PERIODONTAL STRIPS - A NEWER APPROACH FOR SITE SPECIFIC DRUG DELIVERY FOR PERIODONTITIS

 PERIODONTAL STRIPS - A NEWER APPROACH FOR SITE SPECIFIC DRUG DELIVERY FOR PERIODONTITIS

K. I. SameerHH, Vimal Mathew 

National College of Pharmacy, Manassery, Calicut

Cite this: K. I. Sameer, Vimal Mathew, "PERIODONTAL STRIPS - A NEWER APPROACH FOR SITE SPECIFIC DRUG DELIVERY FOR PERIODONTITIS", B. Pharm Projects and Review Articles, Vol. 1, pp. 1382-1496, 2006. (http://farmacists.blogspot.in/)

INTRODUCTION

In pharmaceutical field novel and controlled drug delivery system are becoming more popular which are capable of improving patient compliance as well as therapeutic efficacy. Controlled drug delivery refers specially to the precise control of the rate by which a particular drug dosage is released from a delivery system with out the need for frequent administration¹. In general, controlled drug delivery attempts.

• To sustain drug action at a predetermined rate by maintaining a relatively constant effective drug level in the body with concominant minimization of undesirable side effects.
• Localize drug action by spatial placement of controlled release system adjacent to or in the disease tissue or organ.
• Target drug action by using carriers or chemical derivatization to deliver drug to a particular target cell type.

PERIODONTAL DISEASE

    The "periodontal diseases" is a general term of various inflammatory diseases of paradentium. The diseases include a series of diseases exhibiting various syndromes which vary from each other according to the stage or situation of the diseases or the age of the patient. the term "periodontal diseases" is given to any inflammatory disease which initially occurs at a marginal gingiva area and finally reaches an alveolar bone.

 

    The paradentitis, is characterized by remarkable symptoms such as inflammation of gingiva, formation of periodontal pockets, bleeding and pus discharge from said periodontal pockets, and it brings about resorption of alveolar bone, loose tooth, and shedding of tooth.

 

Dental infections can occur in a number of ways²

• Via the introduction of pathogens of the extra oral origin.
• Through a change in the balance of the indigenous flora
• With the entry of bacteria into normally sterile vital pulp of the tooth.

Periodontal disease refers to acute and chronic disorder of the soft tissues surrounding the teeth which eventually leads to the loss of supporting bone. These diseases occur as an inflammatory response due to the overgrowth of anaerobic organisms such as spirochetes and bacteriodes and in some cases micro-aerophillic organisms in the sub gingival plaque. These diseases if unchecked result in the destruction of the bone and soft tissues supporting the tooth.

 

The major periodontal diseases are

• mucositis,
• gingivitis,
• periodontitis and
• dental caries.

 

 

These diseases can be manifested by clinical signs such as bluish red thickned marginal gingiva, bluish red vertical zone from the gingival margin to the oral mucosa, gingival bleeding and localized pain. These are localized infections and can be treated with localized drug therapy⁵.

 

Accumulation of spirochetes loaded supra gingival plaque or food particles renders the gingiva swollen and bleed easily giving rise to gingivitis. Periodontitis is a more severe stage of periodontal disease resulting in loss of bone and collagen support of the affected tooth. It is an inflammation of the supporting tissues surrounding tooth caused by pathogenic flora established within the gingival sulcus, which later deepens to become periodontal pocket. The pocket provides ideal environment for the growth of anaerobic pathogenic bacteria such as Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, Bacteroides melaninogenicus subspecies intermedius, Eikenella corrodens, Porphyromonas gingivalis, Provetella intermedia etc⁶.

Table1.1 List of the microorganisms associated with endodontal and periodontal infections.

