Title of Invention	COMPOSITION FOR LOCAL DELIVERY OF MEDICINES FOR PERIODONTITIS & METHOD FOR PREPARATION OF THE SAME
Abstract	The present invention relates with pharmaceutical composition for the treatment of periodontal diseases e.g. periodontitis. The composition to be applied directly into the periodontal pocket where it is supposed to give extended drug release for longer time. In particular this invention relates to a process for making formulation for local delivery of active pharmaceutical substance for the treatment of periodontitis. Active may be selected from antibacterial, antibiotic, local anaesthetic or anti plaque and other as like with or without combination. Periodontitis (peri - around, odont = tooth, -itis = inflammation) refers to a number of inflammatory diseases affecting the periodontium- that is, the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by bacteria that adhere to and grow on the tooth"s surfaces, along with an overly aggressive immune response against these bacteria. Most of the bacteria causing periodontitis includes anaerobic gram-negative bacteria in the subgingival area are Actinobaci-llusactinomycetemcomitans (Aa), Porphyromonas gingivalis, (Pg), Prevotella intermedia (Pi), and Tannerella forsythensis (Tf). These bacteria secrete colagenase that degrades periodontal ligament, connective tissue of the periodontal membrane. As a result periodontal membrane is separated and periodontal pocket is formed. Periodontitis can be diagnosed by inspecting the soft gum tissues around the teeth with a probe and radiographs by visual analysis, to determine the amount of bone loss around the teeth. The removal of the periodontal plaque is the primary treatment for periodontitis. The plaque can be removed with the use of chemotherapy or by root planning and scaling called apparatotherapy. There are lots of problem associated with root planning and scaling e. g. instruments can"t reach the area where bacteria used to stay, anatomical arrangement of the teeth restricts effective root planning & scaling. The only option remains is the chemotherapy.

Title of Invention

COMPOSITION FOR LOCAL DELIVERY OF MEDICINES FOR PERIODONTITIS & METHOD FOR PREPARATION OF THE SAME

Abstract

The present invention relates with pharmaceutical composition for the treatment of periodontal diseases e.g. periodontitis. The composition to be applied directly into the periodontal pocket where it is supposed to give extended drug release for longer time. In particular this invention relates to a process for making formulation for local delivery of active pharmaceutical substance for the treatment of periodontitis. Active may be selected from antibacterial, antibiotic, local anaesthetic or anti plaque and other as like with or without combination. Periodontitis (peri - around, odont = tooth, -itis = inflammation) refers to a number of inflammatory diseases affecting the periodontium- that is, the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by bacteria that adhere to and grow on the tooth"s surfaces, along with an overly aggressive immune response against these bacteria. Most of the bacteria causing periodontitis includes anaerobic gram-negative bacteria in the subgingival area are Actinobaci-llusactinomycetemcomitans (Aa), Porphyromonas gingivalis, (Pg), Prevotella intermedia (Pi), and Tannerella forsythensis (Tf). These bacteria secrete colagenase that degrades periodontal ligament, connective tissue of the periodontal membrane. As a result periodontal membrane is separated and periodontal pocket is formed. Periodontitis can be diagnosed by inspecting the soft gum tissues around the teeth with a probe and radiographs by visual analysis, to determine the amount of bone loss around the teeth. The removal of the periodontal plaque is the primary treatment for periodontitis. The plaque can be removed with the use of chemotherapy or by root planning and scaling called apparatotherapy. There are lots of problem associated with root planning and scaling e. g. instruments can"t reach the area where bacteria used to stay, anatomical arrangement of the teeth restricts effective root planning & scaling. The only option remains is the chemotherapy.

