Download formulation and evaluation of anti microbial suppositories

FORMLULATION AND EVALUATION OF
ANTI-AMOEBIC SUPPOSITORIES
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
B.NAGA VAIDYANATHA REDDY
I M.PHARM
UNDER THE GUIDANCE OF
Dr. K .RAMESH
PROFESSOR, HEAD OF THE DEPARTMENT
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
BANGALORE-560064
(2011-2012)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1
Name of the Candidate and Address
B.NAGA VAIDYANATHA REDDY
KARNATAKA COLLEGE OF PHARMACY
# 33/2 THIRUMENAHALLI
HEGDE NAGAR MAIN ROAD
BANGALORE-560064.
PERMANENT ADDRESS:
S/0: B.SIVABALI REDDY,
H.NO-25-645, SRINIVASANAGAR,
NANDYAL
Dist: KURNOOL,
State: ANDRAPRADESH-518002
2
KARNATAKA COLLEGE OF PHARMACY
Name of the Institution
# 33/2 THIRUMENAHALLI
HEGDE NAGAR MAIN ROAD
BANGALORE-560064.
3
Course of the Study and Subject
MASTER OF PHARMACY
(PHARMACEUTICS)
4
Date of Admission
5
Title of the Topic
FORMULATION AND EVALUATION OF ANTI –AMOEBIC SUPPOSITORIES
8thJULY 2011
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6.
Brief Resume of the Intended Work:
6.1 Need for the study
The rectal route of drug delivery have been recognized as an alternative to the oral
route in situations such as when the patient is comatose, unable to swallow or when the
drug produces nausea or vomiting. There are several therapeutic reasons why a drug should
be administered rectally than orally. One of these is that, it is possible to avoid partly
hepatic first pass elimination following rectal administration.
The rectal venous drainage is such that the upper part is connected with the portal
system and the lower part directly with the systemic circulation. However there is no sharp
distinction between these drainages, since the rectal veins are linked by an extensive
anastomoses network. It has been accepted that atleast 50-70% of a drug suitable for rectal
administration is absorbed via the above direct pathway. It is well recognized that drug
absorption after rectal administration is in agreement to a considerable extent with the pH
partition theory. In the light of this, efforts have been made in recent times to present a
good number of drugs in suppository form.
Rectal administration of anti-amoebic is accepted as effective prophylaxis against
infection associated with surgery and as treatment of established infection. Since
observation of the therapeutic effect is known to be faster by the rectal route of
administration and overcomes the gastric irritation problems rectal suppositories were
deemed as appropriate.
Anti-amoebic in the form of rectal therapy for localized action is readily achieved
and it may be feasible for rectal therapy to overcome the limitations and to realize its
potential advantages.
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6.2 Review of the literature:
Nitroimidazole resistant vaginal trichomoniasis treated with intravaginal
paromomycin (50mg) and trichomoniasis but resulted in severe local side effects.
Paromomycin useful for different cases of nitroimidazole resistance tricomonas vaginalis
vaginitis to exact dose findout.1
The bioavailability of drugs from suppositories is taken into consideration. The
factors affecting bioavailability, the avoidance of first-pass effects, the role of absorption
promoters, a sustained-release effect and selected therapeutic indications for the application
of suppose.2
Volumetric methods were used to metronidazole with calf thymus DNA
determined binding constant (k) binding site size (s). This method interaction of
metronidazole with surface-conform DNA and peak current of metronidazole at the
biosensor for metronidazole determination. This method applied with high precision and
accuracy compared with spectroscopic methods for estimation of the total metronidazole
drug content in pharmaceutical dosage forms.3
Antibacterial metronidazole used in most common therapy in the treatment of
bacterial vaginosis (B.V.) this are different formulation is available creams, gels, vaginal
lavages and vaginal suppositories. The aim to realize vaginal mucoadhesive tablets by
including bio adhesive polymer as chitosan (FG90C), polyvinyl pyrrolidone (PVPK90)
poly carbophill (pcppa) the characterized by studies of DSC, friability, hardness,
mucoadhesion in vitro release and antibacterial activity. The polymers FG90C and PVPK90
(1:1 ratio) suitable formulating of metrodinazole traditional dosage forms for vaginal
topical administration of in vitro bacterial inhibitor studies by using diffusion method.4
The physical and release properties of metronidazole suppositories are influenced
by the bases and adjuvants employed. Tween 80 and sodium salicylate used to formulate
only immediate-release suppositories while methyl cellulose also used in sustained release
metronidazole suppositories bases are witepsol , polyethylene glycol, PEG 1500, PEG 6000
by using fusion method.5
3
Administration of anti microbial suppositories is accepted as effective prophylaxis
against infection associated with surgery and as treatment of established infection. This