Aerobic and Facultative Anaerobic Bacteria

Anaerobic bacteria

Gram- positive cocci Streptococcus spp Beta-hemolytic streptococci Streptococcus milleri group (Viridans) Streptococcus mutans group* Gram-possitive bacilli Rothia dentocariosa Lactobacillus spp* Gram-negative cocco-bacilli Actinobacillus spp Actinobacillus actinomycetemcomitans Campylobacter spp Campylobacter rectus Capnocytophaga spp Eikenella spp Gram-negative rods Pseudomonas spp* Enterobacteriaceae*

Gram- positive cocci Peptortseptococeus spp Peptostreptococcus micros Gram-negative bacilli Veillonella spp Gram-positive bacilli Actinomyces spp Eubacterium spp Propionibacterium spp Lactobacillus spp Spirochtes Treponema denticola Treponema sokranskii Gram-negative bacilli Prevotella spp Prevotella intermedia Prevotella nigrescens Pophyromonas gingivalis Bacteroides spp Bacteroides forsythus Fusobacterium spp Fusobacterium

* Micro organisms associated with dental caries

Due to the invasion of these pathogenic microorganisms leads to loosening and ultimately loss of teeth. This disease affects virtually the whole world population and is a major source of tooth loss after the age of 25 years⁸.

 

TREATMENT APPROACHES

1. Conventional Periodontal therapy

    The purpose of periodontal treatment is to cure the inflammed tissue, reduce the number of pathogenic bacteria and eliminate the depth of the diseased pockets and to stop bone resorption. The conventional methods of pocket elimination are more or less mechanical and are aimed at removal of supra and mechanical plaque and degenerated and necrotic tissue lining the gingival wall of periodontal pockets through scaling, root planning and curettage⁶.

The mechanical debridement alone often leaves behind significant number of pathogens due to possible instrumentation or ability of microorganism to penetrate into deeper tissues. Inaccessibility and recolonization of pathogens can occur after scaling and root planning. With oral hygiene, a pathogenic subgingival microbial may reestablish within 42 - 60 days after a single periodontal debridement session¹⁰. Some deep periodontal pockets experience putative pathogen recolonization by
120 - 240 days despite multiple sessions of subgingival instrumentation and meticulous supra gingival plaque control⁹.

2. Antibiotic therapy

    The use of antibiotics in the treatment of periodontal diseases help to reduce or eliminate bacteria that cannot be removed by scaling and root planning. Chemotherapeutic agents can be administered systemically or locally. Tetracyclines, imidazole derivatives, fluoroquinolones etc., are the most favoured antibiotics.

Antimicrobials used to treat dental infections can be divided into two main categories, i.e., broad spectrum and narrow spectrum. Narrow-spectrum
antimicrobials include penicillin, amoxicillin, cephalexin, macrolides and tetracyclines. These drugs are having a limited antimicrobial efficacy (Table 1. 2), as they are not effective against aerobic and anaerobic betalactamase producers, as well as other specific organisms¹¹.

 

Table 1. 2 Susceptibility of infective microorganisms to the major antimicrobials.

	Penicillnn	Oxacillin	Amoxicillin	Cef/1	Macrolides	Clindamycin	Metronidazole	Tetracycline	Levofloxacin	Gatifloxacin
Aerobic bacteria
Streptococcus Group A	+	+	+	+	+	+	0	A+	+	+
Streptococcus spp	+	+	+	+	+	+	0	+	+	+
Staphylococcus spp	0	+	+	+	+	+	0	A+	A+	+
Capnocytophaga spp	+	+	+	A+	A+	+	0	+	+	+
Eikenella spp	+	0	+	0	A+	0	0	+	+	+
Anaerobic bacteria
Peptostreptococcus spp	+	+	+	+	+	+	A+	A+	A+	+
Actinomyces spp	+	+	+	+	+	+	+	A+	+	+
Prevotella spp	+	A+	+	0	0	+	+	A+	A+	A+
Porphyromonas spp	A+	A+	+	0	0	+	+	A+	0	A+
Fusobacterium spp	A+	A+	+	0	A+	+	+	A+	0	A+
Bacteorides spp	A+	A+	+	0	0	+	+	A+	0	A+

A +: higher activity towards organisms

+: Moderate activity

0: No activity

Cef/1 – first generation cephalosporins

 

    Systemic periodontal antimicrobial therapy is based on the premise that specific microorganism cause destructive periodontal disease and that the antimicrobial agent in the periodontal pocket can exceed the concentration necessary to kill the pathogens. Systemic antibiotics can reach microorganisms at the base of deep periodontal pockets and furcation areas via serum and may also affect organisms residing within gingival epithelial and connective tissue. With systemic antibiotic therapy there is a considerable variability in the therapeutic activity due to factors like poor absorption in the gastrointestinal tract, first pass metabolism, systemic distribution, bacterial sensitivity and resistance¹².

