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In Vitro Sustained Release of Calcium Ions And

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    Nidambur Vasudev Balla

    Gopal Venktesh Shavi,Ranjith Kumar,

    Mala Kundabala.

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    y Calcium hydroxide used -1920s.

    y Introduced by Hermann.

    clinical applications

    y an antimicrobial agent,

    y controlling exudates from root canals,

    y arresting inammatory root resorption,

    y inducing calcic response,

    y root canal sealer.

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    y MOA

    By dissociating into calcium and hydroxyl ions

    increasing pH locally (Tronstad et al) .

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    Benecial effect is due to

    y Break up of fatty acids in gram-negative bacteria,

    y inactivation of endotoxins,

    y damage to the bacterial DNA

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    y Efcacy [Ca(OH)2]

    availability of hydroxyl ions in solution

    dependent on vehicle that is used.

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    y Medicament vehicle very imp. role in overalldisinfection

    y determines velocity of ionic dissociation,

    y enable paste to be solubilized / resorbed at

    varying rates.

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    y Lower the viscosityhigher ionic dissociation .

    y High mol. wt. of common vehicles

    minimizes dispersion into the tissue

    maintains paste in desired area for longer

    duration .

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    Three main types of vehicles used:

    (1)water soluble substances

    water, saline, local anesthesia, ringers solution

    (2) viscousvehicles

    glycerin, polyethylene glycol, and propyleneglycol (PG)

    (3) oil-based vehicles olive oil, silicone oil, camphor, eugenol,

    metacresylacetate

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    y In 1982,

    yAnthony et al studied effect of vehicles on pH ofcalcium hydroxide.

    y Concluded that calcium ions diffuse throughapical foramen and change the PH.

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    y Chitosan natural polysaccharide widely usedpharmaceutic excipient.

    y synthesis -partial deacetylation of chitin,

    y derivative of exoskeleton of arthropods.

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    y copolymers of glucosamine and N-acetyl glucosamine .

    biological actions:

    y hypocholesterolemic

    y antimicrobial

    y wound healing

    y mucoadhesivey sustained release

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    y products available as powder, paste.

    y combined with collagen sponge as a barriermembrane in periodontal therapy

    y an oral mucosal delivery agent for chlorhexidineagainst Candida albicans .

    y Ballal et al

    y chitosan enhanced sustained release of chlorhexidinegluconate against Enterococcus faecalis.

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    y Guar gum gum from ground endosperms -cyamopsis tetragonlolbus.

    y highmol.wt. hydrocolloidal polysaccharide ofgalactose and mannan units.

    y used in cosmetics, food products and pharmaceuticformulations as a binder and thickening agent

    y Has a sustained release property (George and Abraham)

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    y Chitosan (85% deacetylated) Sigma-AldrichChemicals, Taufkirchen, Germany.

    y PG, polyethylene glycol 6000 (PE 6000), and guar gum( Universal Lab. Mumbai, India).

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    y Hydrophilic polymers

    y PG, PEG 6000, chitosan, and guar gum were used .

    y Different concentrations of hydrophilic polymers for desired release of calcium ions

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    y Ethical clearance Ethical Committee (IEC 008/2009)of Manipal University, Manipal, Karnataka, India.

    y 40 human maxillary anterior teeth ---extracted for

    periodontal reasons .

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    y Soft-tissue remnants on tooth surface -removed usinga soft brush.

    y Teeth examined for fractures, cracks, or any otherdefects using magnifying loupes.

    y Teeth stored in solution of 0.05% sodium azide innormal saline at 4 degree C

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    y Solution changed daily until sufcient number ofsamples were collected.

    y The crowns of all the teeth were removed at the CEJ

    using a diamond disc 15 mm.

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    y The root canal was enlarged initially up to size 20using K-les , and the pulp tissue was removedusing barbed broach.

    y working length of the root canal was determined .

    y each tooth was instrumented upto size 45 apically.

