Synopsis for M.Pharm Dissertation submitted to the
Rajiv Gandhi University of Health Sciences Karnataka, Bangalore.By
Miss.VEENA.M.CM.Pharm. Part-I
Under the guidance of
Dr.S.K.SENTHIL KUMAR., M.Pharm, Ph.D.
Department of Pharmaceutics,
Bharathi College of Pharmacy,
Bharathinagara.
2011-2012
Rajiv Gandhi University of Health Sciences, Karnataka
Curriculum Development cell
CONFIRMATION FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
Name of the candidate : VEENA.M.C
Address : DEPARTMENT OF PHARMACEUTICS,
BHARATHI COLLEGE OF PHARMACY,
BHARATHI NAGAR, MANDYA,
KARNATAKA-571422.
Name of the institution : Bharathi College of pharmacy, K M Doddi
Course of Study and Subject : M.Pharm in Pharmaceutics
Date of Admission to course :26.07.2011
Title of the Topic : PREPARATION AND EVALUATION OF
POROUS PELLETS LOADED WITH
ANTI- ARRYTHMIC DRUG.
Brief resume of the intended work : Attached
Signature of the student :
Guide Name : Dr.S.K.SENTHIL KUMAR.,M.Pharm.Ph.D
Remarks of the Guide : Recommended
Signature of the Guide :
Co-Guide Name : Not Applicable
Signature of the Co-Guide : Not applicable
HOD Name : Dr.S.K.SENTHIL KUMAR.,M.Pharm.,Ph.D,
Signature of the HOD :
Principal Name : Dr.T.TAMIZH MANI ,M.Pharm.,Ph.D.,
Principal Mobile No. : 09980002272
Principal E-mail ID :
Remarks of the Principal : Recommended & Forwarded
Principal Signature :
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATEAND ADDRESS (IN BLOCK LETTERS) / VEENA.M.C
M PHARM, PART –I,
DEPARTMENT OF PHARMACEUTICS,
BHARATHI COLLEGE OF PHARMACY,
BHARATHINAGARA, MANDYA, KARNATAKA-571422.
2. /
NAME OF THE INSTITUTION
/ BHARATHI COLLEGE OF PHARMACY,BHARATHINAGARA.
3. /
COURSE OF STUDY AND SUBJECT
/ MASTER OF PHARMACY IN PHARMACEUTICS.4. / DATE OF ADMISSION OF COURSE / 26-07-2011
5. / TITLE OF TOPIC / PREPARATION AND EVALUATION OF POROUS PELLETS LOADED WITH ANTI-ARRHYTHMIC DRUG FOR CONTROLLED RELEASE.
6. / BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study /
ENCLOSURE - I
ENCLOSURE - II
ENCLOSURE – III
7.
/
MATERIALS AND METHODS
7.1 Source of data
7.2 Method of collection of data
7.3Does studies require any investigations or interventions to be conducted on patients or other human or animal? If so, please describe briefly.
7.4 Has ethical clearance been obtained from your institution in case of 7.3
/ ENCLOSURE - IVENCLOSURE - V
ENCLOSURE - VI
ENCLOSURE – VI
8. / LIST OF REFERENCES / ENCLOSURE – VII
9. / SIGNATURE OF CANDIDATE / (VEENA.M.C)
10. / REMARKS OF GUIDE / RECOMMENDED
11. / NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
11.6 Signature / Dr.S.K.SENTHIL KUMAR., M.Pharm, Ph.D,
PROFESSSOR AND HEAD,
DEPARTMENT OF PHARMACEUTICS,
BHARATHI COLLEGE OF PHARMACY,
BHARATHINAGARA, MANDYA,
KARNATAKA- 571422.
Not applicable.
Not applicable.
Dr.S.K.SENTHIL KUMAR., M.Pharm., PhD.
PROFESSOR AND HEAD,
DEPARTMENT OF PHARMACEUTICS,
BHARATHI COLLEGE OF PHARMACY,
BHARATHI NAGARA, MANDYA,
KARNATAKA-571422.