Full Text	FORM - 2 THE PATENTS ACT, 1970 (39 OF 1970 ) COMPLETE SPECIFICATION (Section -10, rule 13) "COMPOSITION FOR LOCAL DELIVERY OF MEDICINES FOR PERIODONTITIS & METHOD OF MAKING THE SAME" Dr. Vishnu. K. Mourya, An Indian National Of Government College of pharmacy, Vedant road, Osmanpura, Aurangabad-431 005 (MH). The following specification particularly describes the nature of the invention and the manner in which it is to be performed. The present invention relates with pharmaceutical composition for the treatment of periodontal diseases e.g. periodontitis. The composition to be applied directly into the periodontal pocket where it is supposed to give extended drug release for longer time. In particular this invention relates to a process for making formulation for local delivery of active pharmaceutical substance for the treatment of periodontitis. Active may be selected from antibacterial, antibiotic, local anaesthetic or anti plaque and other as like with or without combination. Periodontitis (peri - around, odont = tooth, -itis = inflammation) refers to a number of inflammatory diseases affecting the periodontium- that is, the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by bacteria that adhere to and grow on the tooth's surfaces, along with an overly aggressive immune response against these bacteria. Most of the bacteria causing periodontitis includes anaerobic gram-negative bacteria in the subgingival area are Actinobaci-llusactinomycetemcomitans (Aa), Porphyromonas gingivalis, (Pg), Prevotella intermedia (Pi), and Tannerella forsythensis (Tf). These bacteria secrete colagenase that degrades periodontal ligament, connective tissue of the periodontal membrane. As a result periodontal membrane is separated and periodontal pocket is formed. Periodontitis can be diagnosed by inspecting the soft gum tissues around the teeth with a probe and radiographs by visual analysis, to determine the amount of bone loss around the teeth. The removal of the periodontal plaque is the primary treatment for periodontitis. The plaque can be removed with the use of chemotherapy or by root planning and scaling called apparatotherapy. There are lots of problem associated with root planning and scaling e. g. instruments can't reach the area where bacteria used to stay, anatomical arrangement of the teeth restricts effective root planning & scaling. The only option remains is the chemotherapy. The antibiotics like amoxicillin, doxycyclin, minocycline etc are effective in periodontitis. The chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole etc can be used as antibacterial agents. In addition to the bacterial infection, patients suffer with pain & inflammation of gingiva the present invention will be useful in all these conditions. Local anaesthetics like lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or their salts help to reduce pain associated with periodontitis. Improvement over known art: The method by which a drug is delivered can have a significant effect on its efficacy. The most of the available therapies for periodontitis include systemic delivery of antibacterial or antibiotic. When administered systemically many drugs don't have an optimum concentration range within which maximum benefit is derived, thus delivery of these drugs can be toxic or produce no therapeutic benefit at all. On the other hand, the very slow progress in the efficacy of the treatment of periodontitis has suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to target in tissues. From this, new ideas on controlling the pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, biorecognition, and efficacy of drugs were generated. Thus, present work utilizes new strategies, often called drug delivery systems (DDS) based on interdisciplinary approaches that combine polymer science, pharmaceutics, bioconjugate chemistry, and molecular biology. Here we are aiming to minimize drug degradation and loss, prevention of harmful side- effects and to increase drug bioavailability arid the fraction of the drug accumulated in the required zone by focusing on local drug delivery and drug targeting systems having extended release effect. The area defects or hardships in the prior art; The well-known method in the treatment of periodontitis is effective removal of biofilm or periodontal plaque by means of scaling & root planning (RPS). However despite biofilm removal patients still feel ongoing loss of attachments. One possible explanation for this clinical finding may be the inability of therapy to suppress periodontal pathogens to levels that are compatible with persistent periodontal health Chemotherapy for periodontitis may be systemic or local. In systemic administration there is rapid declination in plasma drug concentration below therapeutic level. Thus, large dose of drug is required to maintain the drug concentration for its effective action. The large dose may lead to sideffects like hypersensitivity, gastrointestinal intolerance and drug interactions with alcohol and subsequent resistance to antibiotics. Thus during this therapy resistant bacterial strains may develop & normal bacterial flora may get eradicated. Thus local drug delivery may be a solution. But because of continues saliva flow, movement of tongue, lubricated oral soft tissues, and dislocating action from chewing food and drinking, locally administered