Download 4 2. LITERATURE REVIEW: Ariyana, et al (2014), developed

2. LITERATURE REVIEW:
Ariyana, et al (2014), developed alginate based metronidazole periodontal gel for
microbes abolition in periodontal pocket. Metronidazole periodontal gel 25% was
prepared using alginate gel alone and in combination with 0.5 and 1% Carbopol. All
of prepared formulations were evaluated. Stability of formulations were studied for 3
months including drug content, color and viscosity. The release of metronidazole
from alginate gel showed sustained release properties. Within 300 minutes study,
metronidazole released from formulations without Carbopol, with 0.5%, and 1%
Carbopol were 40.17%, 47.67%, and 51.48%, respectively. Addition of 0.5 and 1%
Carbopol did not significantly affect the drug release. All formulations showed
excellent inhibition to Staphylococcus aureus. The largest zone of inhibition was
found on formula without Carbopol, then followed by formula with 1% and 0.5%
Carbopol. However, the color was not affected. It is concluded that the alginate based
metronidazole periodontal gel has sustained release properties.19
Nicolas T, et al (2014), designed a biodegradable cellulosic device for periodontal
pockets treatment containing chlorhexidine. Paper points (PPs) were first oxidized to
promote their resorption, then grafted with β-cyclodextrin (CD) or maltodextrin (MD)
in order to achieve sustained delivery. The cytocompatibility of the oxidized– grafted
PP was demonstrated by cell proliferation assays. Finally, the disc diffusion test from
dig-CHX loaded PPO-MD samples immersed in human plasma was developed on
pre-inoculated agar plates with four common periodontal pathogenic strains:
Fusobacterium
nucleatum,
Prevotella
melaninogenica,
Aggregatibacter
actinomycetem comitans and Porphyromonas gingivalis.20
Swaroopa A, et al (2014), formulated microemulsion gel of Satranidazole for the
treatment of periodontitis. The aim was to increase the solubility of Satranidazole, a
lipophilic drug and to enhance depth of penetration of the drug into the periodontal
pocket for efficacious treatment of periodontitis. The formulations were developed
using isopropyl myristate, tween 80, ethanol; oleic acid, tween 80, propylene glycol;
oleic acid, cremophor RH 40, ethanol. Optimization of formulations was done based
on in vitro diffusion studies. The microemulsion was gelled using carbopol 940 as the
gelling agent. The formulations were evaluated for pH, viscosity, percent
transmittance, centrifugation, and characterized by scanning electron microscopy,
particle size, zeta potential and polydispersity index. The formulation inhibited the
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growth of micro organism, Salmonella typhimurium which indicates that the
formulation could be used to treat periodontal infection. 21
Kevin G, et al (2013), formulated in situ gel for the treatment of periodontal disease.
Temperature sensitive in situ gel containing 0.1% w/v Chlorhexidine hydrochloride
was formulated by cold method using different polymers. Initial study was done to
optimize different types and concentration of polymers such as Poloxamer 188,
Poloxamer 407, Gellan gum, and Carbopol 934P. Central composite design was
employed for optimization on responses such as gelation temperature, spreadability,
cumulative percentage release at 2 h, and time for 50% drug release (t 50%). Each
formulations were evaluated The drug release, gelation temperature was considerably
decreased with increasing t50% as the concentration of each polymer was increased.