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    y Coronally the canal was enlarged using G. G .drillsno. 2 to 5.

    y After each instrument, the canal was passively

    irrigated with 2 mL of 2.5% NaOCl .y The nal irrigation was performed with 2 mL of

    17% EDTA solution

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    y Finally, the root canal was ushed with 5 mL ofdistilled water .

    y The teeth were then divided into four group :

    group 1PGgroup 2 PEG 6000

    group 3 chitosan

    group 4guar gum

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    y A vial method was adopted .

    y Accurately measured quantities of differentformulations were performed to the root canal using

    K-les up to 1 mm short of the working length.y The formulations were further condensed with an

    endodontic nger plugger.

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    y While lling the root canals, each root was held in amoist gauze to prevent the smearing of theformulations onto the root surface .

    y

    The orice of the root canal of all the teeth was sealedwith GIC

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    y The teeth were then suspended in the glass vials -10mL of distilled water.

    y the pH and the calcium ion concentrations weremeasured.

    y

    Solutions of 3.0 mLwere then withdrawn periodicallyat predetermined time intervals up to 24 hours and at7, 15, and 30 days.

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    y The vials were tightly closed with the help ofmolding wax.

    y The solutions were analyzed using an ultraviolet

    spectrophotometer at 220 nm .

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    y The change in pH of all the different formulationswas determined by pH meter

    y Each sample was tested three times, and the mean

    value for each experimental group was calculated

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    y PG showed cumulative drug release of 96.64%

    0.56% at the end of 15 daysy PEG 6000, chitosan, and guar gum showed cumulative

    drug release of 98.22% 0.25%, 86.88% 0.68%, and96.03% 0.42%, respectively, at the end of 30 days.

    y Among all the formulations tested, chitosan showed acumulative drug release of 86.88% 0.68% for aperiod of 30 days

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    y The pH of different groups on rst day was found to be7.0.

    y After 30 days, pH was found to be 10.3, 10.7, 10.2, and11.2.

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    y The imp. of the alkalinizing effects of calciumhydroxide and its capacity to produce OH ions in theperiapical environment has been reported

    y Nerwich et al pH changes in root dentin over a 4-week period and considered as a reasonable timeinterval to expect effective therapeutic benets .

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    y Placing a formulation of calcium hydroxide with anappropriate vehicle, which can sustain high alkalinepH in the periapical area.

    y In the present study, all the formulations showed ahigh alkaline pH (>10) at the end of 1 month.

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    y The dissociation of calcium hydroxide in differentvehicles has been shown to be the most efcient way torelease hydroxyl ions .

    y

    Vehicles can also prolong the duration of the drugeffect signicantly and improve the bioavailability ofthe drug

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    y an ultraviolet spectrophotometer was adoptedbecause of its rapid analysis and the cost of the

    analysis is less expensive

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    y All the vehicles used in this study to prepare thecalcium hydroxide gel were biodegradable.

    They offer many advantages

    y targeting the drug to the specic sites,y controlled release of the drug,

    y protection of either the host or the encapsulated drug.

    y the drug release rate can be controlled by the selection

    of the mol. wt .of the polymer and its compositions

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    y chitosan is the second most abundant organic materialnext to cellulose .

    exhibits favorable biological properties such as

    y nontoxicity,y biocompatibility,

    y biodegradability has attracted much interest inpharmaceutic research as a polymeric drug carrier

    y as a novel drug absorption enhancer across nasal andintestinal epithelia

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    y The release pattern with chitosan was biphasic inmanner.

    y The burst release of calcium ions with chitosan in the

    initial stages could bey to the drug present at the surface of the polymer.

    y because of the presence of free amino groups

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    y Chitosan when used as a vehicle exhibited a controlledrelease of calcium ions .

    y All four vehicles maintained a high alkaline pH at the

    end of 1 month.y the effect of degradable products on the penetration

    of intracanal medicaments, sealers, or adhesive resinsinto the dentinal tubules has to be evaluated.

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