drug may not able to achieve & maintain the required concentration at site to achieve therapeutic efficacy and limit side effects To overcome these problems there is need to develop technique to deliver drug at affected site with maintaining required concentration within therapeutic window for extended period- Actisite is the first subgingival DDS introduced both in the USA and Europe consists of fibers of ethylene vinyl acetate containing tetracycline. Actisite has extended release of tetracycline over a 10-day period. As it possesses lack of biodegradability it needs to be removed after treatment which diminishes its importance. Elyzol and dentomycin dental gels have most resorbable polymers like polycaprolactone, such as that used to degrade rapidly and most of the drug is released within 24 hr. The polycaprolactone is the biodegradable polymer releases 100% of the drug load within 24 hr, also its high cost to use it in potential applications renders it to least priority for use in dental gel thus it may not be used for extended release formulation. Another subgingival DDS exhists, which consists of a two part liquid system containing doxycycline hyelate as an active agent. Poly (lactide) is used as polymer with n- methyl pyrrolidone as a solvent. Here, poly (lactide) is having advantage as it gets precipitated as it comes in contact with water leading to extended release effect. One formulation is developed using cellulose acetate hallow fiber in which drug is intrapped. As the formulation is in the form of fiber, it need to be cut in to the length for dosage & it need to coil around the teeth, then push into periodontal pocket for better effect. Thus it revealed that method is inconvenient to administer drug into periodontal pocket. According to EP A1 244118, PLGA microspheres with tetracycline are dispersed in Pluoronic gel & this formulation proposed to insert in periodontal pocket. The similar preparation also exists with minocycline. The formulations with these microspheres has disadvantage that as microspheres has hydrolytic property being made up from gel can not last for longer time period. Thus formulation is inconvenient for extended release therapy for periodontitis. From above description & literature sited for therapies for periodontitis, it is clear that no method is available which can deliver drug effectively at the site for extended period continuously having biodegradability with patient compliance in relation with dosing, cost and frequency of administration. The present inventor took lots of trials for development of effective formulation for periodontitis aiming to have local administration, extended release effect with maintaining effective drug concentration continuously for eight days having patient convenience in relation to administration, dosing & cost. By taking continuous trials for perfect formulation for periodontitis inventor came to conclusion that if the drug is entrapped in the gel prepared by using non aqueous solvent and biodegradable polymer which is supposed to get polymerized as soon as it get in contact with saliva. As the polymer is degraded slowly the polymerized matrix will release the drug continuously for extended period without interference of any external parameter. Summary of invention: The present invention relates to locally administrable biodegradable and extended release pharmaceutical composition and process for preparation & filling thereof. The composition is to be administered directly in to periodontal pocket with the help of volume marked syringe. The composition is in the form of non-aqueous gel made with biodegradable polymer having property to form polymer matrix as soon as it gets contact with water. In addition present invention provides process for preparing a composition comprising the steps making the gel containing biologically active substance & filling the gel in syringes. Detailed description of the invention: The physiologically active substance which can be used for treating periodontitis contains antibiotics, antibacterials, local anaesthetics, antiinflammatory analgesics & steroids. Antibiotics which can be used in present invention may be minocycline, tetracycline, oxytetracycline, tetracycline, amoxicillin, ampicillin, erythromycin, clarithromycin, azithromycin, bacitracin, kitasamycin, spiramycin & salts thereof or any other which can be used in periodontitis. The antibacterials or antifungals which can be used in present invention may be chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole & salts thereof or any other antibacterial/antifungal effective in periodontitis.. Local anaesthetics like lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or salts thereof & anti-inflammatory analgesics like diclifenac, flubipriofen, ketoprofen, ibuprofen, mafenamic acid, aspirin, paracetamol & salts thereof or any other which help to reduce pain associated with periodontitis. The biodegradable polymer used in preparation of gel is phthalate derivatives like hydroxyl propyl methyl cellulose phthalate, cellulose acetate phthalate which can be absorbed into body. The concentration of polymer is having important effect on the drug release. Thus by optimizing concentration of polymer we can control the release time of drug. The non aqueous solvent used for preparing gel is N - methyl pyrrolidone. It is having additional effect