The formulation F6 showed the highest overall desirability of 0.6283 and, therefore,
this formulation was considered to be the optimized formulation. Additional, all the
formulations showed sustained drug release for a period of 6 h, which satisfied to treat
periodontal disease. 22
Abolfazl A, et al (2013), designed mucoadhesive gel from herbal source for the
treatment of periodontitis. The semisolid concentrated extracts were incorporated in
gel base. Mucoadhesive gels were prepared using carbopol 940‚ sodium
carboxymethylcellulose (sodium CMC) and hydroxypropyl methylcellulose K4M
(HPMC) as bioadhesive polymers. Physicochemical tests‚ mucoadhesive strength
measurement and in vitro drug release study were carried out on two formulations
containing carbopol 940 and sodium CMC polymers (Formulations F4 and F5). We
investigated the antibacterial activity of formulation F5 against Porphyromonas
gingivalis using the disk diffusion method. Physical appearance, homogeneity and
consistency of F4 and F5 were good. Mucoadhesion and viscosity of F5 (1% carbopol
940 and 3% sodium CMC) was more than F4 (0.5% carbopol 940 and 3% sodium
CMC). Drug release from F5 was slower. Both of formulations were syringeable
through 21 G needle. In the disk diffusion method, F5 produced significant growth
inhibition zones against P. gingivalis. 23
Gunjan G, et al (2013), reported local drug delivery systems which includes
sustained and controlled devices such as tetracycline fibres, metronidazole gel,
Minocycline oniment, Chlorhexidine chip and Doxycycline hyclate in a resorable
polymer. 24
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Fouad H, et al (2013), performed a study to develop a biodegradable periodontal chip
containing thymoquinone and chitosan and to evaluate its effectiveness for managing
chronic periodontitis. Overall, 180 periodontal pockets were evaluated. It was
concluded that periodontal chips containing thymoquinone can be used as adjuncts for
the treatment of patients with chronic periodontitis. 25
Tarun P, et al (2013), formulated dental gels for extended period of time. The
ofloxacin gels prepared with different hydrophilic polymers (MC, HPMC, HPC and
HEC) in different concentrations of propylene glycol. Physicochemical studies were
done. In vitro drug release studies were carried out in diffusion cell using pH 7.2
phosphates buffer as receptor medium. Stability studies were carried out for 3 months
at different temperature conditions 25 ± 2oC, 37 ± 2oC, and 4oC. During stability
studies different parameters like pH, spreadability, extrudability, viscosity and drug
content, did not show any noteworthy (p>0.05) deviation. 26
Pratik P, et al (2013), designed sustained release chlorhexidine in situ gel for
periodontitis. In situ mucoadhesive gel of Chlorhexidine gulconate was prepared
using the cold method using Pluronic F 127 and Xanthan gum for their
thermosensitive gelation and mucoadhesive nature, respectively. It was evaluated for
viscosity, gelation temperature, mucoadhesive force, in vitro drug release, pH, drug
content. Drug-excipients compatibility study was done by FTIR. Optimized
formulation had the gelation temperature of 37.2ºC with the mucoadhesive force of
5.18 gm/cm2. It was found that xanthan gum not only showed good quality
mucoadhesion but also amend the drug release from in situ gel. 27
Palak V, et al (2013), developed bioadhesive gel containing Amoxicillin trihydrate
loaded microspheres in order to sustain, localize and target drug action in periodontal
pockets. Amoxicillin trihydrate was loaded in gelatine microspheres using
glutaraldehyde cross linking. The microspheres were evaluated for % yield, % drug
entrapment, particle size, drug release as well as by scanning electron microscopy
(SEM) and Fourier transform infrared spectroscopy (FTIR). % yield, % drug
entrapment and particle size of optimized batch (F8) microspheres were 94.2%,
94.3%, 80.1µm, respectively. The pH, viscosity and bioadhesive strength of
bioadhesive gel was 6.9, 4000cps, 6.5gm, respectively. Sustain release of Amoxicillin
trihydrate over a 6hr period from the microspheres and gel was achieved. 28
Tikshdeep C, et al (2013), developed diclofenac sodium gel. Preformulation studies
was done.
