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Chitosan Based mostly Microparticulate Systems

CHITOSAN BASED MICROPARTICULATE SYSTEMS FOR THE DELIVERY OF LOCAL ANAESTHETIC

  1. Introduction :-

Chitosan structured micro particulate systems are used for the delivery of local anaesthetic drugs. Chitosan, which is abbreviated as (CS) is a polysaccharide. Chitosan is extracted from chitin, which is abundantly available in the skeleton of marine crustaceans. Chitin on deacetylation provides chitoson. Usage of chitin is limited because it's composition is similar to cellulose which is chemically inert. Chitosan and cellulose are experiencing similar structure i. e. both are made up of О (1-4) linked monosaccharide's, but the difference is chitosan is having 2-amino-2-deoxy-О-D-glucan combined with glycoside linkages. In chitosan framework the primary amine (- NH2 ) group is in charge of many pharmaceutical applications. Chitosan polysaccharide is having positive fee and it is mucoadhesive, this is the reason why chitosan can be used in many drug delivery applications. The molecular weight of chitosan is 3800 - 20, 000 Daltons. Chitosan is reactive in dynamics and it could be produced in various varieties like powder, paste, film, fibre etc. Chitosan is insoluble in normal water because of its cationic aspect in neutral or basic conditions, free proteins. Solubility of chitosan can be increased by addition of acid solution i. e. protonation of free amino acids will occur. Chitosan does not cause allergies and rejections hence it is recognized as bio compatible in dynamics. Chitosan breaks into amino sugar which amino body can absorb. Chitosan is non-toxic and it could be removed from the body without any aspect effects. Chitosan is having anti microbial property and it absorbs poisonous metals like Mercury, Cadmium, Lead etc. Chitosan is utilized for growing micro or nano- particle. The properties that makes its use are, release of active ingredients in a controlled manner, during the formulation no need of using organic solvents since it is soluble in acidic aqueous medium, free amino groupings are readily available for mix linking due to its cationic characteristics it allows ionic cross linking with multivalent anions, mucoadhesive character raises its residual time at the site of absorption.

Structure of chitin and chitosan

Structure of cross linked Chitosan

The complications engaged after surgery are high pain, reduced mobility, delayed recovery, long stay static in hospital. Really the only available system in professional medical practice is ON- Q pain buster, which is post operative treatment system. It provides ongoing infusion of local anaesthetic directly into the patient operative site for effective, non-narcotic post operative pain relief system for up to 5 days. You will find two pump models are available one with a set movement rate that individual cannot adapt and another with a fixed move rate that user can change.

ON-Q pain buster- post operative pain relief system

Advantages of ON-Q pain buster :-

  1. It is the better pain relief system than narcotics.
  2. It eliminates narcotic related area effects.
  3. It ensures convenient recovery, faster restoration and it reduces the space of stay in hospital.

Disadvantages of ON-Q pain buster :-

  1. Premature emptying of tank ball.
  2. In over doses medication toxicity will occur.

To defeat these side effects chitosan based medicine delivery systems are used. These particulate systems have got the properties like managed drug delivery, so that no poisonous effects will take place and these particulate systems are bio appropriate in character.

  1. Drug candidate :-

Local anaesthetic is a medicine which is employed for local anaesthetic result, that induces absence of pain feeling. Local anaesthetics having professional medical importance are divided into two classes, they may be, amino amide local anaesthetics which includes, Articaine, Bupivacaine, Cinchocaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Ropivacaine and Trimecaine. Amino ester local anaesthetic include, Benzocaine, Chlorprocaine, Cocaine, Cyclomethicaine, Dimethocaine, Piperocaine, Propoxycaine, Procaine, proparacaine, tetracaine. Among all the local anaesthetics Lidocaine is mostly used due to its short 50 percent life, faster onset of action, less adverse effects and low systemic toxicity.

Lidocaine :-

Structure :-

2- (diethyl amino) -N- (2, 6-dimethyl phenyl) acetamide

Preparation :-

The preparation of lidocaine will involve two steps,

Step 1 - 2, 6 - xylidene is cared for with chloracetyl chloride and then cured with

Chloracetyl chloride to give intermediate product.

Step 2 - intermediate product is cured with diethyl amine to provide Lidocaine.

Synthesis of Lidocaine

Mechanism of action :-

Lidocaine decreases the speed of depolarization by inhibiting sodium specific ion channels. Action potential won't arise anticipated to interruption of sodium ions influx and finally signal transmission will not occur.

Physico-chemical properties :-

Colour/ form - white or marginally yellow crystalline powder

Odour - quality odour

Boiling point - 180 - 1820C

Melting point - 68. 50C

Dissociation regular - 7. 86

Partition co-efficient - lidocaine is weakened base which is water

Insoluble, but it is soluble in its sodium form.

pH - local anaesthetic are weakened bases.

Pharmacokinetics :-

Onset of action - 45 to 90 moments.

Duration of action - 10 to 20 minutes.

Half life (t1/2) - 90 to 120 minutes.

Metabolism - Inside the liver organ 95 % of medicine goes through metabolism.

  1. Methods of preparation :-

Chitosan centered micro particulate system includes microspheres and nano-particles. These are spherical in shape and size ranges from 1m to 1000m diameter. There will vary kind of methods is there to prepare particulate systems, they can be,

  1. Emulsion cross linking :-

In this method aqueous chitosan solution is added to oil period which results in the forming of water in essential oil emulsion and ideal mix linking agent is added.

  1. Co-acervation/precipitation :-

By blowing chitosan droplets into alkali solution coacervate droplets are developed.

  1. Spray drying :-

In this technique atomized chitosan droplets are dried in a stream of heat and then ideal cross linking agent is added.

  1. Emulsion - droplet coalescence method :-

In this technique chitosan emulsion is added to NaoH emulsion. Up on high speed stirring chitosan droplets are created.

  1. Ionic gelation :-

In this method chitosan solution is added to polyanionic solution. Through to stirring chitosan droplets are produced.

  1. Reverse micellar method :-

In this technique chitosan solution and cross linking agencies are added to reverse micelle. By overnight stirring nanoparticles are shaped.

  1. Sieving method :-

In this technique, cross linking agent is put into chitosan gel. Up on sieving micro contaminants are made.

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