of drug permeation enhancer which will help to increase the applicability of formulation. The polymer 85 solvent used here is harmless to human body. The gel is filled in syringe can be inserted directly into the periodontal pocket where on contact with water a polymer matrix is formed which lead to extended release of drug. The following steps explains the process of making the gel 1) Dissolve the polymer in the N-methyl pyrrolidone to form the clear gel. 2) Step of making entrapment of drug in to gel. 3) Step of filling gel into volume marked syringe. Step 1): The polymer hydroxyl propyl methyl cellulose phthalate is dispersed in N- methyl pyrrolidone with continuous stirring. The desirerable concentration of polymer used is between 10-to 25 % w/v. The concentration depends on the desired drug release required. The stirring continued until the clear gel is formed. Step 2): The drug is ensured of having moisture less than 0.05%. The drug used is added slowly in formed gel with continuous stirring. The uniform mixing is ensured by observing clear gel having faint yellow color. The drug concentration is used in the range of 10- 40% w/v depending on type of action required e. g. antibacterial or analgesic. The following examples can explain the applications of present invention. But the claims of the present invention are not limited within these examples. The preparation example 1: The preparation of the biodegradable dental gel using antifugals. The 16.7 gm of hydroxyl propyl methyl cellulose phthalate was dissolved in 70 ml of n-methyl pyrrolidone & continued stirring until gets clear gel. The 30 gm of ornidazole was dissolved in gel with continueos stirring to get uniform mixture. The final volume was made up to 100ml mark with N- methyl pyrrolidone. Preparation example 2 to preparation example 5: We prepared the dental gel by the same method as described in the example 1 using different concentration of hydroxyl propyl methyl cellulose phthalate & various active drug substances. Table 1 shows their concentration. For example 1 the following studies were performed as a supporting data showing their efficacy and safety. In vitro release study: The in vitro release study was performed on the guinea pig & sheep oral mucosal membrane using artificial saliva as dissolution media. In vitro efficacy study for antibiotic and antibacterial/antifungal formulations: It is studied on the different strains of aerobic, anaerobic bacteria and fungi. In vivo release study: The study is performed on the affected patients of chronic periodontitis for 5 weeks. The saliva samples collected from affected area are analyzed for drug content In vivo safety & efficacy study: The study is performed on the affected patients of chronic periodontitis for 5 weeks. The swab samples from affected area collected & incubated on culture media & no of colonies observed are counted. Also, the decrease in the periodontal pocket size is measured with relation to time period. I Claim: - 1. A locally administrable, biodegradable & extended release delivery system for treatment of periodontitis comprising: Dental gel releasing therapeutically active substance for treating periodontitis which comprises: 1) Active substance in an amount of 10-40% w/v 2) Biodegradable polymer selected from the group consisting of phthalate derivatives having concentration in the range of 1025% w/v; 2. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1, where said active substance include antibiotics selected from group consisting of minocycline, tetracycline, oxytetracycline, tetracycline, amoxicillin, ampicillin, erythromycin, clarithromycin, azithromycin, bacitracin, kitasamycin, spiramycin & salts thereof or any other which can be used in periodontitis; 3. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include antibacterial /antifungal selected from group consisting of chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole & salts thereof or any other antibacterial/antifungal effective in periodontitis; 4. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include local anesthetic selected from group consisting of lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or salts thereof; 5. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include anti-inflammatory analgesics selected from group consisting of Aceclofenac, diclofenac, flubiprofen, ketoprofen, ibuprofen, mafenamic acid, aspirin, paracetamol, piroxicam & salts thereof or any other which help to reduce pain associated with periodontitis. 6. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include steroids selected from group consisting of hydrocortisone, dexamethasone, triamcinolone acetonide, & epihydrocortisone. 7. A process for the preparation of locally administrable, biodegradable, & extended release delivery system for periodontitis comprising steps of a. Making the biodegradable polymer gel in non aqueous solvent by dissolving polymer slowly with continuous stirring until clear gel is formed. The concentration of polymer is optimized between 10-25%w/v depending upon drug release required. b. Physiologically active drug entrapment in above prepared gel by adding it slowly with continuous stirring. The formation of gel ensured by faint clear gel characteristic odor & taste. The concentration of drug is optimized between 10-30% w/v depending upon category of drug used.

