joural club on in situ gel

1. Journal club
Rushikesh .V. Lavhate
Guide: Dr.Rohan Barse.
2nd year M pharmacy.
Yashwantrao bhonsale college of pharmacy,sawantwadi
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2. FORMULATION AND EVALUTION OF
MOXIFLOXACIN IN SITU GEL
Source: Journal of Oral Biology and Craniofacial Research
(journal homepage:
https://www.sciencedirect.com/science/article/abs/pii/S2212426818302823?via%3Di
hub )
Author: Ganesh P. Swain, Shivani Patel, Jaimini Gandhi, Pranav Shah
Department of Pharmaceutics, Maliba Pharmacy College , surat
Objective:
 In-situ gel provides the drug release at a controlled rate.
 In situ gel reduces side effects, thus improving patient compliance
 Drug sustained release effect and access deeper areas.
 Reduce the bacterial flora, lessen inflammation and to discontinue bone desorption.
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3. Points to be discussed….
Abstract
Introduction
Material
Method of preparation
Result
Discussion
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4. ABSTRACT:
Periodontitis is a chronic inflammatory disease affecting supporting tissues of teeth . Conventional treatment
is the systemic administration of antibiotics which requires repeated dosing and resulted in toxic adverse
effects. These consequences can be solved by delivering the drug at the desired target site to show local
therapeutic action. In situ gel-forming systems are polymeric system that exists as flowing solution before
administration and undergoes phase transition to form a gel in a physiologic environment. Aim of the present
work was to formulate and evaluate an in situ gelling drug delivery system of moxifloxacin by cold method
and hot method using the polymers poloxamer 407 and gellan gum .
The prepared in situ gels were evaluated for visual in spection, surface pH, viscosity,
syringeability, gelation temperature, gelling time, in vitro gelling capacity, drug content and in vitro drug
release. The formulation F5 was selected as the optimized formulation which has a gelation temperature of
.33±0.57◦C with drug release at 98 % 9 hrs. It follows first order release kinetics with Higuchi model 𝑑rug
release mechanism. The selected formulation was evaluated for its antibacterial activity. 4

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INTRODUCTION:
Periodontal diseases are one of the most prevalent oral diseases,
where 80% of American adults and more than 50% of Indian center of population suffers
from this chronic inflammatory disease which demonstrates the harshness of the disease.
The cause of periodontal diseases are usually gram negative, facultative anaerobic bacteria
species like B. intermedius and B. gingivalis; fusiform organisms: Actinobacillus,
actinomycetemcomitans, Wolinella recta and Eikenellaspp, various bacilli and cocci;
spirochetes; amoebas and trichomonas.
API loaded formulations at a specific site in the body by bio-adhesive
water soluble polymers for controlled delivery of biologically active agents systemically or
locally. Biodegradable excipients have been used in drug delivery system. Than the
exploitation of bioabsorbable delivery approach represents a key pace ahead in the
management of periodontal diseases. Moxifloxacin binds to in addition by inhibit the
bacterial enzymes DNA gyrase (topoisomerase II) and topoisomerase IV, resulting in
inhibition of DNA replication, repair and cell death in sensitive bacterial species.
Poloxamer 407 is a PEO-PPO-PEO triblock copolymer thermo- responsive polymer and it
forms gel as soon as the temperature reaches to the body temperature. Gellan gum is a
natural polysaccharide which consists of double helical segments and these segments
assemble and forms in-situ gel in presence of monovalent or divalent cations. Divalent
cations are there in oral cavity which interacts to form gel.

6. MATERIAL & METHODS :
Materials:
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Moxifloxacin hydrochloride Mankind Pharma, Ahmedabad (India).
Gelllan gum S.D Fine Chem Limited, Mumbai (India).
Poloxamer Yarrow Chem Products, Mumbai (India).
Methyl paraben
Research-Lab Fine Chem Industries, Mumbai,
(India).
Propyl paraben
Research-Lab Fine Chem Industries, Mumbai,
(India).
Triethanoloamine
S.D Fine Chem Limited, Mumbai , (India).
Disodium edetate Suvidhinath Laboratories, Vadodara ,(India).
Deionized water Lemon water Co Pvt. Ltd, Surat, (India).

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Method of preparation :
Preparation of Smart Gel
Periodontal Drug Delivery
System (SGPDDS) by hot
process
Preparation of smart gel
periodontal drug delivary
system( SGPDDS by cold
process

8.  Hot process :
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Polymeric solution of gellan gum was prepared by dispersing the
polymer in deionized water.Polymeric solution was heated between 60-
90°C with constant stirring using a magnetic stirrer with hot plate to
assist the hydration of gelling agent. The necessary amounts of
preservatives (methyl paraben, propyl paraben) and sodium citrate were
added to it with continuous stirring. The solution was cooled below
40°C. Finally, Moxifloxacin Hydrochloride was added into this
polymeric solution.

9.  Cold process :
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Polymeric solution of poloxamer 407 was prepared by dispersing the polymer
in deionized water at 4°C by using magnetic stirrer. The partially dissolved
polymer was stored in refrigerator for 24 hours until the entire polymer was
completely dissolved. The required amounts of preservatives ( methylparaben,
propyl paraben) were added with stirring. Finally, Moxifloxacin
Hydrochloride was added to the polymeric solution.