 

    Some studies also report poor results due to the fact that the active product does not reach in adequate concentration at the site of action, as it is not retained locally for sufficient period of several thousand folds before it reaches the site of action necessitating ingestion of large doses.

 

    The increased toxic effects of these elevated dose levels makes systemic administration unacceptable due to low benefit to risk ratio. Repeated long term use of systemic antibiotics is fraught with potential danger including resistant strains and super infections¹⁵.

 

    These draw backs can be markedly reduced if antimicrobial agent to be used locally. Because of the smaller dosage used and topical chemotherapy is much safer than systemic chemotherapy in avoiding the side effects of antibacterial agents¹⁶.

 

3. Local Drug Delivery

    Local applications (as mouth rinse, gels, tooth paste etc,) control only supra gingival microbial plaque or periodontal disease involving pocket formation and also requires high initial concentrations and multiple applications in order to provide sustained effectiveness ¹⁷. Local application of antibiotics has been achieved either by sub gingival irrigation or by incorporating the drug into different devices for insertion into periodontal pockets . Many drugs like chlorhexidine, tetracycline are tried as mouth rinses in the treatment of periodontal diseases. In-spite of its superior effects, chlorhexidine does not reach the periodontal pocket when administered as mouth rinse. Subgingival irrigation of antimicrobial involves local drug delivery but not controlled release.

 

    Local drug delivery devices are of two types. In the first type, the drug delivery system is designed to deliver agent locally in the periodontal pocket but without any mechanism to retain therapeutic levels for a prolonged period of time. Such devices generally exhibits exponential increase and decrease in drug concentration at the site¹⁸.

 

    Second type is the controlled release local drug delivery devices which may secure antimicrobial effect for a prolonged period of time at the diseased site, than that can be achieved by systemic or local topical applications and also by passes the systemic complications¹⁹.

 

    The controlled release delivery of antimicrobials directly into periodontal pocket has received greatest interest and appears to hold some promise in periodontal therapy. These delivery systems are produced by immobilizing antibiotic and antimicrobial agents with a carrier substance to provide controlled local release.

 

    Local antimicrobial therapy in periodontitis involve direct placement of antimicrobial agents into subgingival sites minimizing the impact of the agents on non oral body sites. Local antimicrobial agents may be personally applied as a part of home care oral hygiene regimens and/or professionally applied as part of clinic based treatment procedures. Local antimicrobial therapy in periodontitis may be further classified as providing either non-sustained or sustained subgingival drug delivery. Non-sustained subgingival drug delivery provides high pocket concentrations of the antimicrobial agent over an extended time period within periodontal pockets. Controlled drug release can be provided with subgingival irrigation of an agent intrinsically substantive for both tooth surfaces or pocket placement of commercial antimicrobial fibres, gel or films. The potential application of these new concepts to periodontology and the treatment of periodontal infections was championed and developed into a viable concept primarily by Dr. J. Max Goodson²⁹.

 

LOCAL ANTIMICROBIAL AGENT POCKET DELIVERY

Distinct Advantages of Local Controlled Release Devices

• It is useful in controlling and monitoring the desired drug levels in the site.
  

• It allows local modification of tissue permeability inhibit protease activity or decrease immunogenic response.
  
• It is a useful means of delivery of drug to the oral cavity that is not absorbed into the gastro intestinal system (e.g. chlorhexidine).
  
• It bypasses hepatic first pass metabolism, therapy offering a greater bioavailability and reduction in dosage²³.
  
• The drug escapes the acidic environment of the stomach.
  
• Therapeutic serum concentrations of the drug can be achieved more rapidly
  .
• Sustained release drugs offer a one time application has an advantage over repeated application.
  

Disadvantages:

• There is difficulty in placing therapeutic concentrations of antimicrobial agent into deeper parts of periodontal pockets and furcation lesions.
  