High molecular
weight
water
soluble polymers of Carboxy
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methylcellulose, Carbopol 940 LR, Xanthan gum that possesses very high viscosity,
transparency, film forming properties at low concentration, are used in formulation of
topical gel, along with different penetration enhancers like Oleic acid, Propylene
glycol, and Tween 80. Gel formulations were evaluated. From the study it was
concluded that formulation containing Carbopol 940 LR with Tween 80 showed good
consistency, homogeneity, and spreadability and has wider prospect for topical
preparations as compared to Carboxymethyl cellulose and Xanthan gum. 29
Vicky K, et al (2013), reported a review on local drug delivery systems in the
treatment of periodontitis. Eradication of microorganisms from the periodontal pocket
is the most important step in treating periodontitis. The limitations of mouth rinsing
and irrigation have provoked research for the development of alternative delivery
systems. Recently, advances in delivery technology have resulted in the controlled
release of drugs. This article has discussed the various local drug delivery devices
used in treating periodontitis. 1
Prakash S, et al (2013), developed in situ periodontal gel containing levofloxacin for
the treatment of periodontal disease. Levofloxacin has a conventional dose of about
500 mg per day. Levofloxacin periodontal gel was prepared by different
concentrations of gellan gum, poloxamer 407. All the prepared formulations were
evaluated. By compatibility study drug was found to be compatible with formulation
excipients. Gelation temperature and pH of all formulation found to be in the range of
40- 250oC and 5.5-5.9 respectively. Viscosity of all prepared formulations was found
in the range of 600-1500 cps. All the formulations except F3, F6 and F9 show
satisfactory syringeability. The developed formulations showed satisfactory results for
in-vitro gelling capacity, rheology and other physical properties. Based on maximum
desirability and cost effectiveness formulation containing 0.32%w/v of gellan gum
and 14.2%w/v of poloxamer 407 was consider as an optimized batch. 30
Lacramioara P, et al (2013), reported a drug delivery system based on a series of
formulations with chitosan gels, designed
for local, intra-pocket treatment of
periodontal disease, containing two drugs (an antibiotic and a chemotherapeuticantimicrobial agent: tetracycline hydrochloride (T) and metronidazole benzoate (M),
respectively. The formulations varied from the chitosan concentration (3-4%), and the
drug loading (1,2 and 3%). All formulations exhibited pseudoplastic and thixotropic
behaviour. An optimum concentration of chitosan in gel (3%) is used for modulation
of drug loading, as a success factor in local therapy of periodontitis. 31
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Mahendra D, et al (2012), described the formulation of ciprofloxacin loaded cubic
phase gels, a biodegradable, bioadhesive, biocompatible delivery system and their
characterisation for drug content, drug loading efficiency, gelation temperature, gel
melting temperature, pH, bioadhesive force, viscosity, gel strength, swelling and drug
release profile. Gels were prepared with glyceryl monooleate (GMO), glyceryl
monostearate (GMS), methyl cellulose, Tween 80 and Span 80. The formulations with
high concentrations of methyl cellulose and GMS, demonstrated higher swelling
characteristics. The addition of methylcellulose or GMS to the GMO-water system
transformed the rheologic property to pseudoplastic flow which also affected the drug
release attributes of the formulations. 32
Eskandar M, et al (2012), reported formulation and characterization of oral
mucoadhesive chlorhexidine tablets using Cordia myxa mucilage. In this study the use
of mucilage of Cordia myxa as a mucoadhesive material in production of
chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC
was studied. The persuade of mucilage concentration on the physicochemical
responses (hardness, friability, disintegration time, dissolution, swelling, and
mucoadhesiveness strength) was studied and swelling of mucilage and HPMC were
compared. The evaluated responses included the force needed to separate tablets from
mucosa, and the amount of water absorbed by tablets. Also, compared to 30% HPMC,
muco-adhesiveness strength of buccal tablets containing 20% mucilage was
significantly higher. It is stated that the presence of Cordia myxa powdered mucilage
may significantly affect the tablet characteristics, and increasing in mucoadhesiveness may be achieved by using 20% w/w mucilage. 33
Mohammed G, et al (2012), designed minocycline hydrochloride microspheres as
local delivery in treatment of periodontitis. In this microspheres of minocycline
hydrochloride were prepared. Compatibility studies by FTIR indicated that there was
no chemical interaction between drug and polymer.The microspheres were prepared
by emulsion cross linking method using chitosan as a polymer and were evaluated for
drug content, size analysis and stability studies. Further the optimized microspheres
and pure drug were formulated into in situ gels by using gellan gum. The in vitro
diffusion study was done for these developed in situ gel formulations. From the
stability studies no appreciable difference was observed in the extent of degradation
of product during 60 days when stored at 40°C/ 75% RH. 34
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Raghavendra N, et al (2012), reported formulation, in vitro characterization and
clinical evaluation of ofloxacin medicated dental gels for periodontal infections. The
ofloxacin dental gels were prepared with different hydrophilic polymers methyl
cellulose, hydroxy propyl methyl cellulose, hydroxy propyl cellulose and hydroxy
ethyl cellulose in different conc. of propylene glycol. These formulations were tested
for physico-chemical studies. Gels were found to exihibit non-newtonian and
pseudoplastic behaviour. It was stated that ofloxacin gels along with scaling and root
planning results in significant benefits in the treatment of periodontitis. 35
Baksh A, et al (2012), reported formulation and in vitro evaluation of NSAID’s gel.
