAJ MUGUTE
DEPARTMENT OF PHARMACEUTICS
PES COLLEGE OF PHARMACY
BANGALORE
(2011-12)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 /Name of the candidate and address
/ NATRAJ MUGUTEResiding no: 144, 4th cross, Bhuvaneshwari nagar, B.S.K. 3rd Stage. Bangalore-85
PERMANENT ADDRESS
NATRAJ MUGUTE
H.No: 9-5-541, Adarsh colony, behind K.P.T.C.L office.
Bidar-585401
2 /
Name of the institution
/P.E.S. COLLEGE OF PHARMACY
50 FEET ROAD,HANUMANTH NAGAR,
BANGALORE-560050.
3 /
Course of study and subject
/MASTER OF PHARMACY IN PHARMACEUTICS
4 /Date of the admission
/ 29th July 20115 /
Title of the topic:
“FORMULATION AND IN VITRO EVALUATION OF ORAL SUSTAINED DELIVERY OF ANTIHYPERTENSIVE DRUG FROM FLOATING MATRIX TABLETS”2
6. / Brief resume of the intended work:6.1 Need for the study:
· The gastro retentive drug delivery systems are retained in the stomach and assist in improving the oral sustained delivery of drugs. These systems help in continuously releasing the drug before it reaches to the absorption window, thus ensuring optimal bioavailability.
· Drugs that have poor bioavailability because of site-specific absorption from the upper part of the gastrointestinal tract are potential candidates to be formulated as floating drug delivery systems, thereby maximizing their absorption.
· Floating drug delivery system is one of the important approaches to achieve gastric retention to obtain sufficient drug bio-availability. This delivery system is desirable for drugs with an absorption window in the stomach or in upper small intestine. This have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting gastric emptying rate for a prolonged period and the drug is released as a desired rate for the system.
· Hypertension is the term used to describe high blood pressure. Persistent hypertension- risk factor for stroke, heart attack, heart failure, arterial aneurysm. Hypertension is caused by inability of the kidneys to excrete sodium, an overactive rennin-angiotensin system, an overactive sympathetic nervous system.
· The management involves proper planning and control of blood pressure levels. Alpha blockers, Calcium channel blockers, Angiotensin- converting enzyme (ACE) inhibitors, Beta blockers etc., are used for satisfactory management of Hypertension.
· Metoprolol Tartrate is cardioselective beta blocker. It is used in management of hypertension, angina pectoris, cardiac arrhythmias and myocardial infarction. Metoprolol is rapidly absorbed following an oral dose but undergoes extensive first pass metabolism resulting in only 38% oral bioavailability. The biological half life of Metoprolol Tartrate is about 3-7 hrs. Commercially Metoprolol is available as tablets, injections as well as extended release tablets. The oral dose of Metoprolol Tartrate is 25 mg to 400 mg. and intravenous dose is 1-4 mg.
· Several approaches are currently used to prolong gastric retention time. These include floating drug delivery systems, swelling systems, expanding systems, high density systems and other delayed gastric emptying devices. Prolonged gastric retention improves Bio availability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients.
6.2 Review of the literature:
· Narendra C et al studied Optimization of Bilayer Floating Tablet Containing Metoprolol Tartrate as a Model Drug for Gastric Retention. This article discussed a positive application of a computer optimization technique for the development of a bilayer GFDDS in which polymer (HPMC) viscosity grade (K4M or K10M) did not significantly affect the floating and release properties. However, the factor total polymer content-to drug ratio and the polymer-to-polymer ratio did significantly affect the studied dependent variables. The dosage form can control the release, avoid dose dumping, and extend the duration of action of a drug with prolonged floating time. This dosage form holds promise for further in vivo studies, which can be extrapolated for the development of other delivery systems1.
· Li S et al studied statistical Optimization of Gastric Floating System for Oral Controlled Delivery of Calcium. A rotatable, central composite design was performed, and the desired release of calcium from GFDDS was achieved by carefully monitoring the selection of formulation variables. Further, the results from floating studies suggested that the desired floating profile of GFDDS could be achieved while maintaining the desirable release properties of the GFDDS formulation2.
· Patel JK et al studied floating In Situ Gel based on Alginate as Carrier for Stomach-Specific Drug Delivery of Famotidine. This study reports that oral administration of aqueous solutions containing sodium alginate results in formation of in situ gel at the stomach site. The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of calcium chloride significantly affected on the dependent variables like viscosity, drug content, Q50 and Q80. The in-vivo study demonstrated the excellent gel formation in the stomach of the rat and significant anti-ulcer effect of alginate based in situ gel of famotidine over longer period3.
· Tadros MI et al carried out Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: Development, optimization and in vitro–in vivo evaluation in healthy human. Promising controlled-release floating tablets of Cipro HCl were successfully formulated by effervescent technique. Tablets containing HPMC K15M (21.42%, w/w), Na alginate (7.14%, w/w) and NaHCO3 (20%, w/w) (formula F7) or CaCO3 (20%, w/w) (formula F10) showed satisfactory results with respect to floating lag time, total floating duration, swelling ability, adhesion retention period and sustained drug release rates4.