• Personal application of antimicrobial agent by patients lack of adequate manual dexterity, limited understanding of periodontal anatomy and poor compliance and performance with recommended procedures.
  
• The task of professionally applying local antimicrobial agent in periodontitis patients with numerous advanced lesions distributed through out their mouth is time consuming and labor intensive.
  
• Antimicrobial agents locally applied into periodontal pockets do not markedly affect periodontal pathogens residing with in adjacent gingival connective tissues and on extra-pocket oral surfaces, which increases the risk of later reinfection and disease recurrence in treated areas.
  

 

Success of any drug system designed to target periodontal infection depends upon its ability to deliver the anti-microbial agent to the base of pocket at a bacteriostatic or bactericidal concentration. It must also facilitate retention of medicament long enough to ensure an efficacious result. Commonly used techniques²⁴ to administer antimicrobial with regard to attaining these criteria are compared in Table 1. 3.

Table 1. 3. Comparison of drug delivery systems for management of periodontitis

	Mouth Rinse	Subgingival Irrigation	Systemic delivery	Controlled delivery
Reaches site of disease and activity	Poor	Good	Good	Good
Adequate drug concentration	Good	Good	Fair	Good
Adequate duration of therapy	Poor	Poor	Fair	Good

 

    Local antimicrobial therapy in periodontitis involves direct placement of an antimicrobial agent(s) in to subgingival sites, minimizing the impact of the agent(s) on non oral body sites.

 

Types of local antimicrobial agent therapy in periodontal diseases include.

1. Personally applied (in-patient home self care)

1. Non-sustained subgingival drug delivery (home oral irrigation)

1. Sustained subgingival drug delivery (Not developed to date)

2. Professionally applied (in dental office)

1. Non sustained subgingival drug delivery (Professional pocket irrigation)
2. Sustained subgingival drug delivery (Controlled release devices)

Controlled drug delivery systems are designed to deliver the drug slowly for prolonged periods for sustaining drug action. These dosage forms are commonly reffered as sustained-release, controlled-release, timed-release and slow release. These technologies assure therapeutic concentrations of the antimicrobial agents in the subgingival area, atleast for 3 days following a single application. Most controlled release devices for periodontal application are polymer based, with diffusion of drugs across a rate controlling membrane.

 

CONTROLLED RELEASE LOCAL DELIVERY DEVICES

    These devices employ the controlled release technologies to assure therapeutic concentrations of the antimicrobial in the sub gingival area for at least 3 days following a single application.

Different types of controlled release local delivery devices fall into following groups

1. Reservoir devices (membrane diffusion systems)

This includes dialysis tubing 3-5 mm long, 0.2 mm wide containing a core of drug solution. which is left in the pocket for a week. Reservoir devices that lack rate control include hollow fibres, gels and dialysis tubing. These systems tend to release chemotherapeutic agents very quickly and only marginally qualify as sustained release devices. The problems associated with these devices are, irritation of the pocket, premature loss from the pocket and rapid drug release²⁷.

 

1. Monolithic devices

Bio absorbable, biodegradable materials can be left in situ. This eliminates the risk of disturbing a site after therapy. The controlled release local delivery devices (monolithic) are usually polymers (films/fibres) containing homogeneously dissolved or dispersed drug.

In these devices, the drug is dispersed in a solid polymer matrix, Examples include acrylic strips and ethylene vinyl acetate (EVA) fibres. Acrylic strips are typically 0-2 mm thick. Treatment is carried out over 2 - 4 weeks, with a replacement of new strips inserted each week. Drug release occurs over a period of 10 - 14 days. Strips tend to be lost from the pocket. This can be avoided by applying periodontal dressing. Other monolithic devices include strips made of ethyl cellulose (EC), poly ethylene glycol (PEG), Hydroxy propyl methyl cellulose (HPMC) and cross linked collagen films²⁷.

 

The two basic types are

1. Fixed monolithic devices: Where the polymer maintains its integrity as the drug is lost.
2. Erodable monolithic devices: Which breaks up as the drug is released.