In this study transdermal permeation of Diclofenac Sodium was achieved. Permeation
studies were carried out in vitro using Cellophane Membrane. Topical gel
formulations of diclofenac sodium were prepared by using polymer as a gel-forming
material that is biocompatible and biodegradable. In vitro permeability study showed
that permeation studies of Carbopol 934 and marketed gel were comparable and for
Carbopol 934 was more. The gel preparation is excellent in the percutaneous
absorption of diclofenac. 36
Katiyar A, et al (2012), described formulation and evaluation of dental films for the
treatment of dental films. Films containing lomefloxacin hydrochloride were
developed in a non bio-degradable carrier for targeted delivery of drug. Ethyl
cellulose was used as polymer. The films were then evaluated for in vitro, in vivo
release studies. 37
Shilpi P, et al (2011), formulated mucoadhesive submicron emulsion (MuSME) for
periodontal delivery. Mucoadhesive submicron emulsion of metronidazole has been
developed and investigated for its in vitro drug release, ex vivo permeation effects and
also for antimicrobial susceptibility against Porphyromonas gingivalis. The pseudoternary phase diagram was done using isopropyl myristate (IPM), Tween 80, lecithin
and water. Chitosan is was used as mucoadhesive agent and the permeation rates i.e.
steady state flux of metronidazole from MuSME was found to be 1.2 times greater
than that from a conventional formulation and 46.6 times more than that from a 1%
alcoholic solution of the drug. 38
Priyanka M, et al (2011), developed controlled release periodontal formulation of
Secnidazole-Serratiopeptidase used in the treatment of periodontitis. The pH sensitive
and mucoadhesive formulations consist of non-toxic polymer, Sodium alginate (1%),
HPMC E50Lv (1-8%w/w). To modulate the gel strength and the bioadhesive force of
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gel HPMC E50Lv was used as viscosity enhancer. Viscosity studies showed pseudo
plastic behavior of gel. Increase in polymer concentration showed increase in the
viscosity thereby affecting the drug release. Dissolution studies demonstrate diffusion
release of drug and enzyme from the gel thus alginate/HPMC gels can be used as an
in-situ gelling vehicle to enhance periodontal drug delivery. The formulation A6 was
found to be optimum to the above parameters. 39
Adamo F, et al (2011), discussed the in vitro/in vivo buccal release of (CHX) from
mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive
properties: CHX digluconate was present at a constant 1% w/v concentration the
mucoadhesive
gel
forming
materials
were
carboxymethyl-
(CMC),
hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC) cellulose, alone (3% w/w)
or in binary mixtures (5% w/w); gels were tested for their mucoadhesion using the
mucin method at 1, 2 and 3% w/w concentrations. CHX release from different
formulations was assessed also combining release/permeation process in which
porcine mucosa was placed in a Franz cell was done. The combination of HPMC or
HPC with CMC showed slower drug release. 40
Sanjay S, et al (2011), developed topical bioadhesive gel of aceclofenac by using
combination of Poloxamer 407 and HPMC employing the response surface approach.
The effect of formulation variables on the product characteristics were predicted and
precisely interpreted by using a 3-level factorial experimental design and
mathematical equations. On the basis of product characteristics such as bioadhesive
strength, consistency index and in-vitro release, it can be concluded that the best batch
of topical bioadhesive gel of Aceclofenac would be with 20% PL-407 and 3% HPMC.
41
Shivakumar Y, et al (2010), formulated metrodinadazole gel for local treatment. Six
batches of metronidazole gels were prepared using natural biodegradable polymers
Chitosan, guar gum and Locust bean gum in variable concentrations and
were
evaluated. The results revealed that the surface pH was within the range of neutral pH.