study shows that in gravely ill patients metronidazole administration as suppositories gives
perfectly adequate therapeutic serum concentration of the drug, but that achieve these
concentration rapidly the first suppository should be given with an intravenous loading
dose.6
PEG-metronidazole conjugates with in vitro and in vivo studies carried out by
using metronidazole a drug used for treatment of protozoal infections. By using different
conjugated to linear (or) branched polymers of polyethylene glycol 5000-OH, PEG- 20,000
-OH, Mpeg-10,000 –NHS, Mpeg-20,000-NHS. Finally the MET solubility, stability,
release characterstics, and in vivo studies carried out I.V. &S.C. administration and
pharmacokinetic properties up on conjugation.7
To evaluate the efficacy and tolerability of vaginal pessary treatment of
vaginitis. The method involved in phase-3 studies using one vaginal pessary the reduction
occurred in symptoms and signs of vaginitis the gynecological and microbiological
evaluation carried out, by using microscopy and candida albicons culture. The combination
of metronidazole and miconazole treatment of the most common causes of vaginitis.8
Extensively used beta- lactam antibiotics and 5- nitro imidazole used anaerobic
bacteria antibiotic resistance gram negative bacilli of beta- lactam classified as 1)
production 2) alteration 3) changes in outer membrane permeability. The 5- nitroimidazole
molecule reduction of nitro group in the absence of oxygen the identified in bacteroides
fragilis group spp. The mechanisms of resistance is critical for both the selection of
antimicrobial therapy and the design of new antimicrobial agents. To
review the
mechanisms for and the prevalence of beta-lactam and metronidazole resistance in strain
belonging to the B. fragi.9
The suppositories properties mainly depend the properties of bases.these bases
properties mainly affect the formulation and evaluation of the suppositories.10
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6.3 OBJECTIVE OF THE STUDY:
The objective of the study is as follows:
1) The current study is to develop an ideal rectal drug delivery system.
2) Formulation of suppositories by suitable method.
3) Characterisation of formulated suppositories.
4) Evaluation of suppositories for their physicochemical studies.
5) Stability studies for selected formulations.
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Materials and Methods:
7.1
Source of data:
Review of literature resourced from:
Journal such as
. Indian journal of pharmaceutical sciences
. Journal of controlled release
. Indian drugs
. Science direct
Websites:
. Word Wide Web
.
J-Gate@Helinet.
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, scale-up techniques and stability studies
obtained from ICH guidelines
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7.3
Materials
Anti-amoebic drug and bases will be procured / obtained from pharma grade suitable
manufacturer. All the other reagents will be of analytical grade.
7. 4
Methods
1) Preparation of suppositories by hot melting.
2) Thermal analysis.
3) Evaluation
a) Visual evaluation.
b) Melting point.
c) Liquefaction time
d) Mechanical strength.
e) Solidification.
f)Drug release studies
7.5 Does the study require any investigation or interventions to be conducted on
patients or other humans or animals?
-Does not required-
7.6 Has ethical clearance been obtained from your institution in case of
7.5?
- NO –
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List of References
1. Poppe AJ. Anti microbial-resistant vaginal trichomoniasis treated with
paromomycin. Eur J Obstet Gynecol Reprod Biol. 2001 May 30; 96: 119- 20.
2. Hermann TW. Bioavailability of drugs from suppositories. Int J pharm 1995Jan
30; 123: 1-11.
3. Xiaohua J, Xiangqin L. Voltammetry of the interaction of metronidazole with
DNA its analytical applications. Bio electrochem 2006 Aug 24; 68:206-12.
4. Luana P, Valeria A, Cinzia P, Stefania S, Carlo R. Metronidazole mucoadhesive
tablets for vaginal administration. Int J Pharm 2009 May 18; 377:120-27.
5. Adegboye TA, Ltiola OA. Physical and Release Properties of Metronidazole
Suppositories.Trop J Pharma Res. 2008 march 19; 7(1): 887-96.
6. Barker EM, Aitchison JM, Cridland JS, Baker LW. Rectal administration of
metronidazole in severely patients. Br Med J 1983 July 30; 287: 311-13.
7. Cinzia B, Manuela B, Gianfranco P,
Maria V. Metronidazole –PEG
conjugates in vitro and in vivo properties. IL Farmaco 2005 July 22; 60: 783-8.
8. Fabio P, Aroldo C, Geraldo D, Iara L, Luis B, Alvaro P. Metronidazole and
miconazole nitrate in treatment of vaginitis. Int J Gynaecol obstet 2008 April 10;
102: 287-92.
9. Hong F, Charlotta E, Maria H, Carlerik N. metronidazole resistant Bacteroides
Fragilis group. Int J Antimicrob Agents 2002 Feb 12; 19: 361-70.
10. Lieberman A. Pharmaceutical dosage forms: Edited by Rieger M, Banker S,
Martin, Gilberts. Disperse system. Second ed. New york.Academic Press s2005;
p: 446-96.
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