· Sawicki W et al carried out Compressibility of floating pellets with verapamil hydrochloride coated with dispersion Kollicoat SR 30 D. The purpose of this study was to work out a method of compression of floating pellets with verapamil hydrochloride (VH) in a dose of 40 mg. It was assumed that this form should reside in the stomach floating for several hours and gradually release the drug in a controlled way. Compression of pellets into tablets, being a modern technological process, is much more perfect than enclosing them in a hard gelatin capsule5.
· Amit P et al studied formulation development and evaluation of famotidine floating tablet. The purpose of this investigation was to prepare a floating drug delivery system of famotidine. Famotidine having poor absorption in acidic environment (upper GIT). When given orally, it shows the bioavailability near to 50%. To overcome these drawbacks, the present study was undertaken to investigate the floating dosage form of famotidine. Floating tablets were prepared using Direct Compression6.
· Rahman Z et al carried out Design and evaluation of bilayer floating tablets of captopril. The present study was carried out to develop the floating drug delivery with controlled release of captopril using HPMC, K-grade polymer as a carrier. In vitro dissolution studies showed controlled release for 24 h, followed by the Higuchi diffusion mechanism and in vivo studies indicated increased GRT. Thus, results of the current study clearly indicate, a promising potential of the captopril floating system as an alternative to the conventional dosage form. However, further clinical studies are needed to assess the utility of this system for patients suffering from hypertension7.
· Anjankumar PB et al studied formulation and Evaluation of Floating Tablet of Atenolol: Functionality of Natural and Synthetic Polymer The purpose of this research was to prepare a floating drug delivery system of Atenolol in order to increase the gastric residence time (GRT) and comparison of natural and synthetic polymer for better sustained effect. The tablets were prepared by direct compression. The pre and post compression studies were performed by using IP standard formula and procedure. Drug release from the floating drug delivery system was studied using USP ІІ8.
· Patil P et al carried out Formulation and In Vitro Evaluation of Floating Matrix Tablets of Ofloxacin. Floating matrix tablets containing ofloxacin was prepared successfully by using wet granulation technique. Tablets were subjected to various evaluation parameters such as Weight variation, Hardness, Friability, Drug content, Swelling index, in vitro drug release study, in vitro buoyancy study. It was revealed that tablets of all batches had acceptable physical parameters. FT-IR studies revealed that there was no interaction between ofloxacin and other excipients used in the tablets9.
· Kumar PR et al carried out Design and evaluation studies on novel floating tablets for peptic ulcer Treatment. The aim of this study was to develop enteric coated esomeprazole core tablet followed by compression coating with clarithromycin coat granules to obtain a single unit core in coat floating tablet. The tablets were prepared by investigating various porous carriers, cellulosic polymers and natural gums10.
· Kannan C et al carried out Formulation and in vitro Evaluation of Gastro retentive Rosiglitazone maleate Floating Tablets. The present study performed by Formulation and Evaluation of Floating Tablets of Rosiglitazone maleate as a model drug for prolongation of gastric residence time. Floating effervescent tablets were formulated with various materials like hydroxy propyl methyl cellulose (HPMC) K4, K15, K100 at varying concentrations were used for its gel forming release controlling properties, sodium bicarbonate act as a effervescent agent and hydrophobic meltable material like bees wax was used. The tablets were prepared by melt granulation technique and the prepared tablets remained buoyant for more than 12 hours11.
· Anil G et al carried out formulation and evaluation of gastro retentive floating tablets of venlafaxine hydrochloride. The present study was undertaken with an aim to formulation development and evaluation of gastro retentive floating tablets of venlafaxine hydrochloride, which releases the drug in a sustained manner over a period of 12 hours. Three different viscosity grades of Hydroxypropylmethylcellulose (HPMC) namely K4M, K15M, and K100M were used for the preparation of tablets. The tablets were prepared by direct compression and evaluated for tablet thickness, weight variation, tablet hardness, friability, in vitro buoyancy test, in vitro drug release and Fourier transform infrared (FT-IR) spectroscopy12.
· Kulkarni A et al carried out Development and evaluation of regioselective bilayer floating tablets of Atenolol and Lovastatin for biphasic release profile. Bilayer floating tablets having different release profiles for different drugs can be formulated using HPMC K100M and xanthan gum (alone and in combination) to give controlled release of atenolol, and sodium starch glycollate to give immediate release of lovastatin. Hence, this dosage form should be further evaluated for delivery of two drugs from, a single dosage form. Which could improve patient compliance and give better disease management13.
· Thakkar VT et al fabricated and evaluated levofloxacin hemihydrate floating tablets. The effervescent-based floating drug delivery is a promising approach to achieve in vitro buoyancy. The addition of gel-forming polymer (HPMC K4M), release retarding matrixing agent (Gelucire 43/01) and gas generating agent (sodium bicarbonate) was essential to achieve in vitro buoyancy. Formulation F4 showed controlled drug release and adequate floating properties. The kinetics of drug release was best explained by Higuchi model. Further, it was concluded that AUC based mathematical approach can be used to quantify deviation in Higuchi model14.