The bioadhesion strength was maximum for F3 formulation (3% Chitosan); viscosity
values were ranging from 1453.33 ± 5.77 to 1995.00 ± 0.01 dyne/cm2. Best
formulation in terms of drug release along with bioadhesion was formulation F3 with
78.23% drug release for 7 days Zone of inhibition was also acceptable for all the
formulations. 42
10
Kotchamon Y, et al (2010), showed the use of modified starch as gel base of
chlorhexidine gluconate for periodontitis treatment. Modified starch FA8704 was
employed as the gel base for local delivering of chlorhexidine gluconate.
Physicochemical properties were tested. A gel base comprising 24% w/w of FA8704
was selected to incorporate chlorhexidine gluconate (CHX). Viscosity of gel
depended on the modified starch FA8704. CHX gel exhibited a higher antimicrobial
activity against S. aureus than against other tested microbes. The gel base displayed
the antimicrobial activity against S. aureus and E. coli. The in vitro release study
indicated that FA8704 gel could extend a release of CHX. 43
Jafar A, et al (2010), formulated mucoadhesive chlorhexidine tablets and evaluated
their drug release characteristics. Chlorhexidine buccal adhesive tablets were prepared
by direct compression using a blend of hydroxypropyl methylcellulose (HPMC) and
chitosan as the bioadhesive polymers. Dissolution were performed. Results showed
that as the proportion of HPMC in the blend increased, drug release rate decreased,
with the lowest release rate observed when HPMC alone was used as the bioadhesive
polymer. Bioadhesion force increased with increasing proportion of HPMC, with the
highest adhesion force shown when HPMC was the only polymer used, and lowest
when chitosan was used alone. 44
Vikesh S, et al (2010), prepared ornidazole gel using natural polymers. Here, six
batches of Ornidazole gels were prepared using natural biodegradable polymers
Chitosan, Xanthum gum and Locust bean gum in changeable concentrations. The
formulated gels were characterized for surface pH, viscosity, bioadhesion strength, in
vitro drug release studies and antimicrobial susceptibility test. The results revealed
that the surface pH was within the range of neutral pH. The bioadhesion strength was
maximum for F3 formulation (3% chitosan); viscosity values were ranging from 1400
to 1975 dyne/cm2. In terms of cumulative percent drug release along with bioadhesion
was formulation F3 with 79.23% drug release for 7 days was best. Zone of inhibition
was also acceptable for all the formulations. 45
Ramdan E, et al (2010), reported metronidazole (Mz) incorporation into different
bioadhesive matrices together with gels and films using carbopol 934p (4%), chitosan
(3%) and hydroxypropyl methyl cellulose (HPMC) (3%). Penetration enhancers
including menthol (1%) or oleic acid (OA) (5%, 10%) were incorporated in such
formulations. Permeability of Mz across ear rabbit skin and enhancement ratios (ER)
were studied. The obtained results showed that the gel formulations containing
11
carbopol 934p exhibited maximum bioadhesive force with detachment stress equals to
66.98x102 dyne/cm2 followed by those containing chitosan (42.45x102 dyne/cm2)
and HPMC (26.41x102 dyne/cm2). Bioadhesive chitosan gel containing menthol had
accelerated the periodontal wound healing more than chitosan based film containing
oleic acid. 46
Swati R, et al (2010), developed in situ gel formulation of ornidazole for the
treatment of periodontal disease. A biocompatible and biodegradable syringeable insitu gel formulation of Ornidazole having controlled release was developed using
Poloxamer 407(Pluronic F-127). The drug and polymer were characterized by
preformulation studies. Cold method is chosen as lump formation takes place in case
of hot process. Evaluation for various parameters like gelation temperature, drug
content, bioadhesive strength, syringeability, viscosity, in vitro drug release and
antibiotic activities. In-vitro drug release showed that SO1 formulation released the
drug completely within 8 hour. The antibiotic assay of Ornidazole gel was performed
against E.coli, S.aureus and isolated coagulase negative Staphylococcus spp. The
results of study indicate that, Pluronic F-127 is promising polymer to develop in-situ
gel formulation for periodontal disease. 47
Shivanand P, et al (2009), reported study of medicated chewing gum containing
Chlorohexidine gluconate. Concentration of 50% synthetic gum base give promising
results with the water soluble drug Chlorhexidine gluconate for steady drug release
coupled with adequate release properties from medicated chewing gum(MCG).
