Download Enclosure-II

FORMULATION AND EVALUATION OF PERINDOPRIL
ERBUMINE PRONIOSOMAL GEL
M.Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka.
Bangalore.
By
KUTE ASHISH JANKIRAM
B. Pharm.
Under the Guidance of
PRAKASH S. GOUDANAVAR
M. Pharm
DEPARTMENT OF PHARMACEUTICS
N.E.T. PHARMACY COLLEGE,
RAICHUR
2010
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
KUTE ASHISH JANKIRAM
1
Name of candidate and address
AT.POST: DUSARBID, BEHIND
(In Block Letters)
POST OFFICE, TQ-SINDHKHED
RAJA, DI-BULDHANA.
2
Name of the Institute
N.E.T.PHARMACY COLLEGE,
RAICHUR.
3
Course of study and subject:
M.PHARM. PHARMACEUTICS.
4
Date of admission of course:
5
Title of the topic:
“FORMULATION AND EVALUATION OF PERINDOPRIL ERBUMINE
PRONIOSOMAL GEL”
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Brief Resume of this intended work:
6.1 Need for the study
6.2 Review of Literature
6.3 Objectives of study
25-06-2010
Enclosure-I
Enclosure-II
Enclosure-III
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Materials and Methods:
7.1 Source of data
Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on
patients of humans or animals? If so, please describe briefly.
---------NO--------7.4 Has ethical clearance been obtained from your institution in case of 7.3?
----------NA-----------
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List of References
Enclosure-VI
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9
Signature of the candidate
10
Remarks of the Guide
The proposed work can be carried out in the
laboratory.
11
Name and designation of
(in block letters)
11.1 Guide
PRAKASH. S. GOUDANAVAR
Assistant Professor
Dept. of Pharmaceutics,
N.E.T. Pharmacy college,
RAICHUR- 584103.
11.2 Signature
11.3 Co-Guide (if any)
------------
11.4 Signature
------------
11.5 Head of Department
Dr. H. DODDAYYA
Professor
Dept. of pharmaceutics,
N.E.T. Pharmacy college,
RAICHUR- 584103.
11.6 Signature
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12.1 Remarks of the
Chairman and Principal
Dr. H. DODDAYYA
Principal,
N. E. T. Pharmacy College,
RAICHUR-584103.
12.2 Signature
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Enclosure-I
6) Brief resume of the intended work.
6.1) Need for the study:
Proniosomes are dry formulation of water-soluble carrier particles that are
coated with surfactant and can be measured out as needed and dehydrated to form
niosomal dispersion immediately before use on brief agitation in hot aqueous media
within minutes1.Proniosomes offer a versatile vesicle drug delivery concept with
potential for delivery of drugs via transdermal route. This would be possible if
proniosomes form niosomes upon hydration with water from skin following topical
application under occlusive conditions2.
Proniosomes minimizes problems of niosomes physical stability such as
aggregation, fusion and leaking and provide additional convenience in transportation,
storage and dosing3. Transdermal therapeutic system has generated an interest as this
system provides the considerable advantage of a non-invasive parentral route for drug
therapy, avoidance of first pass gut and hepatic metabolism, decreased side effects
and relative ease of drug input termination in problematic cases4.
Colloidal particulate carriers such as liposomes5 or niosomes6 have been
widely employed in drug delivery systems and producing them from proniosomes
provides them a distinctive advantage. These carriers can act as drug reservoirs and
the rate of drug release can be controlled by modification of their composition. These
lipid vesicles can carry both hydrophilic drugs (by encapsulation) and hydrophobic
drugs (in lipid domain). Due of their capability to carry a variety of drugs, these lipid
vesicles have been extensively used in various drug delivery systems7 like drug
targeting8 controlled release9 and permeation enhancement of drug 10,
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Perindopril Erbumine (Perindopril tert-butylamine) is an ACE inhibitor, used
in the treatment of hypertension and congestive heart faiure, perindopril is converted
in the body into active metabolite perindroprilate, ACE inhibition is reported to occur
within 1 hour of dose, to be maintained for 24 hours. Perindropril is given by mouth
as the erbumine salt and should be taken before food. In treatment of hypertension
perinndopril Erubumine is given in an intial dose of 4 mg once daily, having
biological half life 1-3 hrs plasma protein binding of about 60%, with peak plasma
concentration occurring in 0.9-1.9hrs11. Perindopril erbumine shows 65-75%
bioavailability but presence of food reduces the conversion of perindopril to the
perindoprilate. According to a previous research, the oxidation rate of Perindopril
erbumine in dermal homogenate is significantly lower than the intestinal homogenate
because the oxidative product of Perindopril erbumine a perindoprilate shows poor
absorption from the intestine12. Perindopril erbumine when administered initially
causes hypotension, which can prove to be harmful in diuretic treated- and congestive
heart failure patients. Persistent hypotension may cause some trouble in myocardial
infarction patients13. Therefore, the use of transdermal drug delivery system can
reduce the side effects associated with Perindopril erbumine. Niosome carriers, well
known for their potential in topical drug delivery, have been used to transport
perindopril erbumine molecule in the skin layer.