12.1 Remarks of the
Chairman and Principal
12.2 Name and designation of principal
12.3 Signature / RECOMMEDED & FORWARDED
Dr. T. TAMIZH MANI., M.Pharm, Ph.D.
PRINCIPAL,
BHARATHI COLLEGE OF PHARMACY,
BHARATHINAGARA-571422, MANDYA,
KARNATAKA.
6.0
7.0
8.0 / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE – I
6.1 Need for the study
Multi-particulate system such as pellets are often used as oral solid dosage form since they offer therapeutic as well as technological advantages over single unit dosage forms. They disperse freely in the gastro-intestinal tract, contributes to maximum drug absorption, reduced peak plasma fluctuation and less side effects. Furthermore, pellets also allow the formulator to modify the drug release by coating the pellets with different release characteristics can be used to obtain the desired release profile.
Pellets can be defined as small, free flowing ,spherical or semi-spherical solid units,typically from about 0.5 mm to 1.5 mm, and intended usually for oral
The most common advantages of pelletization are
· Improved appearance of the product and the core is pharmaceutically elegant.
· Pelletization offers flexibility in dosage form design and development.
· Pellets are less susceptible to dose dumping.
· It reduces localized concentration of irritative drugs.
· It improves safety and efficacy of a drug.
· Pellets offer reduced variation in gastric emptying rate and transit time.
· Pellets disperse freely in G.I.T. and invariably maximize drug absorption and also reduce peak plasma fluctuation.
· Pellets ensure improved flow properties in formulation development.
Anti-Arrythmic drugs have more side/Adverse effects and also poor Bioavailability. So to increase bioavailability and to minimize side/adverse effects porous pellets for controlled release are prepared. The most important reason for the wide acceptance of multiple unit products is the rapid increase in popularity of oral controlled release dosage forms, Controlled release oral solid dosage forms are usually intended either for delivery of the drug at a specific site within the gastrointestinal tract or to sustain action of drugs over an extended period of time. With pellets, the above mentioned goals can be obtained through the application of coating materials (mainly different polymers), providing the desired function or through the formulation of matrix pellets to provide the desired effect.
ENCLOSURE – II
6.2 Review of the literature
1. Elchidana et al1., Have developed microporous membrane delivery system for indomethacin. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis for more than a decade. This has led to the search for new drug delivery system which can overcome the side effects by controlling the drug release. In this study, pelletization using the method of extrusion/spheronization. The drug containing pellets were further coated to achieve the required release profile as per USP. Coating systems developed on the principle of microporous membrane drug delivery using soluble salt gave the best result.
2. Eskandari et al2.,Have developed an extended release pellet formulation of indomethacin by the centrifugation (rotary fluid bed granulation) or powder layering method. Layered, nonpareil pellets composed of sugar, Avicel pH 101 and lactose were prepared using FREUND CF granulator and were treated by a binder solution(HPC-L) applied by spray gun. A conical designed powder-feeding unit applied the drug powder. Drug content of pellets was determined by HPLC method, Eudragit NE 30 D was used for coating the prepared pellets. The results show that increasing the amount of Eudragit NE 30 D, Opadray and SDS in coating solution adjusts release of the pellets.
3. Sinha et al3., reported four commercial grades of microcrystalline cellulose, Avicel PH 102, Avicel PH 112 and Avicel PH 302 were compared for extrusion spheronization. Model mixes containing Avicel PH 101 with different proportions of fillers like lactose and dicalcium phosphate dehydrate (DCPD) were also compared to observe the influence of these fillers on the pellets properties. The amount of water used for granulation of Avicel/ Avicel mixes was kept constant so as to evaluate and quantitate the influence of these excipents/fillers on the pellet properties. The various pellet properties evaluated included, drug release, size and size distribution, shape, density, friability and flow.