Synthetic gum formulations are similar marketed medicated chewing gum in
appearance. Since synthetic gum base has 50 % gum base used to formulate MCG
compared to market medicated chewing gum this should provide a more pleasant
mouth feel and it was expected that this would result in a steady and controlled
release of drug. 48
Yael S, et al (2009), developed metronidazole loaded bioabsorbable films as local
antibacterial treatment of infected periodontal pockets. In this study we developed and
studied metronidazole-loaded 50/50 poly (DL-lactide-co-glycolide) (PDLGA), 75/25
PDLGA, and poly (DL-lactic acid) (PDLLA) films. The structured films were
prepared using the solution- casting technique. The PDLLA and 75/25 PDLGA films
generally exhibited a low- ormedium-burst release followed by a moderate release at
an approximately constant rate, whereas the 50/ 50 PDLGA films exhibited a biphasic
release profile. The drug released from films loaded with 10% weight/weight
12
metronidazole resulted in a significant decrease in bacterial viability within several
days. 49
Jeon Y, et al (2007), prepared and evaluated ketorolac trometnamine gel containing
genipin for periodontal diseases. Ketorolac tromethamine gel (KT gel) and ketorolac
tromethamine gel containing genipin (KTG gel) were prepared and their therapeutic
effects on periodontitis were evaluated. The skin permeation rate of for KT gel and
KTG gel was 5.75±0.53 and 5.82 ± 0.74 μg/cm2/ h, respectively. The tensile strength
of the KTG gel was larger than the KT gel. The KTG gel appears to be effective
against gingivitis in the periodontal pocket through its augmented anti-inflammatory
activity and the crosslinking of genipin with the biological tissue. 50
Isaac C, et al (2004), developed a novel polymeric device for the treatment of
periodontal disease. Microparticles of poly(dl-lactic-co-glycolic acid) (PLGA)
containing chlorhexidine (Chx) free base, chlorhexidine digluconate (Chx-Dg) and
their association or inclusion complex with methylated-b-cyclodextrin (MBCD) and
hydroxypropyl-b-cyclodextrin (HPBCD) were prepared by single emulsion, solvent
evaporation technique. The PLGA/CD delivery system may prove useful for the
localized delivery of chlorhexidine salts and other anti-microbial agents in the
treatment of periodontal disease where prolonged-controlled delivery is needed. 51
Perugini P, et al (2003), designed a film dosage form for sustained delivery of
ipriflavone into the periodontal pocket. Complex systems made of ipriflavone loaded
poly(d,l-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were
obtained by emulsification/casting/evaporation technique. Multilayer films, made of
three layers of polymers (chitosan/PLGA/chitosan), were also made. Morphology and
physico-chemical properties of the different systems were evaluated. The influence of
pH, ionic strength and enzymatic activity on film degradation, was also studied.
Significant differences in swelling, degradation and drug release were highlighted,
depending on film structure and composition. In vitro experiments demonstrated that
the composite micromatricial films represent a suitable dosage form to prolong
ipriflavone release for 20 days. 52
Philippe G, et al (2002), studied chitin-based gel as injectable material in periodontal
surgery. The optimal conditions correspond to a time of 2 min 15 s. They are achieved
for
acetylation
parameters
corresponding
to:
a
molar
ratio
acetic
anhydride/glucosamine residue, R = 1.5; a temperature of the master solution of
121oC, a mixture of hydroalcoholic solution/acetylating reactive stirred for 45s at
13
room temperature and a chitin concentration of 3.6%. This concentration allows us to
limit the syneresis, to improve the mechanical properties of the gel and to obtain a
viscosity suitable for the injection. Mixing of the gel by means of chitosan powder
insoluble under these conditions allows us to consider an improvement of the
biological activity of the gel. 53
Senel S, et al (2000), reported chitosan films/ hydrogels of chlorohexidine gluconate
for oral mucosal delivery. Chitosan, a partially deacetylated chitin, which is a safe
biopolymer, prolongs the adhesion time of oral gels and drug release from them.