If the drug is present as dispersion, the release will be proportional to the square root of time and if the drug is present only dissolved in the constant release rates, then decay exponentially. It is possible to obtain more constant release rates by increasing the concentration of drug towards the center of the monolithic core to produce a laminated device. The various polymers used for the monolithic device are ethylene vinyl acetate co-polymer, ethyl cellulose, methyl methacrylate, poly ethylene-2 hydroxy ethyl methylacrylate, poly (ortho esters), atellocollagen etc.

The device should be designed for rapid insertion and to minimize the pain and discomfort to the patient. The monolithic devices can be prepared conveniently by using simple polymer fabrication techniques.

1. Melt fabrication Technique
   

Films can be produced by extrusion in to thin film. Another process known as calendaring, where the polymer is squeezed between heated rollers to form film²⁷.

1. Solution casting

The polymer is dissolved in a suitable solvent to form a viscous solution, which is then spread on flat non-adhesive surface and the solvent is allowed to evaporate. The resultant film is peeled from the surface.

1. Polymerisation In situ

A liquid polymer or pre polymerized inside a suitable mould. The release from monolithic devices depends on diffusion of drug through matrix. By manipulating the system, selecting the ideal polymer, adjusting the cross-linking, fillers, plasticizers and by using co-polymers, release of some low molecular drug can be achieved.

    For an antimicrobial agent to be successful the pathogen must be known, it must be susceptible to the drug. It should not readily develop resistance for an adequate period of time. Also the drug should have little or no side effects ²⁹.

 

MECHANISMS OF DRUG RELEASE

    The release of drug from a localized drug delivery system can be achieved by the following mechanisms.

1. Pure diffusion
2. Chemical reactions
3. Counter-current diffusion
4. Externally imposed controls

Controlled release polymeric systems can be classified on the basis of the mechanism controlling the release of the incorporated drug.

 

DIFFUSION CONTROLLED SYSTEMS

a) Reservoir systems

    In these systems, core of the drug is surrounded by a swollen or non swollen polymer film and diffusion of the drug through the polymer is the rate limiting step. Reservoir devices are also of two types. Reservoir without a rate controlling system. Reservoirs that lack rate control include hollow fibres, gels and dialysis tubing. Reservoirs with rate controlling systems include erodable polymeric matrices, polymer membranes, monolithic matrices and coated particles³².

b) Matrix systems

    In these systems, the drug in uniformly distributed throughout a solid polymer. The drug diffusion through the polymer matrix is the rate limiting step.

 

CHEMICALLY CONTROLLED SYSTEMS

a) Bioerodable system

    In these systems, a drug is uniformly distributed throughout the polymer, and the drug is released by diffusion as the polymer phase decreases with time. As the polymer surrounding the drug resorbed, the drug escapes.

b) Pendant chain system:

    In these systems, the drug is chemically bound to a polymer back bone and drug release occurs via hydrolytic or enzymatic cleavage.

 

 

PERIODONTAL STRIPS

    A pharmaceutical composition which is applied to a periodontal pocket or paradentium for the purpose of treating periodontal diseases. The pharmaceutical composition, which is provided in the form of gel, sheet, film or bar-like formulation, releases a controlled and effective amount of an active ingredient at the periodontal pocket or paradentium.

 

    Strips which comprise polymers and active ingredients for treatment of periodontal diseases have been developed. These strips are said useful for the treatment of plaques and inflammation beneath the gingival margin. The strips can be applied directly to the lesional region to be treated, and therefore, the active ingredient can be concentrated to the desired site selectively. This modified therapeutic method has been proved to be more effective than any conventional pharmacotherapy.

 

    The formulations comprise a mixture of an active ingredient and a homogeneous polymer base. Accordingly, where such formulation is designed to contain two or more active ingredients which differ from each other in terms of pharmacological activity and therapeutically effective dose, it has been impossible to prepare the formulation in which each of the plural ingredients may release independently and provide its suitable concentration as desired. The strip which comprises a soluble polymer as a base or carrier permits a rapid release of an active ingredient.

