Development and in-vitro Evaluation of Gastro-Retentive Cefpodoxime Proxetil Floating Microspheres
M.Pharm Dissertation Protocol Submitted to the
Rajiv Gandhi University of Health Sciences,
Karnataka, Bangalore.
By
Mr. Kirtikumar S. Patil B.Pharm
Under the guidance of
Dr. Chandrashekar C. Patil M.Pharm,P.hd
Professor and HOD
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy, Bijapur-586103
2010-2011
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate andAddress
(In block letters) / Mr. KIRTIKUMAR. S. PATIL
2. / Name of the Institution / B.L.D.E.A’s College of Pharmacy, BLDE university campus, Bijapur-586 103
3. / Course of study and subject / M.Pharm in Pharmaceutics
4. / Date of admission to Course / 15-06-2009
5. / Title of the Topic / Development and in-vitro Evaluation of Gastro-Retentive Cefpodoxime Proxetil Floating Microspheres.
6. / Brief resume of the intended work :
6.1 Need for the study
6.2 Review of literature
6.3 Objectives of the study / Enclosure-I
Enclosure-II
Enclosure-III
7. / Material and Methods :
7.1 Source of data : Enclosure-IV
7.2 Method of collection of data (including sampling procedure, if any)
: Enclosure-IV
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
: No
7.4 Has ethical clearance been obtained from your institution in case of 7.3
: No
8. / List of References (about 5-9) : Enclosure-V
9. / Signature of candidate
10. / Remarks of the guide / : Enclosure-VI
11. / Name & Designation of
(in block letters)
11.1 Guide
11.2 Signature
11.3 Co-Guide (if any)
11.4 Signature
11.5 Head of Department
11.6 Signature / Dr. CHANDRASHEKAR C. PATIL
Professor and HOD
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy,
BIJAPUR-586 103
---
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Dr. C. C. PATIL
Professor & Head
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy,
BIJAPUR-586 103
12. / 12.1 Remarks of the chairman & principal: This study can be carried out in our
laboratory
12.2 Signature
ENCLOSURE-I
6) Brief resume of the intended work
6.1. Need for the study
To develop oral drug delivery systems, it is necessary to optimize both the residence time of the system within the gastrointestinal tract and the release rate of the drug from the system. Various attempts have been made to prolong the residence time of the dosage forms within the stomach. The prolongation of the gastric residence time (GRT) of delivery devices could be achieved by adhesion to the mucous membranes, by preventing their passage through the pylorus or by maintaining them in buoyant fashion in gastric juice.1
Drugs that are easily absorbed from the gastrointestinal tract (GIT) and have a short half-life are eliminated quickly from the blood circulation, require frequent dosing. To avoid this problem, the oral controlled release (CR) formulations have been developed in an attempt to release the drug slowly into the GIT and maintain a constant drug concentration in the serum for longer period of time. Such oral drug delivery devices have a restriction due to the gastric retention time (GRT), a physiological limitation. Therefore, prolonged gastric retention is important in achieving control over the GRT because this helps to retain the CR system in the stomach for a longer time in a predictable manner.2
Gastro-retentive floating microspheres have emerged as an efficient means of enhancing the bio-availability and controlled delivery of more drugs. The increase in sophistication of delivery technology will ensure the development of increase in number of gastro-retentive drug delivery systems to optimize the delivery of molecules that exhibit low bio availability and extensive first pass metabolism.
A gastric floating drug delivery system can overcome atleast some of these problems and is particularly useful for drugs that are primarily absorbed in duodenum and upper jejunum segments and it can prolong retention time of dosage forms in GIT and thereby improve there the oral bio-availability. The control of gastro-intestinal transit could be the focus of the next decade and may result in new therapeutic possibilities with the substantial benefits for the patients.
Cefpodoxime proxetil is the third generation cephalosporin pro drug which is administered orally with only 50% absolute bio-availability. By formulating the drugs as a controlled action dosage form especially as floating dosage form, its bio-availability may be improved. Because of low bio-availability of Cefpodoxime proxetil due to intestinal lumen hydrolysis may be to some extent prevented. More ever the absorption of cefpodoxime proxetil in upper GIT is more. Floating drug delivery is able to prolong the gastric retention of microspheres and thereby possibly improve oral bio availability of Cefpodoxime proxetil.3
ENCLOSURE-II
6.2. Review of literature
1. Manish Patel et.al, have reported effect of Methocel a floating microspheres of Verapamil Hydrochloride. They have concluded the influence of viscosity and drug to polymer ratio on verapamil HCL. The release and drug loaded floating microspheres in combination with methocel k4m are suitable drug delivery system for verapamil HCL.4
2. Yuveraj Singh, et.al, prepared and evaluated the floating microspheres of verapamil hydrochloride for improving the drug bio-availability by prolongation of gastric residence time by using cellulose acetate, acrycoat S100 and eudragit S100 microspheres loaded with verapamil HCL. They concluded that nature of polymer influence the physical characteristic as well as floating behavior of the microspheres. In-vitro buoyancy confirms the excellent floating properties of cellulose acetate microspheres.5
3. Agarwal G.P et.al, prepared floating microsphere by emulsion solvent diffusion technique consisting of calcium silicate as porous carrier and eudragit S polymer ,studied on effect of various formulation and process variables on internal and external particle morphology, micrometric properties, in-vitro floating behavior, physical state of the incorporated drug, drug loading and in-vitro drug release. The concluded that repaglinide floating microspheres consisting of calcium silicate have proved to be an effective method to achieve the desired release behavior and buoyancy.6
4. Sanming Li et.al, developed the new sustained release floating microspheres by the ionotropic gelation method with calcium carbonate being used as a gas forming agent and used chitosan to enhance the drug encapsulation and delay the drug release into the gelation medium and by coating with Eudragit.7
5. Deepa M.K et.al, concluded that floating microspheres of Cefpodoxime Proxetil were prepared using HPMC and EC, by non-aqueous solvent evaporation method at the higher polymer to drug ratio improved the entrapment efficiency, percentage of yield as well as buoyancy percentage.8
6. Lee JH et.al, prepared microspheres for water soluble drug using Eudragit S 100 by water in oil in oil double emulsion solvent diffusion method. Dichloromethane and corn oil was used as primary and secondary oil phase, tween 80 and span 80 were used as surfactant for stabilizing internal water phase and oil phase. The results indicate indicated that the drug release was pH dependent at 7.4pH.9
ENCLOSURE-III
6.3. Objectives of the study
The present work is planned with the following objectives.