Full Text

FORM - 2
THE PATENTS ACT, 1970
(39 OF 1970 )
COMPLETE SPECIFICATION
(Section -10, rule 13)
"COMPOSITION FOR LOCAL DELIVERY OF MEDICINES FOR PERIODONTITIS & METHOD OF MAKING THE SAME"
Dr. Vishnu. K. Mourya, An Indian National Of Government College of pharmacy, Vedant road, Osmanpura, Aurangabad-431 005 (MH).
The following specification particularly describes the nature of the invention and the manner in which it is to
be performed.
The present invention relates with pharmaceutical composition for the treatment of periodontal diseases e.g. periodontitis. The composition to be applied directly into the periodontal pocket where it is supposed to give extended drug release for longer time.
In particular this invention relates to a process for making formulation for local delivery of active pharmaceutical substance for the treatment of periodontitis. Active may be selected from antibacterial, antibiotic, local anaesthetic or anti plaque and other as like with or without combination. Periodontitis (peri - around, odont = tooth, -itis = inflammation) refers to a number of inflammatory diseases affecting the periodontium- that is, the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by bacteria that adhere to and grow on the tooth's surfaces, along with an overly aggressive immune response against these bacteria. Most of the bacteria causing periodontitis includes anaerobic gram-negative bacteria in the subgingival area are Actinobaci-llusactinomycetemcomitans (Aa), Porphyromonas gingivalis, (Pg), Prevotella intermedia (Pi), and Tannerella forsythensis (Tf). These bacteria secrete colagenase that degrades periodontal ligament, connective tissue of the periodontal membrane. As a result periodontal membrane is separated and periodontal pocket is formed. Periodontitis can be diagnosed by inspecting the soft gum tissues around the teeth with a probe and radiographs by visual analysis, to determine the amount of bone loss around the teeth.
The removal of the periodontal plaque is the primary treatment for periodontitis. The plaque can be removed with the use of chemotherapy or by root planning and scaling called apparatotherapy. There are lots of problem associated with root planning and scaling e. g. instruments can't reach the area where bacteria used to stay, anatomical arrangement of the teeth restricts effective root planning & scaling. The only option remains is the chemotherapy.
The antibiotics like amoxicillin, doxycyclin, minocycline etc are effective in periodontitis.
The chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole etc can be used as antibacterial agents.
In addition to the bacterial infection, patients suffer with pain & inflammation of gingiva the present invention will be useful in all these conditions.
Local anaesthetics like lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or their salts help to reduce pain associated with periodontitis.
Improvement over known art:
The method by which a drug is delivered can have a significant effect on its efficacy. The most of the available therapies for periodontitis include systemic delivery of antibacterial or antibiotic. When administered systemically many drugs don't have an optimum concentration range within which maximum benefit is derived, thus delivery of these drugs can be toxic or produce no therapeutic benefit at all. On the other hand, the very slow progress in the efficacy of the treatment of periodontitis has suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to target in tissues. From this, new ideas on controlling the pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, biorecognition, and efficacy of drugs were generated. Thus, present work utilizes new strategies, often called drug delivery systems (DDS) based on interdisciplinary approaches that combine polymer science, pharmaceutics, bioconjugate chemistry, and molecular biology. Here we are aiming to minimize drug degradation and loss, prevention of harmful side- effects and to increase drug bioavailability arid the fraction of the drug accumulated in the required zone by focusing on local drug delivery and drug targeting systems having extended release effect.
The area defects or hardships in the prior art;
The well-known method in the treatment of periodontitis is effective removal of biofilm or periodontal plaque by means of scaling & root planning (RPS).
However despite biofilm removal patients still feel ongoing loss of attachments. One possible explanation for this clinical finding may be the inability of therapy to suppress periodontal pathogens to levels that are compatible with persistent periodontal health
Chemotherapy for periodontitis may be systemic or local. In systemic administration there is rapid declination in plasma drug concentration below therapeutic level. Thus, large dose of drug is required to maintain the drug concentration for its effective action. The large dose may lead to sideffects like hypersensitivity, gastrointestinal intolerance and drug interactions with alcohol and subsequent resistance to antibiotics. Thus during this therapy resistant bacterial strains may develop & normal bacterial flora may get eradicated. Thus local drug delivery may be a solution. But because of continues saliva flow, movement of tongue, lubricated oral soft tissues, and dislocating action from chewing food and drinking, locally administered drug may not able to achieve & maintain the required concentration at site to achieve therapeutic efficacy and limit side effects To overcome these problems there is need to develop technique to deliver drug at affected site with maintaining required concentration within therapeutic window for extended period- Actisite is the first subgingival DDS introduced both in the USA and Europe consists of fibers of ethylene vinyl acetate containing tetracycline. Actisite has extended release of tetracycline over a 10-day period. As it possesses lack of biodegradability it needs to be removed after treatment which diminishes its importance. Elyzol and dentomycin dental gels have most resorbable polymers like polycaprolactone, such as that used to degrade rapidly and most of the drug is released within 24 hr. The polycaprolactone is the biodegradable polymer releases 100% of the drug load within 24 hr, also its high cost to use it in potential applications renders it to least priority for use in dental gel thus it may not be used for extended release formulation. Another subgingival DDS exhists, which consists of a two part liquid system containing doxycycline hyelate as an active agent. Poly (lactide) is used as polymer with n- methyl pyrrolidone as a solvent. Here, poly (lactide) is having advantage as it gets precipitated as it comes in contact with water leading to extended release effect.