4. Steckel et al4., reported chitosan pellets were successfully prepared using the extrusion/spheronization technology. Microcrystalline cellulose was used as additive in concentration from 70% to 0%. The powder mixtures were extruded using water and diluted acetic acid solution in different powder to liquid ratios. The effect on bead formation using water and different acetic acid concentration and solution quantities were analyzed.
5. Nattawut et al5., studied the influence of the chitosan with different molecular weights, on properties of pellets prepared by extrusion/spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dehydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as a granulating agent. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 405 wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan(60% wt/wt), MCC(17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pellet forming ability.
6. Ishtiaq Ahmed et al 6., investigated the effect of Ammonio Methacrylate Copolymer Dispersion Type A (Eudragit RL 30 D) and Ammonio Methacrylate Copolymer Dispersion Type B (Eudragit RS 30 D) combination in different weight ratios on the release kinetics of Ambroxol Hydrochloride from coated pellets. Microcrystalline cellulose, lactose, maize starch, hydroxypropyl methylcellulose and the drug was incorporated in the nuclei prepared by Extrusion-spheronization technique which was coated with Eudragit RL 30D and Eudragit RS 30D in 1:1,1:1.5,1:2,1:2.5 and 1:3 ratios.. Drug release decreased with increasing amount of Eudragit RS 30D in all cases.
7. Peter Klienebudde et al 7.,investigated the influence of the degree of polymerization (DP) of cellulose materials [microcrystalline cellulose (MCC) and powder cellulose (PC)] on the behavior of these materials during homogenization and extrusion/spheronization processes. Suspensions of the cellulose types with different DP values were homogenized using a high-pressure homogenizer. The particle size, agglomeration index, and apparent viscosity of these suspensions were determined at different times after pouring.
8. Nisar-Ur-Rahman et al8., formulated a release controlling film coat around diltiazem pellets with Eudrgit NE40 and the effects of percent drug layering, PH and stirring speed of dissolution media on drug release were also evaluated. Diltiazem HCL aqueous solutions were applied onto inert pellets to produce drug pellets, which were subsequently coated with aqueous polymer dispersion using bottom spray Fluidized-bed coated pellets was found to be inversely proportion to the thickness of the polymer coat and desirable controlled release characteristics could be achieved by manipulating the coating levels. The percentage drug layering onto inert pellets had no effects on the release rate coated pellets.
9. Jakob Kristensen et al9 (March 2005) The aim of the present study was to investigate the use of different grades of microcrystalline cellulose (MCC) and lactose in a direct pelletization process in a rotary processor. For this purpose, a mixed 2- and 3-level factorial study was performed to determine the influence of the particle size of microcrystalline cellulose (MCC) (~60 and 105 μ m) and lactose (~30, 40, and 55 μ m), as well as MCC type (Avicel and Emcocel) on the pelletization process and the physical properties of the prepared pellets. A 1:4 mixture of MCC and lactose was applied, and granulation liquid was added until a 0.45 Nm increase in the torque of the friction plate was reached. All combinations of the 3 factors resulted in spherical pellets of a high physical strength. The particle size of MCC was found to have no marked effect on the amount of water required for agglomerate growth or on the size of the resulting pellets. An increasing particle size of lactose gave rise to more spherical pellets of a more narrow size distribution as well as higher yields.
The MCC type was found to affect both the release of the model drug from the prepared pellets and the size distribution. Generally, the determined influence of the investigated factors was small, and direct pelletization in a rotary processor was found to be a robust process, insensitive to variations in the particle size and type of MCC and the particle size of lactose.
ENCLOSURE – III
6.3 Objectives of the study
1. To select Anti-arrhythmic drug and suitable polymers for designing controlled release drug delivery system by Extrusion- Spheronization method.
2. To carry out the Preformulation studies.
3. To characterize the prepared pellets for micromeritic properties.
4. To study polymer drug compatibility by FTIR, DSC and Surface morphology by SEM.
5. To carry out drug loading of prepared porous pellets.
6. To carry out the in vitro release studies for the prepared formulation and compared with commercially available oral formulation.