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Evalution parameters :
o FTIR Spectroscopy
o Physical appearance
o Determination of ph
o Syringeability
o Measurement of viscosity
o Drug content
o Gelation temperature
o Gelling time

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• FTIR Spectroscopy of drug :
All the prominent peaks of reference drug were present in the IR spectra of sample drug. Hence, the
results of FTIR analysis confirms that Moxifloxacin Hydrochloride (sample) was pure and could be
used for further study.
All the prominent peak of drug and excipients were present in the IR spectra of mixture indicating
physical compatibility between drug and excipients. Four peaks at 3529 cm-1 (secondary N-H
stretching), 1707.41 cm-1 (CO stretching of keto group), 1456.51 cm-1 (OH bending of COOH) and
1623.45 cm-1 (CO stretching) were found in FTIR spectra of Moxifloxacin Hydrochloride while
3524.01, 1706.57, 1445.17, 1601 cm-1 were observed in mixture. This indicates that the characteristic
peaks of the drug were retained in the mixture. Hence, there was no interaction found between the drug
and the excipients.
RESULT AND DISCUSSION:

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• Full Factorial Design :
Preliminary investigations of the process parameters exposed that factors such as concentration of
poloxamer 407 (X1) and gellan gum (X2) exhibited significant influence on gelation temperature,
gelling time, drug release at 9 hr and time required to release 90% of drug.
Run Conc. of poloxamer
(%w/v)X1
Conc. of
gellan
gum
(%w/v)
X2
Gelation
temperature
(˚C)
Y1
Gelling time
(sec) Y2
Drug release at
1hour (%)
Y3
Time required
to release 90%
of drug
(hrs) Y4
1 18 0.1 42±0.5 176±2.516 33.386±0.319 5.8±0.208
2 19 0.1 40±0.5 168±2.516 37.993±0.204 6.4±0.118
3 20 0.1 39±0.5 151±2.516 25.510±0.315 6.7±0.212
4 18 0.2 40±0.5 137±2.000 29.724±0.192 7.7±0.154
5 19 0.2 38±0.5 124±3.605 56.528±0.214 8.3±0.289
6 20 0.2 37±0.5 104±2.081 24.432±0.316 8.7±0.263
7 18 0.3 36±0.5 88±1.527 26.544±0.177 9.1±0.285
8 19 0.3 35±0.5 71±1.527 23.325±0.177 10.2±0.154
9 20 0.3 34±0.5 51±1.527 20.491±0.315 11.2±0.163

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• Release kinetics of optimized batch :
Optimized
batch
Zero
order
First
order
Hixon
Crowell
Higuchi Korsemeyer Peppas
R2 R2 R2 R2 R2
0.9967 0.9762 0.873 0.9617 0.9685

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Anti bacterial
study : studies were carried out to assess the performance
of MX loaded in-situ gel. The results of
antimicrobial activity were shown in table 8 and
figure 8. The study indicated that MX retained its
antimicrobial activity when formulated as gel
forming system for periodontal system against
selected S. aureus and E.coli. Difference in the
zone of inhibition in vehicle and medicated in-situ
gels obtained from the in-vitro antimicrobial study
indicated that the formulation contains active drug
moiety.

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Rough appearance of liquid gels could be attributed to Pl407 as it is present
in large amount showed the SEM images of freeze dried batch at different
magnifications 2, 5 and 10 KX which exhibited cracks, pits, lumps formed
due to loss of water during drying process concluding towards large water
content of gel andsupporting their hydrogel nature and it also showed
porosity.
SEM STUDY :

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CONCLUSION:
Moxifloxacin Hydrochloride loaded thermosensitive smart gel was successfully formulated
by combination of poloxamer 407 and gellan gum. FTIR study indicates no sign of
incompatibility between drug and excipient. So the selected polymers were likely to be
proper for the preparation of periodontal smart gel. The formulations remain in liquid at
non- physiologic conditions (10-25˚C) and forms gel at physiologic condition (37˚C).
The developed formulations showed acceptable results for gelation
temperature, gelling time, syringeability and drug release which were dependent on
concentrations of poloxamer 407 and gellan gum. Amongst the various formulations (F1-
F9) assorted, optimized batch contains 19.072 %w/v poloxamer 407 and 0.245%w/v gellan
gum, which have desired gel temperature 36˚C, gelling time 102 sec, 98 % of drug release
at 9 hr.

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REFERENCE :
1.Borderwala K, Patel S, Gandhi J, Naik H, Pillai L, Shah P. Advanced local drug delivery approaches for
periodontitis: A strategic intervention. Research and Reviews: A journal of Pharmaceutical Sciences 2008; 9:4-11
2. Jain N, Jain GK, Javed S, Iqbal Z, Talegaonkar S, Ahmad FJ. Recent approaches for the treatment of
periodontitis. Drug Discovery Today 2008; 13:932-943
3. Joshi D,Garg T, Goyal AK, Rath G. Advanced drug delivery approaches against periodontitis. Drug Delivery
2016; 23:363-377.
4. Bansal M, Mittal N, Yadav SK, Khan G, Gupta P, Mishra B. 2017. Periodontal thermoresponsive,
mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro
characterization and antimicrobial study. Journal of Oral Biology and Craniofacial Research 2017; 5:2-12.
5. Dabhi MR, NagoriSA,Gohel MC, Parikh RK, Sheth NR. Formulation development of smart gel periodontal
drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug
Delivery 2010; 17:520-531.
6. Garala K, Joshi P, Shah M, Ramkishan A, Patel J. Formulation and evaluation of periodontal in situ gel.
International Journal of Pharmaceutical Investigation 1013; 3:29- 31

18. THANK YOU.
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