Enclosure-II
6.2) Review of literature:
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1. Satyabrata B et al., prepared mucoadhesive buccal tablets of perindopril using
polyethylene oxide and carnauba wax by direct compression technique. The
prepared tablets were sintered at various temperatures like 600C and 700C for
1.5 hr and 3 hr. The best in-vitro drug release profile was achieved with the
formulation F4A (sintered at 600C for 1.5 hr) which contains the drug,
polyethylene oxide and carnauba wax in the ratio of 1:15:10. Formulation F4A
containing 4 mg of perindopril exhibited 8 hrs sustained drug release (98%)
with desired therapeutic concentration14.
2. Alsarra IA et al., prepared ketorolac proniosomes across excised rabbit skin
from various proniosome gel formulations was investigated using franz
diffusion cells. Proniosomes prepared with Span 60 provided a higher
ketorolac flux across the skin than did those prepared with Tween 20 (7- and
4-fold the control, respectively). Each of the prepared niosomes achieved
about 99% drug encapsulation15.
3. Chandra A et al., formulated piroxicam proniosomes using surfactant,
cholesterol and lecithin. The results revealed that span 60 based lecithin
vesicles (S6L) showed significant (p<0.05) reduction in paw swelling. The
percent inhibition was found to be more than that of piroxicam carbopol gel. It
is probable that there is enhanced drug delivery from lipid vesicles. The short
fall seen with maltodextrin and sorbitol based formulations account for the
slow release observed in in-vitro studies16.
4. Solanki AB et al., developed ketoprofen proniosomes for transdermal
delivery. The niosomes were prepared using a slurry method followed by in
vitro evaluation after embedding the proniosomes-derived niosomes into a
carbopol matrix. Niosomal gel containing ketoprofen could perform
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therapeutically better effects than the conventional formulations which may
lead to improved efficiency and better patient compliance.17.
5. Gupta A et al., designed captopril proniosomal transdermal drug delivery
system using sorbitan fatty acid esters, cholesterol, lecithin by coacervationphase separation method. The method of proniosome loading resulted in an
encapsulation yield of 66.7-78.7%. Proniosomal gel possesses high
entrapment efficiency and utilizes alcohol, which itself can act as a penetration
enhancer. At refrigerated conditions, higher drug retention was observed18.
6. Chandra RJ et al., prepared maltodextrin based proniosomes loaded with
aceclofenac by slurry method with different surfactant to cholesterol ratio. The
formulation F4 (surfactant: cholesterol 150:100) which showed higher
entrapment efficiency of 83.24 ± 1.34 and in-vitro releases of 97.122% at the
end of 24 hours was found to be best among the all 7 formulation. Release was
best explained by the zero order kinetics19.
Enclosure-III
6.3) Objectives of the study:
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The present study is planned with the following objectives:
1. To prepare perindopril erbumine pronoisomal gel using various
surfactants.
2. To study drug surfactants interaction by using DSC and FT-IR
instruments.
3. To characterize the formulations for various physicochemical parameters.
4. To evaluate the tablets for in vitro dissolution studies.
5. To carry out stability studies for selected formulations as per ICH
guidelines.
Enclosure-IV
7) Materials and Methods:
7.1) Source of data:
Primary data: This data will be collected by conducting laboratory experiment
and recording the observation.
Secondary data: This will be collected from various journals and text books.
Enclosure-V
7.2) Method of collection of data:
The data for the study is planned to collect from the laboratory-based
experiments:
1. Preformulation studies like solubility, melting point and characterization of the
drug and surfactants will be done by employing suitable methods and
compatibility of drug with surfactants will be carried out by using Infra-Red
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Spectroscopy and Differential Scanning Calorimetry instruments adopting
reported methods.
2. Pronoisomal Gel of Perindopril Erbumine is prepared by using Soya lecithin,
cholesterol, Span 20, 40, 60, 80 and tween 20,40,60,80.