6.3 Main objectives of the study:
The objectives of the present study are as follows:
1. To carry out preformulation studies of model anti-hypertensive drug
2. To design and develop sustained release floating tablets of anti-hypertensive drug.
3. To carry out the in vitro drug release studies
4. To study the mechanism of drug release from the formulations.
5. To carry out the stability studies of the optimized formulation.
Materials and methods:
7.1 Source of data:
· The data will be obtained from the literature survey and internet source.
· The data will be obtained from the experimental work, which includes formulation of sustained release matrix tablets by using different polymers, evaluation of drug content and stability studies.
7.2 Method of collection of data (including sampling procedures if any):
· The data will be collected from prepared formulations subjected to different evaluation techniques, estimation of drug content, in-vitro drug release and stability studies.
7.3 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
- NO –
7.4 Has ethical clearance been obtained from your institution in case of
7.3?
- Not applicable -
LIST OF REFERENCES:
1. Narendra C, Srinath MS, Babu G. Optimization of Bilayer Floating Tablet Containing Metoprolol Tartrate as a Model Drug for Gastric Retention. AAPS Pharm Sci Tech. 2006;7:34.2. Li S, Lin S, Chien YW, Daggy BP, Mirchandani. HL. Statistical Optimization of Gastric Floating System for Oral Controlled Delivery of Calcium. AAPS Pharm Sci Tech. 2001;2:1.
3. Patel JK, Chavda JR, Modasiya MK. Floating In Situ Gel based on Alginate as Carrier for Stomach-Specific Drug Delivery of Famotidine. Int J Pharm Sci Nanotechnol. 2010;3.
4. Tadros MI. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: Development, optimization and in vitro–in vivo evaluation in healthy human volunteers. Eur J Pharm Biopharm. 2010;74:332-9.
5. Sawicki W, Lunio R. Compressibility of floating pellets with verapamil hydrochloride coated with dispersion Kollicoat SR 30 D. Eur J Pharm Biopharm. 2005;60:153-8.
6. Amit P, Kumar JS, Harishanker P, Tarkeshwar S, Arpit S. Formulation Development and Evaluation of Famotidine Floating Tablet. Int J Pharm Sci. 2010;4(3):224-9.
7. Rahman Z, Ali M, Khar R. Design and evaluation of bilayer floating tablets of captopril. Acta Pharm. 2006;56:49-57.
8. Anjankumar PB, C PI, Hugar JC, Kalakuntla DR. Formulation and Evaluation of Floating Tablet of Atenolol: Functionality of Natural and Synthetic Polymer. IJPI’s J Pharm Cosmetology. 2011;1.
9. Patil P, B SR, Kulkarni SV, Basavaraj, Surpur C, Ammanage A. Formulation and In Vitro Evaluation of Floating Matrix Tablets of Ofloxacin. Asian J Res Pharm Sci. 2011;1:17-22.
10. Kumar PR, Doddayya H, Reddy SR. Design and evaluation studies on novel floating tablets for peptic ulcer treatment. J Adv Pharm Educ Res. 2011;2:159-76.
11. Kannan C, Karunanithi V, Janarthanan S, Dheivasigamani V. Formulation and in vitro Evaluation of Gastro retentive Rosiglitazone maleate Floating Tablets. Int J Chem Pharm Sci. 2010;1:1.
12. Anil G, Satyanarayana T, Suresh Kumar P, Pavani S, C H Narasimha Raju B H, Mohideen S. Formulation and Evaluation of gastro retentive Floating Tablets of Venlafaxine Hydrochloride. Int J Pharm Ind Res. 2011;1.
13. Kulkarni A, Bhatia M. Development and evaluation of regioselective bilayer floating tablets of Atenolol and Lovastatin for biphasic release profile. Iranian J Pharm. 2009;8:15-25.
14. Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. Fabrication and evaluation of levofloxacin hemihydrate floating tablet. Res Pharm Sci. 2008;3:65-72.
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12. /
Signature of the candidate: (NATRAJ MUGUTE)
Remarks of the guide: Recommended.
Name And Designation of: Dr. SATISH C.S.
11.1 Guide Professor & HOD
Department of Pharmaceutics,
P.E.S. College of Pharmacy,
Bangalore-560050.
11.2 Signature
11.3 Co-Guide
NOT APPLICABLE
11.4 Signature
11.5 Head of the department Dr. SATISH C .S.
Professor & HOD,
Department of Pharmaceutics,
P.E.S. College of Pharmacy,
Bangalore -560050. 11.6 Signature
12.1 Remarks of the Chairman and Principal:
Prof. Dr. S. Mohan,
Principal,
P.E.S. College of Pharmacy,
Bangalore-560050.
12.2 Signature
2