Chitosan also inhibits the adhesion of Candida albicans to human buccal cells and has
antifungal activity. Chlorhexidine gluconate (Chx) also reduces C. albicans adhesion
to oral mucosal cells. Gels or film forms of chitosan were prepared containing 0.1 or
0.2% Chx and their in vitro release properties were studied. Release of Chx from gels
was maintained for 3 h. The maximum antifungal activity was obtained with 2%
chitosan gel containing 0.1% Chx. 54
Natalie J, et al (1996), reported chlorhexidine release from poly(-caprolactone)
films prepared by solvent evaporation. The effect of selected formulation variables on
the release of chlorhexidine from poly(e-caprolactone) films was evaluated in vitro
using a complete factorial experimental design. Transecting sections of film, prepared
with chlorhexidine diacetate < 63 gm (drug loading 20% w/w), and analysing the
chlorhexidine content at altering distances from the film surfaces showed a gradient in
chlorhexidine concentration through the film. 55
Ian G, et al (1995), studied the parameter bioadhesion for periodontal and buccal
drug delivery. Bioadhesion could significantly improve oral therapeutics for
periodontal diseases and mucosal lesions. Study of factors important to prolonged
adhesion (adhesion time) in organ culture under standardized conditions. A wide
variety of bioadhesives were tested in the model and the effect of mucin was also
examined. While many gels adhered for 1-5 h, others (chitosan and Eudispert) showed
no retention loss over 4 days. Histologically, chitosan also showed excellent tissue
wetting properties. For most materials, however, mucin considerably reduced
adhesion times (P < 0.05). In conclusion, the absence of mucin, the control of gel
hydration and swelling, and wetting characteristics were identified as key factors for
prolonged adhesion. 56
14
Roskos K, et al (1995), developed a drug delivery system for the treatment of
periodontal disease using bioerodible poly (ortho esters). Poly (ortho esters) prepared
by the condensation of 1,2,6 hexanetriol and an alkyl orthoacetate are viscous,
semisolid materials at room temperature that can be injected using a blunt needle.
When tetracycline was incorporated into these materials, complete release occurred
within about 24 hours, but when small amounts of Mg(OH)2 were incorporated into
the polymer release could be extended to many weeks, and a loading of 0.5 wt%
resulted in sustained release of about 10 days. Adhesive and cohesive forces were
tested. The combination of injectability, dentoadhesiveness and ability to control
accurately the release of incorporated antibiotics makes these materials promising
candidates for bioerodible delivery systems useful in the treatment of periodontitis. 57
DRUG: Chlorhexidine is a broad-spectrum biocide effective against Gram-positive
bacteria, Gram-negative bacteria and fungi. Chlorhexidine inactivates microorganisms
with a broader spectrum than other antimicrobials (e.g. antibiotics) and has a quicker
kill rate than other antimicrobials (e.g. povidone-iodine). It has both bacteriostatic
(inhibits bacterial growth) and bactericidal (kills bacteria) mechanisms of action,
depending on its concentration. Chlorhexidine kills by disrupting the cell membrane.
Upon application in vitro, chlorhexidine can kill nearly 100% of Gram-positive and
Gram-negative bacteria within 30 seconds. In topical applications, chlorhexidine is
shown to have the unique ability to bind to the proteins present in human tissues such
as skin and mucous membranes with limited systemic or bodily absorption. Protein
bound chlorhexidine releases slowly leading to prolonged activity. This phenomenon
is known as substantivity and allows for a longer duration of antimicrobial action
against a broad spectrum of bacteria and fungi.
In fact, chlorhexidine's antimicrobial activity has been documented to last at least 48
hours on the skin. In oral applications, chlorhexidine binds to the mouth tissue, oral
mucosa and teeth. This helps to reduce the bacterial count and prevents dental plaque.
It has become the gold standard in dentistry due to its ability to adhere to soft and
hard tissue and maintain a potent sustained release. Chlorhexidine, when applied to or
impregnated in medical devices kills organisms and protects against microbial
colonization and subsequently biofilm development.12
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