1. To prepare cefpodoxime proxetil floating microsphere by using Non aqueous solvent evaporation method or Double emulsion solvent diffusion method.
2. To examine the resinates for angle of repose, bulk density etc.
3. To study the entrapment efficiency of prepared microspheres.
4. To study the in vitro drug release from floating microspheres.
5. To carry out buoyancy percentage studies of the prepared floating microspheres.
6. Drug polymer interaction is carried out by Scanning electron microscopy, DSC, I.R.
7. To carry out the stability studies on the prepared formulations.
ENCLOSURE-IV
7) MATERIALS AND METHODS
7.1. Source of data
The data will be collected by performing various laboratory experiments, referring journals, text books and other literature.
7.2. Method of collection of data
The whole data is planned to collect from laboratory experiments which includes the following,
1) Compatibility study of drug and with various polymers will be carried out by Using Infrared Spectroscopy, Differential Scanning Colorimeter.
2) Preparation of standard calibration curve of Cefpodoxime Proxetil.
3) Preparation of Cefpodoxime Proxetil floating microspheres by using polymers such as Ethyl cellulose, Hydroxy Propyl Methyl Cellulose (HPMC), Cellulose Acetate, Eudragits, Chitosan etc by Non aqueous solvent evaporation method or Double emulsion solvent diffusion method.
4) Evaluation parameters
i) Flow property of prepared microspheres.
ii) Bulk density of prepared microspheres.
iii) Particle size analysis.
iv) Drug entrapment efficiency.
v) Buoyancy studies.
vi) In-vitro dissolution studies by using dissolution tester USP (XXIII) basket method release.
5) Topographical study by Scanning Electron Microscopy (SEM).
6) The stability studies of the formulations will be carried out as per ICH guidelines and data will be collected.
ENCLOSURE-V
8) List of References
1. Yasunori S., Yoshiaki K., Hirofumi T., Hiromitsu Y. 2004 “In vitro evaluation of floating and drug releasing behaviors of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method” European J. of Pharmaceutics and Biopharmaceutics, 57: 235–243.
2. Gattani Y.S., Kawtikwar P.S., Sakarkar D.M. 2009 “Formulation and Evaluation of Gastro-Retentive Multiparticulate drug delivery system of Aceclofenac”. Int.j.Chem Tech Research, 1:1-10
3. Deepa K., Karthikeyan M. 2009 “Cefpodoxime Proxetil floating microspheres: Formulation and in-vitro evaluation”. Iranian J. Pharm Sci, 5(2): 69-72
4. Manish P.P., Patel M.M., Patel K.N., Patel D.R., Patel U.L. 2009 “Designing and Evaluation of Floating Microspheres of Verapamil Hydrochloride: Effect of Methocel”. Research J. Pharma Dosage Forms and Tech, 1(1): 22-28.
5. Yuveraj S.T., Pushpendra S.N., Garima Rani. 2007 “Development and Evaluation of Verapamil Hydrochloric”. Brazilian J. Pharm Sci, 43: 4-8
6. Agarwal G.P., Sunil K.J., Awasti A.M., Jain N.K. 2005 “Calcium Silicate based microspheres of Repaglinide for Gastro-Retentive floating drug delivery: Preparation and in-vitro characterization”. J. Control. Rel, 107: 300-309.
7. Sanming Li., Ninan Ma., Qifang w., Xiangrong Z., 2008 “Development and Evaluation of new sustained-release floating microspheres”. Int. J. Pharm, 358: 82-90.
8. Deepa K., Karthikeyan.M. 2009 “Cefpodoxime Proxetil floating microspheres: Formulation and in-vitro evaluation”. Iranian J. Pharm Sci, 5(2): 69-72
9. Jung-Haw L., Tea Gwan P., Hoo-Kyun C. 2002 “Effect of formulation and processing variables on the characteristics of microspheres for water soluble drugs prepared by w/o/o double emulsion solvent diffusion method”.Int.J.Pharm, 196:75-83.
ENCLOSURE-VI
10) Remarks of the Guide
The present work is aimed to develop and evaluate the gastro-retentive cefpodoxime proxetil floating microsphere. Cefpodoxime proxetil is the third generation cephalosporin pro drug which is administered orally with only 50% absolute bio-availability. By formulating the drugs as a controlled action dosage form especially as floating dosage form, its bio-availability may be improved. Because of low bio-availability of Cefpodoxime proxetil due to intestinal lumen hydrolysis may be to some extent prevented. More ever the absorption of cefpodoxime proxetil in upper GIT is more. Floating drug delivery is able to prolong the gastric retention of microspheres and thereby possibly improve oral bio availability of Cefpodoxime proxetil. The proposed study can be carried out in our laboratory.
Dr. Chandrasekhar. C Patil
Professor and HOD
Department of pharmaceutics
Research Guide
2