7. To carry out the stability studies for the optimized formulation.
MATERIALS AND METHODS
Drug : Anti-arrhythmic drug like Propofenone Hcl, Procainamide, flecainide, propranolol,
Amiodarone etc
Materials :
· Polymers: Avicel PH 101, HPMC, MCC, etc
· Fillers: Lactose, MCC, Starch, Sucrose etc
· Lubricant: Magnesium stearate, Calcium stearate, Glycerin etc
· Pore forming agent: Sodium chloride etc
· Separating agent: Talc, Kaolin, Silicon dioxide etc
· Glidant: Talc, Magnesium stearate, Starch
Methods
Porous pellets were prepared by extrusion/spheronization method.
Evaluation
1. Drug content measurements.
2. Drug loading and encapsulation efficiency
3. In-vitro release
4. Stability studies
ENCLOSURE-IV
7.1 Source of data
¨ Library: Bharathi college of pharmacy
¨ E-library: Bharathi college of pharmacy
¨ Practical data’s are obtained from laboratory-based studies.
ENCLOSURE-V
7.2 Method of collection of data
The data required for the study would be collected from the literature survey
1. PREFORMUATION STUDIES:
Solubility, M.P, Compatibility of drug with other excipients
2. PREPARATION OF PELLETS:
· Extrusion or spheronisation
· Powder layering
· Solution/ Suspension layering. etc
Any one of the above method is used.
Characterization
1.Particle size analysis
2.Micromeritic properties
3.Friability, Hausner ratio and granule density
4.Surface roughness
5.SEM and Sphericity
6.DSC and FT-IR
7.Pellet Porosity and pore size distribution
8.Internal pore structure
9.X-ray diffraction
10.Loose surface crystal study
Evaluation
1. Drug content measurements.
2. Drug loading and encapsulation efficiency
3. In-vitro release
4. Stability studies
ENCLOSURE-VI
7.3. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
-NOT APPLICABLE-
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE – VII
LIST OF REFERENCES
1. Eskandari.S, Varshosaz.J ,Akhlatavanfarid.G and Hafizi.G, Formulation and in-vitro characterization of extended release pellets of indomethacin using powder-layering technique. Res Pharma Sci,2007; 2(2):65-75.
2. Elchidana.P.A, Deshpande.S.G. Microporous membrane drug delivary for indomethcin. J.Controlled release, 1999,59:279-285.
3. Sinha.V.R, Agarwal.M.K and Kumaria.R. Influence of formulation and excipient variables on the Pellet Properties Prepared by Extrusion Spheronization. Current.Drug.Del, 2005,2: 1-8
4. Steckel.H, Mindermann-Nogly.F. Production of chitosan pellets by Extrusion/Spheronisation. Eur.J.Pharm.Biopharm.2004,57: 107-114.
5. Charoenthai.N, Klienbudde.P. And Puttpipatkhachorn.S. Influence of Chitosan Type on the properties of Extruded Pellets with low amount of Microcrystalline cellulose. AAPS PharmSciTech 2007,8(3),99-109.
6. Ahmed.I,Amin Roni.M, Kibria G. In-vitro release kinetics of Ambroxol Hydrochloride Pellets Developed by Extrusion Spheronisation technique followed by Acrylic Polymer coating. Dhaka Univ. J. Pharm. Sci. 2008,7(1):75-81.
7. Klienebudde.P, Jumma.M and Saleh.F. Influence of degree of polymerization on Behavior of Cellulose during Homogenization and Extrusion/Spheronization. AAPS PharmSci;2000, 2(2).18-27.
8. Sandler.N, Rantanen.J, Romer.M, Marvola.M and Ylisuusi.J. Pellet Manufacturing by Extrusion-Spheronization Using Process Analytical Technology. AAPS PharmaSciTech 2000,6(2).174-183.
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