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DENTAL IMPLANT AS NOVELDENTAL IMPLANT AS NOVEL
DRUG DELIVERY SYSTEMDRUG DELIVERY SYSTEM
PRESENTED BY
SUDHANSHU GANGWAR
M.PHARM 1st
year
INTRODUCTIONINTRODUCTION
 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 Structure
PERIODONTAL DISEASEPERIODONTAL 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.
PERIODONTITIS DISEASEPERIODONTITIS DISEASE
 Periodontitis is inflammation of the gingival and the adjacent attachment
apparatus and is characterized by loss of connective tissue attachment and
alveolar bone.
 Periodontitis is a chronic bacterial infection that affects the gums and bones
supporting teeth
 Antibacterial agents have been used effectively in the management of
periodontal infection.
 The use of sustained release formulations to deliver antibacterials to the site of
infection (periodontal pocket) has recently gained interest.
GINGIVITIS DISEASE
 Gingivitis is inflammation of the gingiva.
 Gingivitis is often caused by inadequate oral hygiene. Periodontal disease can
affect one tooth or many teeth.
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
PERIODONTAL
POCKET
PRINCIPLES AND GOALPRINCIPLES 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 DISADVANTAGESADVANTAGES AND DISADVANTAGES
OF DENTAL IMPLANTOF 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 FORDRUG DELIVERY SYSTEMS FOR
TREATING PERIODENTALTREATING PERIODENTAL
DISEASESDISEASES
Fibers
Film
 Injectable systems
 Gels
 Strips and compacts
 Vesicular systems
Microparticle System
Nanoparticulate System
FIBERSFIBERS
 Fibers, or thread-like devices, are reservoir-type systems, placed
into the pockets with an applicator and secured with cyanoacrylate
adhesive for the sustained release of then trapped drug into the
periodontal pocket.
 The release of the tetracycline from the cellulose acetate fibres as
occurred by diffusion mechanism is rapid with approximately 95%
of the drug released in the first two hours , single application of
these fibres does not provide an effective drug concentration for
long periods.
 Compared with the less effective tetracycline delivery from hollow
fibres, fibres containing 20% (v/v) chlorhexidine, when placed into
periodontal pockets, exhibited a prompt and marked reduction in
signs and symptoms of periodontal disease.
FILMSFILMS
• 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 SYSTEMINJECTABLE 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.
GELSGELS
 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.
 The results indicated that an increase in carbopol
concentration significantly increased gel
compressibility, hardness and adhesiveness factors that
affect ease of gel removal from container, ease of gel
application onto mucosal membrane, and gel
bioadhesion.
INJECTABLE GELSINJECTABLE 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 COMPACTSSTRIPS 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 .
Chitosan, a novel biodegradable natural
polymer, in a gel form (1%, w/w) with or
without 15% metronidazole, had
demonstrated effectiveness in the
VESICULAR SYSTEMSVESICULAR 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 SYSTEMMICROPARTICLE 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 SYSTEMNANOPARTICULATE 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 DELIVERYDENTAL IMPLANT DRUG DELIVERY
DEVICESDEVICES
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 SolventPreparation of Dental Implant By Solvent
Casting TechniqueCasting Technique
EVALUATIONEVALUATION
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
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
 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 26.6 g of drugμ
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 acetate
Poly(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 HCl
Chlorhexidine
Chlorhexidine
FILMS
Ethyl cellulose
Cross-linked atelocollagen
Gelatin (BycoW protein)
Cross-linked gelatin + glycerine
Chitosan
Chitosan + PLGA
Metronidazole, Minocycline
Tetracycline HCl
Tetracycline
Chlorhexidine diacetate
Chlorhexidine digluconate
Taurine
Iproflavone
GELS
Chitosan
HEC + polyvinylpyrrolidone
HEC + polycarbophil
Poloxamer 407 + Carbopol 934P
Glycerol monooleate + sesame oil
PLGA
Metronidazole
Tetracycline
Metronidazole
Propolis
Metronidazole
Tetracycline
MICROPARTICLE Pluronic F 127
PLGA
PLGA + PCL
Tetracycline
Tetracycline
Histatin peptides
Doxycycline
NANOPARTICLES PLGA
Chitosan oligonucleotide
Cellulose acetate phthalate
Harungana madagascariensis
leaf extract
Antisense
Thank you

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Dental Implant Drug Delivery

  • 1. DENTAL IMPLANT AS NOVELDENTAL IMPLANT AS NOVEL DRUG DELIVERY SYSTEMDRUG DELIVERY SYSTEM PRESENTED BY SUDHANSHU GANGWAR M.PHARM 1st year
  • 2. INTRODUCTIONINTRODUCTION  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.