Carrier consists of:

(A) Water soluble polymer, and

(B) Polymeric particles having a limited solubility,

 

Polymers used

    Insoluble polymer are ethyl cellulose, cellulose acetate, ethyl methacrylate / trimethylammonioethyl methacrylate chloride copolymer, and the like.

     The sparingly soluble polymer includes, for instance, biodegradable polymer such as polyglycolic aicd, polylactic acid, polytetramethylglycolide, polydiethylglycolide, poly-caprolactone, poly (DL-decalactone), poly (alkyleneadipate), copolymers thereof, and ion exchange resins.

 

    Soluble polymer are, methyl cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, sodium alginate, propylene glycol alginate, pulluran, tragacanth, xanthan gum, chitosan, polyethylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, and a salt.

 

Drugs commonly employed

    Some therapeutic agents which are amenable to delivery by this means and are potentially of value for periodontal therapy, include (but are not limited to) antimicrobial/antibacterial agents such as iodine, sulfonamides, mercurials, bisbiguanides, or phenolics; antibiotics such as tetracycline, neomycin, kanamycin, metronidazole, or clindamycin; antiinflammatory agents such as aspirin, naproxen, ibuprofen, flurbiprofen, indomethacin, eugenol, or hydrocortisone; immune-suppressive or stimulatory agents such as methotrexate or levamasole; dentinal desensitizing agents such as strontium chloride or sodium fluoride; odor masking agents such as peppermint oil or chlorphyll; immune reagents such as immunoglobulin or antigens; local anesthetic agents such as lidocaine or benzocaine; nutritional agents such as amino acids, essential fats, and vitamin C; antioxidants such as alphatocopherol and butylated hydroxy toluene; lipopolysaccharide complexing agents such as polymyxin; or peroxides such as urea peroxide

 

Optional Components

    In addition to the drug active, the compositions/devices of the present invention may include a variety of optional components. Such components include, surfactants, other polymers, viscosity controlling agents, complexing agents, antioxidants, gums such as guar gum, waxes/oils such as castor wax, castor oil, glycerol, dibutyl phthalate and ethyl sebacate as well as many others.

 

    The additional polymer may include a number of polymers such as methyl cellulose, polycaprolactone and polylactide. A particularly preferred polymer is a copolymer of lactide and glycolide. The molecular weight lies in the range of from about 1000 to about 120,000 (number average).

 

    If used, these optional components comprise from about 0.1% to about 50%, preferably from about 0.5% to about 25% of the total composition/device.

 

Method of preparation

    One or more of non-soluble polymers is dissolved, as the first step, in an appropriate organic solvent. To the resultant solution is dissolved or dispersed one or more of active ingredients, and the mixture is formed into film or sheet by casting method. The resultant solid material is ground into particles.

    The average particle size may range from 1.mu. to 500.mu. Depending on the contemplated release pattern of the active ingredient. However, the size between 1.mu. and 303.mu. is generally preferred.

 

    The film or sheet may also be prepared by compression molding, extrusion or calendering. The most suitable forming process among others is selected depending on the physico-chemical properties of the polymers employed.

 

    The convenient size of the film or sheet may be 0.1-0.5 mm in thickness, 0.5-3 mm in width, and 10-50 mm in length. The size of the bar may generally range from 0.5 to 1.5 mm in diameter and from 10 to 50 mm in length. Furthermore, the composition may be cut in suitable size by the user depending on several factors, such as severity of the disease, and the width and depth of the locus to be applied. The composition can be applied to the periodontal pocket or paradentium by insertion, injection, or rubbing according to the type of formulation.

Example
1

Poly(lactic acid) (10 parts) and tetracycline hydrochloride (2 parts) are dissolved in methylene chloride (100 parts). Flow casting of the resultant mixture yields a sheet, which is ground into particles having an average size of 50.mu.

The particles (10 parts) and hydroxypropyl cellulose (10 parts) are uniformly admixed. The mixture is blended with water, extruded with pressure, and dried. The bar-like shaped product of 1.0 mm diameter is thus obtained.

 

Example 2

    Methacrylic acid / methyl methacrylate copolymer (1:2 molar ratio) (80 parts) is dissolved in ethanol (1000 parts). In the solution are suspended or dissolved indomethacin (5 parts) and triacetin (20 parts), and the mixture is casted into a sheet, which is then pulverized into particles having an average size of 80.mu.

    Hydroxypropyl cellulose (10 parts) is dissolved in water (1000 parts), and tetracycline (25 parts) is added to the resultant solution, after adjusting to pH 6.0 by addition of hydrochloric acid. The resultant mixture (80 parts) are uniformly admixed with the particles obtained above (20 parts) to yield the product in a gel form.

 

METHOD AND MATERIALS

(1) Preparation of Sample

Methacrylic acid / methyl methacrylate copolymer (1:2 molar ratio) (80 parts) was dissolved in ethanol (1000 parts). Triacetin (20 parts) and tetracycline hydrochloride (6 parts) were then mixed with the resultant solution. The mixture was casted on a Teflon tray and dried at 40.degree. C. The resultant sheet was pulverized into particles of 105.mu. to 177.mu. in size.

    On the other hand, hydroxypropyl cellulose (viscosity of 2% aqueous solution is 1000 to 4000 cp at 20.degree. C.) (one part) was dissolved in water (99 parts). In the solution was dissolved tetracaine hydrochloride (0.03 part).

    The hydroxypropyl cellulose solution and the particles are uniformly admixed at a weight ratio of 100:0.5, and the mixture is deaerated, casted on a Teflon tray with care to ensure the constant thickness, and air-dried to yield a film having 300.mu. thickness.

    In a solution of hydroxypropyl cellulose (1 part) dissolved in water (100 parts) were dissolved tetracycline hydrochloride (0.02 part) and tetracaine hydrochloride (0.02 parts), and the mixture was adjusted to pH 6, deaerated, casted on a Teflon tray, air-dried to obtain a film having 300 thickness.

Example
The following is an exemplary composition/device ______________________________________
Weight %
______________________________________
Tetracycline hydrochloride
50
Polypropenoic acid 22.7
Poly(lactyl-co-glycolide)/50:50 copolymer
22.7
Propylene Carbonate 4.6
______________________________________

 

    The above composition can be prepared in a number of different ways. One way is as follows: Polymer is charged into 110.degree. C., electrically heated mixer, equipped with high shear Sigma type rotor blades. Propylene carbonate is added and mixed into the polymer. The drug is added and mixed until uniform. The drug polymer blend is removed for further processing into desired size and shaped devices.

 

    Once a strip is placed in periodontal cavity, the polymer swells, expands, and reaches narrow crevices and furcations of the treated cavity, carrying active agent throughout the cavity. This provides most desirable efficacy at treatment site.

 

 

CONCLUSION

    One of the most persistent problems faced by the formulation technologist is that many drugs do not reach the receptors in the therapeutic concentrations intended. By the development of novel drug delivery systems, a more site specified and controlled drug delivery systems was made possible and due to the very same reason a reduction in the dose and dosing can be accomplished. This may inturn result in minimizing side effects and a better patient compliance.

 

    This approach is being applied treatment of periodontitis, where by the antimicrobial agents can be directly administered to the periodontal pocket and thus inhibit the growth of pathogenic bacteria. This site specific delivery of drug can thus overcome the disadvantages faced during systemic administration of antimicrobials for periodontitis, where the drug get diluted many times before it reaches the site of action. Thus a controlled release local delivery system formulated using biodegradable polymers will be most efficient in treatment of periodontitis.

 

 

BIBLIOGRAPHY

1. Sunil Agarwal, Venkatesh M, Udupa N. Controlled drug delivery systems for periodontitis. The pharma review 2004, Jul-Aug; 2 (11): 61-82.
2. Rubin's pathology: Clinicopathologic foundations of medicine. 4^th ed Philadelphia: Lippincott Williams and Wilkins; 2004: 1276-79.
3. Agarwal RK, Robinson DH, Maze G, Reinhardt RA. Development and characterization of Tetracycline (Polylactide glycolide) films for the treatment of periodontitis. J Control Release 1993; 23:137-146.
4. Fermin A Carranza, Michel G. New man. Clinical periodontology. Prism books Pvt. Ltd., New Delhi; 1996: 281-82.
5. Jain NK. Controlled and novel drug delivery 1^st edition, New Delhi CBS Publication; 1997: 130-147.
6. Roskos KV, Fritzinger BK, Armitage GC, Heller. Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly (orthoesters). Biomaterials 1995; 16:313-317.
7. Deasy PB, Augusta EM, Collins, Maclarthy DJ, Russel RJ. Use of Strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. J Pharm Pharma Col. 1989;41:694-99.
8. Sbordone L, Ramaglia L, Gulleta J. Recolonization of subgingival microflora after scaling and root planning in human periodontitis. J Periodontal 1990; 61: 579-584.
9. Magnusson I, Lindhe J, Yoneyamma T, Lilzenberg B. Recolonization of subgingival microbials following scaling in deep pockets. J Clin Periodontal 1984; 11:193-207.
10. David LJ, Sebastian C. Antimicrobial and other chemotherapeutic agents in periodontal therapy. Chapter 14 in Fermin A. Carranza and Michael G. Newman. Clinical Periodontology. Prism books Pvt. Ltd., New Delhi; 1996; 511-13.
11. Muller HP, Eickholz P. Heineke A, Pohl S, Muller RF, Lange DE. Simultaneous isolation of Actinobacillus actinomycetecomitans from subgingival and extracervicular locations of the mouth. J Clin. Periodontol 1995;
    22: 413-419.
12. Muller HP, Lange DE, Muller RF. Failure of adjunctive minocycline HCl to eliminate oral Actinobacillus actinomycetemcomitans. J Clin Periodontol 1993; 20: 498-504.
13. Rahman S, Ahuja. A, Ali. J, Khar RK. Site Specific delivery systems for the treatment of periodontitis. Indian J Pharm Sci, 2003; 65(2): 106-112.
14. Steinberg D, Freidman M, Soskolne A, Sela MN. A new degradable controlled release device for treatment of periodontal disease: Invitro release study.
    J Periodontal 1990; 61: 393-398.
15. Yamagami H, Takamori A, Sakamoto T, Okuda M. J Periodontal 1992
    (63), 2-6.
16. Eckles TA, Reinhardt RA, Dyer JK, Tussing GJ, Szydlowski WM, Du Bois LM. Intracervicular application of tetracycline in white petroleum for the treatment of periodontal disease. J Clin Periodontal 1990; 17: 454-462.
17. Freidman M, Steinberg D. Sustained release delivery systems for treatment of dental diseases. Pharm. Res. 1990; 7: 313-317.
18. Larsen T. Invitro release of doxycycline from bioabsorbable materials and acrylic strips. J Periodontal 1990; 61: 30-34.
19. Korman KS. Controlled release local delivery antimicrobial in periodontitis: Prospects of the future. J Periodontal 1993; 64: 782-91.
20. Finkelman RD, Williams RC. Local delivery of chemotherapeutic agents in periodontal therapy:Has it's time arrived. 1998; 25: 943-946.
21. Robinson JR, Vincent HL, Lee. Controlled drug delivery, Fundamentals and applications. 2^nd ed: Marcel Dekker; 1987; 159-163.
22. Tonet MS. Local delivery of tetracycline: from concept of clinical application. J. Clin Periodontal 1998; 25: 969-977.
23. Venkateshwari Y, Jayachandra RB, Sampath Kumar D, Mittal N, Pandit JK. Development of low cost tetracycline strip for long term treatment of periodontal.
24. Ramesh D, Vijaya, Sehgal DK.Biological activity and theraputic applications of collagen. Indian drugs 2000;37(3).
25. Pharmacopoeia of India, 1996, Vol II, 3^rd edition, A-143.
26. Dental infections: www.medceu.com / course-no9.17.2004

1. http..//www.bms.com.Tequin prescribing information

 

 

Cite this: K. I. Sameer, Vimal Mathew, "PERIODONTAL STRIPS - A NEWER APPROACH FOR SITE SPECIFIC DRUG DELIVERY FOR PERIODONTITIS", B. Pharm Projects and Review Articles, Vol. 1, pp. 1382-1496, 2006. (http://farmacists.blogspot.in/)