One formulation is developed using cellulose acetate hallow fiber in which drug is intrapped. As the formulation is in the form of fiber, it need to be cut in to the length for dosage & it need to coil around the teeth, then push into periodontal pocket for better effect. Thus it revealed that method is inconvenient to administer drug into periodontal pocket. According to EP A1 244118, PLGA microspheres with tetracycline are dispersed in Pluoronic gel & this formulation proposed to insert in periodontal pocket. The similar preparation also exists with minocycline. The formulations with these microspheres has disadvantage that as microspheres has hydrolytic property being made up from gel can not last for longer time period. Thus formulation is inconvenient for extended release therapy for periodontitis. From above description & literature sited for therapies for periodontitis, it is clear that no method is available which can deliver drug effectively at the site for extended period continuously having biodegradability with patient compliance in relation with dosing, cost and frequency of administration.
The present inventor took lots of trials for development of effective formulation for periodontitis aiming to have local administration, extended release effect with maintaining effective drug concentration continuously for eight days having patient convenience in relation to administration, dosing & cost.
By taking continuous trials for perfect formulation for periodontitis inventor came to conclusion that if the drug is entrapped in the gel prepared by using non aqueous solvent and biodegradable polymer which is supposed to get polymerized as soon as it get in contact with saliva. As the polymer is degraded slowly the polymerized matrix will release the drug continuously for extended period without interference of any external parameter.
Summary of invention: The present invention relates to locally administrable biodegradable and extended release pharmaceutical composition and process for preparation & filling thereof. The composition is to be administered directly in to periodontal pocket with the help of volume marked syringe.
The composition is in the form of non-aqueous gel made with biodegradable polymer having property to form polymer matrix as soon as it gets contact with water.
In addition present invention provides process for preparing a composition comprising the steps making the gel containing biologically active substance & filling the gel in syringes.
Detailed description of the invention:
The physiologically active substance which can be used for treating periodontitis contains antibiotics, antibacterials, local anaesthetics, antiinflammatory analgesics & steroids. Antibiotics which can be used in present invention may be minocycline, tetracycline, oxytetracycline, tetracycline, amoxicillin, ampicillin, erythromycin, clarithromycin, azithromycin, bacitracin, kitasamycin, spiramycin & salts thereof or any other which can be used in periodontitis.
The antibacterials or antifungals which can be used in present invention may be chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole & salts thereof or any other antibacterial/antifungal effective in periodontitis..
Local anaesthetics like lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or salts thereof & anti-inflammatory analgesics like diclifenac, flubipriofen, ketoprofen, ibuprofen, mafenamic acid, aspirin, paracetamol & salts thereof or any other which help to reduce pain associated with periodontitis.
The biodegradable polymer used in preparation of gel is phthalate derivatives like hydroxyl propyl methyl cellulose phthalate, cellulose acetate phthalate which can be absorbed into body. The concentration of polymer is having important effect on the drug release. Thus by optimizing concentration of polymer we can control the release time of drug.
The non aqueous solvent used for preparing gel is N - methyl pyrrolidone. It is having additional effect of drug permeation enhancer which will help to increase the applicability of formulation. The polymer 85 solvent used here is harmless to human body.
The gel is filled in syringe can be inserted directly into the periodontal pocket where on contact with water a polymer matrix is formed which lead to extended release of drug.
The following steps explains the process of making the gel
1) Dissolve the polymer in the N-methyl pyrrolidone to form the clear gel.
2) Step of making entrapment of drug in to gel.
3) Step of filling gel into volume marked syringe.
Step 1): The polymer hydroxyl propyl methyl cellulose phthalate is dispersed in N- methyl pyrrolidone with continuous stirring. The desirerable concentration of polymer used is between 10-to 25 % w/v. The concentration depends on the desired drug release required. The stirring continued until the clear gel is formed.
Step 2): The drug is ensured of having moisture less than 0.05%. The drug used is added slowly in formed gel with continuous stirring. The uniform mixing is ensured by observing clear gel having faint yellow color. The drug concentration is used in the range of 10- 40% w/v depending on type of action required e. g. antibacterial or analgesic.
The following examples can explain the applications of present invention. But the claims of the present invention are not limited within these examples.
The preparation example 1:
The preparation of the biodegradable dental gel using antifugals. The 16.7 gm of hydroxyl propyl methyl cellulose phthalate was dissolved in 70 ml of n-methyl pyrrolidone & continued stirring until gets clear gel. The 30 gm of ornidazole was dissolved in gel with continueos stirring to get uniform mixture. The final volume was made up to 100ml mark with N- methyl pyrrolidone.
Preparation example 2 to preparation example 5:
We prepared the dental gel by the same method as described in the example 1 using different concentration of hydroxyl propyl methyl cellulose phthalate & various active drug substances. Table 1 shows their concentration.