3. The prepared gel will be evaluated for Vesicle Size Analysis, Rate of
Spontaneity, Encapsulation Efficiency, In Vitro Release, and Stability Studies.
4. In vitro release studies will be carried out by using dissolution test apparatus
USP XXIV and the drug release data will be subjected to various kinetics
models.
5. For selected formulations stability studies will be carried out using stability
chamber as per ICH guidelines.
Enclosure- VI
References:
1. Solanki AB, Parikh JR and Parikh RH
Formulation and optimization of
Piroxicam proniosomes by 3-Factor, 3-Level Box-Behnken Design. AAPS
Pharm. Sci. Tech., 2007; 8(4); E1-E7.
2. Fang JY, Yu SY, Wu PC, Huang YB, Tsai YH. In-vitroskin permeation of
estradiol from various proniosomes formulation. Int J Pharm 2001; 215:91-99.
3. Hu C, Rhodes DG. Proniosomes: A Novel Drug Carrier Preparation. Int J
Pharm 1999; 185(1): 23-35.
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4. Wu PC, Huang YB, Chang JJF, Chang JS, Tsai YH. Evaluation of
pharmacokinetics and pharmacodynamics of captopril from transdermal
hydrophilic gel in normotensive rabbit and spontaneously hypertensive rats.
Int J Pharm2000; 209: 87-94.
5. Biju SS, Talegaonkar S, Misra P.R, Khar R. K. Vesicular systems: An
overview. Indian J. Pharm.Sci. (2006); 68:141-153.
6. Shahiwala, A, Misra, A. Studies in topical application of niosomally entrapped
nimesulide. J. Pharm. Sci. 2002; 5(3):220-225.
7. Puglia C, Trombetta D, Venuti V, Saija A,Bonina F (2004). Evaluation of in
vivo
topicalanti-inflammatory activity of indometacin from liposomal
vesicles. J. Pharm. Pharmacol. 56 : 1225-1232
8. Gupta PN, Mishra V, Singh P, Rawat A, Dubey P, Mahor S, Vyas SP. Tetanus
toxoidloaded transfersomes for topical immunization. J. Pharm.Pharmacol.
2005; 57: 295-301.
9. Barber R, Shek P. In: Pharmaceutical Particulate Carriers. 1993; 1–20
10. Verma DD, Verma S, Blume G, Fahr A. Liposomes increase skin Penetration
of entrapped and non-entrapped hydrophilic substances into human skin: a
skin penetration and confocal laser scanning microscopy study. Eur. J. Pharm.
Biopharm. 2003; 55: 271-277.
11. Martindale. The complete drug reference. 34th Ed. Pharmaceutical Press, Great
Britain 2005; 980-81.
12. Zhou XH, Li Wan PA. Stability and in-vitro absorption of captopril, enalapril
and lisinopril across the rat intestine. Biochem Pharmacol 1994; 47: 11211126.
13. Tripathi KD. Essentials of Medical Pharmacology. NewDelhi, India, Jaypee
Brothers, 2003 pp 449-454.
14. Bhanja S., Ellaiah P., Mohanty C., Murthy K.V.R., Panigrahi B., Padhy S. K.
Design and in vitro Evaluation of Mucoadhesive Buccal T ablets
of
Perindopril Prepared by Sintering Technique. Int J PharmTech Res. 2010;
2(3):1810-1823.
15. Alsarra I. A., Bosela A.A., Ahmed S.M., Mahrous G.M. Proniosomes as a
drug carrier for transdermal delivery of ketorolac. Eur J Pharm and Bio 2005;
59: 485–490.
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16. Chandra A. and Sharma P. K. Proniosome based drug delivery system of
piroxicam. African J Pharm and Ph.cology 2008; 2(9):184-190.
17. Solanki A.B., Parikh J.R., Parikh R.H. Preparation, Optimization and
Characterization of Ketoprofen Proniosomes for Transdermal Delivery. Int J
PharmSci and Nanotechnology 2009; 2(1):413-420.
18. Gupta A., Prajapati S.K., Balamurugan M., Singh M.,Bhatia D. Design and
Development of a Proniosomal Transdermal Drug Delivery System for
Captopril Tropical J Pharm. Res. 2007;6(2): 687-693.
19. Chandra A. and Sharma P. K. Proniosome based drug delivery system of
piroxicam. African J Pharm and Ph.cology 2008; 2(9):184-190.ss
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