  • 4. PERIODONTAL DISEASEPERIODONTAL 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.
  • 5. PERIODONTITIS DISEASEPERIODONTITIS DISEASE  Periodontitis is inflammation of the gingival and the adjacent attachment apparatus and is characterized by loss of connective tissue attachment and alveolar bone.  Periodontitis is a chronic bacterial infection that affects the gums and bones supporting teeth  Antibacterial agents have been used effectively in the management of periodontal infection.  The use of sustained release formulations to deliver antibacterials to the site of infection (periodontal pocket) has recently gained interest. GINGIVITIS DISEASE  Gingivitis is inflammation of the gingiva.  Gingivitis is often caused by inadequate oral hygiene. Periodontal disease can affect one tooth or many teeth.
  • 6. 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 PERIODONTAL POCKET
  • 7. PRINCIPLES AND GOALPRINCIPLES 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.
  • 8. ADVANTAGES AND DISADVANTAGESADVANTAGES AND DISADVANTAGES OF DENTAL IMPLANTOF 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
  • 9. DRUG DELIVERY SYSTEMS FORDRUG DELIVERY SYSTEMS FOR TREATING PERIODENTALTREATING PERIODENTAL DISEASESDISEASES Fibers Film  Injectable systems  Gels  Strips and compacts  Vesicular systems Microparticle System Nanoparticulate System
  • 10. FIBERSFIBERS  Fibers, or thread-like devices, are reservoir-type systems, placed into the pockets with an applicator and secured with cyanoacrylate adhesive for the sustained release of then trapped drug into the periodontal pocket.  The release of the tetracycline from the cellulose acetate fibres as occurred by diffusion mechanism is rapid with approximately 95% of the drug released in the first two hours , single application of these fibres does not provide an effective drug concentration for long periods.  Compared with the less effective tetracycline delivery from hollow fibres, fibres containing 20% (v/v) chlorhexidine, when placed into periodontal pockets, exhibited a prompt and marked reduction in signs and symptoms of periodontal disease.
  • 11. FILMSFILMS • 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.
  • 12. INJECTABLE SYSTEMINJECTABLE 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.
  • 13. GELSGELS  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.  The results indicated that an increase in carbopol concentration significantly increased gel compressibility, hardness and adhesiveness factors that affect ease of gel removal from container, ease of gel application onto mucosal membrane, and gel bioadhesion.
  • 14. INJECTABLE GELSINJECTABLE 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 .
  • 15. STRIPS AND COMPACTSSTRIPS 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 . Chitosan, a novel biodegradable natural polymer, in a gel form (1%, w/w) with or without 15% metronidazole, had demonstrated effectiveness in the
  • 16. VESICULAR SYSTEMSVESICULAR 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.
  • 17. MICROPARTICLE SYSTEMMICROPARTICLE 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.
  • 18. NANOPARTICULATE SYSTEMNANOPARTICULATE 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.
  • 19. DENTAL IMPLANT DRUG DELIVERYDENTAL IMPLANT DRUG DELIVERY DEVICESDEVICES 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.
  • 20. Preparation of Dental Implant By SolventPreparation of Dental Implant By Solvent Casting TechniqueCasting Technique
  • 21. EVALUATIONEVALUATION 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
  • 22. 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
  • 23.  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.
  • 24.  In vitro antibacterial activity: The films (size of 2x2 mm2) containing 26.6 g of drugμ 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.
  • 25. 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
  • 26. System Polymer matrix Drug Incorporated FIBERS Cellulose acetate Ethylene vinyl acetate Poly(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 HCl Chlorhexidine Chlorhexidine FILMS Ethyl cellulose Cross-linked atelocollagen Gelatin (BycoW protein) Cross-linked gelatin + glycerine Chitosan Chitosan + PLGA Metronidazole, Minocycline Tetracycline HCl Tetracycline Chlorhexidine diacetate Chlorhexidine digluconate Taurine Iproflavone GELS Chitosan HEC + polyvinylpyrrolidone HEC + polycarbophil Poloxamer 407 + Carbopol 934P Glycerol monooleate + sesame oil PLGA Metronidazole Tetracycline Metronidazole Propolis Metronidazole Tetracycline MICROPARTICLE Pluronic F 127 PLGA PLGA + PCL Tetracycline Tetracycline Histatin peptides Doxycycline NANOPARTICLES PLGA Chitosan oligonucleotide Cellulose acetate phthalate Harungana madagascariensis leaf extract Antisense