For example 1 the following studies were performed as a supporting data showing their efficacy and safety.
In vitro release study: The in vitro release study was performed on the guinea pig & sheep oral mucosal membrane using artificial saliva as dissolution media.
In vitro efficacy study for antibiotic and antibacterial/antifungal formulations: It is studied on the different strains of aerobic, anaerobic bacteria and fungi.
In vivo release study: The study is performed on the affected patients of chronic periodontitis for 5 weeks. The saliva samples collected from affected area are analyzed for drug content
In vivo safety & efficacy study: The study is performed on the affected patients of chronic periodontitis for 5 weeks. The swab samples from affected area collected & incubated on culture media & no of colonies observed are counted. Also, the decrease in the periodontal pocket size is measured with relation to time period.
I Claim: -
1. A locally administrable, biodegradable & extended release delivery system for treatment of periodontitis comprising:
Dental gel releasing therapeutically active substance for treating periodontitis which comprises:
1) Active substance in an amount of 10-40% w/v
2) Biodegradable polymer selected from the group consisting of phthalate derivatives having concentration in the range of 1025% w/v;
2. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1, where said active substance include antibiotics selected from group consisting of minocycline, tetracycline, oxytetracycline, tetracycline, amoxicillin, ampicillin, erythromycin, clarithromycin, azithromycin, bacitracin, kitasamycin, spiramycin & salts thereof or any other which can be used in periodontitis;
3. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include antibacterial /antifungal selected from group consisting of chlorhexidine gluconate, metronidazole, tinidazole, fluconazole, ornidazole & salts thereof or any other antibacterial/antifungal effective in periodontitis;
4. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include local anesthetic selected from group consisting of lidocaine, prilocaine, mepivacaine, articaine & bupivacaine or salts thereof;
5. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include anti-inflammatory analgesics selected from group consisting of Aceclofenac, diclofenac, flubiprofen, ketoprofen, ibuprofen, mafenamic acid, aspirin, paracetamol, piroxicam & salts thereof or any other which help to reduce pain associated with periodontitis.
6. The locally administrable, biodegradable and extended release delivery system as claimed in claim 1 where said active substance include steroids selected from group consisting of hydrocortisone, dexamethasone, triamcinolone acetonide, & epihydrocortisone.
7. A process for the preparation of locally administrable, biodegradable, & extended release delivery system for periodontitis comprising steps of
a. Making the biodegradable polymer gel in non aqueous solvent by dissolving polymer slowly with continuous stirring until clear gel is formed. The concentration of polymer is optimized between 10-25%w/v depending upon drug release required.
b. Physiologically active drug entrapment in above prepared gel by adding it slowly with continuous stirring. The formation of gel ensured by faint clear gel characteristic odor & taste. The concentration of drug is optimized between 10-30% w/v depending upon category of drug used.

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Patent Number

272334

Indian Patent Application Number

2536/MUM/2009

PG Journal Number

14/2016

Publication Date

01-Apr-2016

Grant Date

30-Mar-2016

Date of Filing

03-Nov-2009

Name of Patentee

VISHNU K. MOURYA

Applicant Address

GOVERNMENT COLLEGE OF PHARMACY, VEDANT ROAD, OSMANPURA, AURANGABAD-431 005, (MAHARASHTRA).

Inventors:

#	Inventor's Name	Inventor's Address
1	VISHNU K. MOURYA	GOVERNMENT COLLEGE OF PHARMACY, VEDANT ROAD, OSMANPURA, AURANGABAD-431 005, (MAHARASHTRA).

PCT International Classification Number

A61k31/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA