DENTAL IMPLANT AS NOVEL DRUG DELIVERY SYSTEM

PRESENTED BY GOURAV SINGH

M.PHARM 1ST YEAR

INTRODUCTION

Dental implant for the treatment of periodontal diseases was developed for

site specific delivery of drug.

Systemic administration has been useful in treatment of periodontal diseases, but repeated and long term use of systemic drugs will lead resistant strains and side effects .

These problem can be overcome if drug to be used is applied locally. Concentration of drug in tissues can be enhanced by incorporating the drug into controlled release delivery system and implant them directly into periodontal pocket.

A local drug delivery system delivering the therapeutic agent at sufficient concentration inside the pocket and minimizing the side effects associated with systemic drug administration.

Tooth structu

re

Periodontal disease

Periodontal disease is characterized by inflammation of periodontal tissues, leading to degeneration of the periodontium it will lead to pocket formation or recession, tooth mobility and finally tooth loss.

periodontal pockets are dental terms indicating the presence of an abnormal depth of the gingival sulcus near the point at which the gingival tissue contacts the tooth

Principles and Goal

Principles

Periodontal pocket provides a natural reservoir bathed by GCF (gingival crevicular fluid), which is easily accessible for the insertion of delivery devices. The gingival fluid provides a leaching medium for the release of a drug from the solid dosage form and for its distribution throughout the pocket. Thus this makes the periodontal pocket a natural site for treatment with local release delivery system.

Goal

The primary goal in using an intra pocket device for the delivery of an antibacterial agent is to achieve and maintain the therapeutic levels of the drug for the required period of time. This inhibits or kills the pathogens, without any harm to the tissue.

Advantages and Disadvantages of Dental Implant

Advantages Attain 100 fold higher concentrations of an antimicrobial

agent in subgingival sites. Reduce the risk of developing drug resistant. Employ antimicrobial agents which is not suitable for

systemic administration Maintain effective concentrations of antimicrobial agent for

longer periods of time.

Disadvantages Time consuming Relatively Costly

Drug delivery systems for treating periodental diseases

Fibers Film Injectable systems Gels Strips and compacts Vesicular systems Microparticle SystemNanoparticulate System

FIBERS

Fibers, or thread-like devices, are reservoir-type systems, placed circumferentially into the pockets with an applicator and secured with cyanoacrylate adhesive for the sustained release of then trapped drug into the periodontal pocket.

Films

A far more widely used form of intra-pocket delivery device has been in the shape of film, prepared either by solvent casting or direct milling. Bigger films either could be applied within the cavity onto the cheek mucosa or gingival surface or could be cut or punched into appropriate sizes so as to be inserted into the site of action. Films are matrix delivery systems in which drugs are distributed throughout the polymer and release occurs by drug diffusion and/or matrix dissolution or erosion.

INJECTABLE SYSTEM

Injectable systems are particularly attractive for the delivery of antibiotic agents into the periodontal pocket. The application can be easily and rapidly carried out, without pain, by using a syringe.

Gels

Mucoadhesive, MTZ containing gel systems based on hydroxyethyl cellulose, corbopol 974, and polycarbophil have been made. Gel is applied sublingually with the help of blunt cannula and syringe. The gel is only marginally affective in decreasing the anaerobic bacterial count.

Injectable Gels

Together with the solid devices, semisolid formulations also receive reasonable attention for the localised delivery of antibiotics. Semisolid or gel formulations can indeed have some advantages. In spite of the relatively faster release of the incorporated drug, gels can be more easily prepared and administered.

Various oleogels and hydrogels for the delivery of tetracycline (2.5%), metronidazole (25%), metronidazole benzoate (40%), as well as a combination of tetracycline (2.5%) and metronidazole benzoate (40%), have been tested and satisfactory results have been achieved .

Strips and Compacts

Acrylic strips have been fabricated using a mixture of polymers, monomers and different concentrations of ant microbial agents. Strips were fabricated either by solvent casting or pressure melt method. Strips containing tetracycline, MTZ or chlorhexidine .

Vesicular Systems

Vesicular liposomal systems are designed to mimic the bio-membranes in terms of structure and bio-behaviour, and hence are investigated intensively for targeting periodontal biofilms.

The targeting of liposomes was thought to be because of the interaction of the polyhydroxy groups of liposomes with surface polymers of the bacterial glycol-calyx.

Succinylated Concanavalin-A (lectin)-bearing liposomes (proteoliposomes) have been found to be effective for the delivery of triclosan to periodontal biofilms.

Microparticle System

Microparticles based system of biodegradable poly alpha hydroxy acids such as poly lactide (PLA) or poly (lactide – co-glycolide) PLGA containing tetracycline has been designed for periodontal disease therapy.

Microparticles of poly (dl-lactic-coglycolic acid) (PLGA) containing chlorhexidine free base, chlorhexidine di gluconate and their association or inclusion complex with methylated-beta-cyclodextrin were prepared with single emulsion, solvent evaporation technique.

Nanoparticulate System

Modern drug delivery systems are designed for targeted controlled slow drug release. Up to now polymer or microparticle-based hydrogels have been applied in dentistry, which can affect the rate of release because of their structure. These systems reduce the frequency of administration and further provide a uniform distribution of the active agent over an extended period of time.

Biocompatible nanoparticles composed of 2-hydroxyethyl methacrylate and polyethyleneglycol dimethacrylate could be used as a drug delivery system for dental applications.

Dental Implant drug delivery devices

Drug delivery devices can be divided into 2 classes

Sustained release formulations designed to provide drug delivery for less than 24 hours, eg:- Metronidazole Gel.

Controlled delivery systems having a drug release of duration of more than 1 day, eg:- Chlorhexidine Gluconate Chip.

Preparation of Dental Implant By Solvent Casting Technique

EVALUATION

Uniformity of thickness Five films were taken from each batch and their

individual thickness was measured using micrometer screw gauge.

Uniformity of weight Five films were taken from each batch and their

individual weights were determined by using electronic balance.

Uniformity of drug content Five films were taken from each batch and individually

dissolved in 5 ml of pH 6.8 phosphate buffer in a beaker and filtered it. 0.1 ml of the filtered solution was diluted to 10 ml with pH 6.8 phosphate buffer in a 10 ml volumetric flask. Three reading were taken using UV spectrophotometer.

Tensile strength of the films Tensile strength of the films was determined by

Universal strength testing machine. It consists of two load cell grips, the lower one is fixed and upper one is movable. The test film of specific size (4 × 1 cm2) was fixed between these cell grips and force was gradually applied till the film breaks. The tensile strength of the film was taken directly from the dial reading in kilograms.

Folding endurance The folding endurance of the films was determined

by repeatedly folding the film at the same place up to 300 times till it broke or folded, which is considered satisfactory to reveal good film properties. This test was carried out on all the films.

Viscosity Aqueous solutions containing both polymers and

plasticizers were prepared in the same concentration as that of films. Viscosity was measured at 20 rpm at room temperature using Brookfield viscometer (LVDV‐E model) attached to the helipath spindle number 18. The recorded values were mean of five determinations.

In vitro antibacterial activity: The films (size of 2x2 mm2) containing 26.6μg of

drug were taken for the study.Prepare and sterilize nutrient agar medium by autoclaving under aseptic condition and transfer the medium to sterile Petri plates. After solidification of nutrient agar medium, made a lawn with 0.1 ml microorganism i.e. S. aureus and E. coli in separate Petri plates, over that the films were placed and incubate for 48 hrs at 370 C.

DRUG POLYMER METHOD OF PREPARATION

Ornidazole Ethyl Cellulose Solvent casting technique

Cefuroxime axetil Ethyl Cellulose Solvent casting technique

Tetracycline Ethylene/ Vinyl Acetate

Solvent casting technique

Chlorhexidine gluconate

Glutaraldehyde Solvent casting technique

Doxycycline Ethylene Vinyl Acetate Solvent casting technique

Metronidazole Ethyl Cellulose Solvent casting technique

System Polymer matrix Drug Incorporated

Fibers

Cellulose acetate Ethylene vinyl acetatePoly(e-caprolactone) (PCL)

Tetracycline HCl Chlorhexidine Tetracycline HCl Tetracycline HCl

Strip

Polyethylmetha acrylate (acrylic) Hydroxypropyl cellulose HPC + methacrylic acid Ofloxacin Polyhydroxybutyric acid Polylactide-co-glycolic acid (PLGA) Ethyl cellulose

Tetracycline HCl ,Metronidazole Chlorhexidine, tetracycline Doxycycline Tetracycline HCl Tetracycline HClChlorhexidine Chlorhexidine

Films

Ethyl celluloseCross-linked atelocollagen Gelatin (BycoW protein) Cross-linked gelatin + glycerine Chitosan Chitosan + PLGA

Metronidazole, Minocycline Tetracycline HCl TetracyclineChlorhexidine diacetateChlorhexidine digluconateTaurineIproflavone

Gels

ChitosanHEC + polyvinylpyrrolidone HEC + polycarbophil Poloxamer 407 + Carbopol 934P Glycerol monooleate + sesame oil PLGA

MetronidazoleTetracycline MetronidazolePropolisMetronidazoleTetracycline

Microparticle Pluronic F 127 PLGA PLGA + PCL

TetracyclineTetracyclineHistatin peptides Doxycycline

Nanoparticles PLGA Chitosan oligonucleotide Cellulose acetate phthalate

Harungana madagascariensis leaf extract AntisenseTriclosan

THANK YOU