PREPARATION AND EVALUATION OF SUSTAINEDRELEASE MICROPARTICLES OF NORFLOXACIN Prepared & Presented by : - RAJA CHAKRAVERTY M Pharm
INTRODUCTION Oral controlled drug delivery systems represent the most popular form of sustained drug delivery systems for the obvious advantages of oral route of drug administration. Such systems release the drug with constant or variable release rates . Attempts to maintain a steady level of medication using biodegradable polymers have recently attracted considerable attention. Because, these polymers are biodegradable, they do not require retrieval after the medication is exhausted. Therefore, they can be fabricated into microspheres, microcapsules or nanospheres, with the drug encapsulated in them. Various microencapsulation techniques for incorporating a bioactive agent into a microparticle carrier are there . Some of the advantages of using microparticles as sustained release drug delivery systems are an effective protection of the active agent against degradation ( e.g. : enzymatic) after encapsulation(1). The possibility to accurately control the release rate of the incorporated drug over periods of hours to months an easy administration
INTRODUCTION The principle of gelation is based on the formation of tight junction between the glucoronic acid residues of sodium alginate. Number of apparent cross-linking points formed within the Calcium alginate gel beads increase with increased alginate concentration. The increase in the apparent cross-linking density delays the alginate gel disintegration in phosphate buffer due to retardation of calcium-ion (Ca++) exchange with sodium (Na+) and eventually leads to the increase of lag time. Ionotropic gelation is based on electrostatic interaction between amine groups of polymer and negatively charged group of polyanion. Chemical reaction between sodium alginate and calcium chloride is utilized in micropellet formation. The gelation of alginate is caused by formation of an egg box junction to associate divalent metal ions of alginate polymer chain. Sodium alginate has been used as matrix material to achieve a control release drug delivery due to its hydrogel formation properties. Gelation of an anionic polysaaaccharide, sodium alginate, was achieved with oppositely charged counter ions i.e. Ca ++ to form microparticles which are further sustained using a divalent polymer.
OBJECTIVE The objective of this undertaken project is the preparation and evaluation of sustained release microspheres of norfloxacin. NORFLOXACIN
PREPARATION OF MICROSPHERESBY IONOTROPIC GELATIONTECHNIQUE PROCEDURE : STEPS INVOLVED IN THE GENERAL PREPARATION OF MICROPARTICLES BY IONOTROPIC GELATION TECHNIQUE :- 1. First of all, weighed accurately all materials required for the experiment including the drug used (Norfloxacin), sodium alginate and calcium chloride. 2. Distilled water is then added to the weighed quantity of sodium alginate to make aqueous mucilage of it in a beaker and allowed to heat for 5-10 minutes in a hot plate. 3. Following it, Distilled water is also added to the weighed quantity of calcium chloride to make a solution in it. 4. The aqueous mucilage of sodium alginate is then stirred in a magnetic stirrer at a suitable speed (rpm) for 30 minutes. 5. The Drug (Here: Norfloxacin) is dispersed in the aqueous mucilage of sodium alginate subsequently and stirred at suitable speed in the magnetic stirrer. 6. The microparticles are formed by dropping the bubble free dispersions through a glass syringe with the help of a needle (size-16/18) into the gently agitated calcium chloride solution in 100ml. 7. ‘Cured’ the microparticles for 30 mins. and then filtered & washed thoroughly with distilled water. 8. The pellets were then oven dried for 2-4 hrs at about 50 degree centigrade. 9. Dried at room temperature subsequently for few hours and used subsequently.
STANDARD CURVE OF NORFLOXACIN STANDARD CURVE OF NORFLOXACIN IN PHOSPHATE BUFFER PH 6.8 STANDARD CURVE IN 0.1 (N) HCL PH (1.2) 1.2 0.7 0.6 1 y = 0.1677x y = 0.0971x 0.5 0.8ABSORBENCE 0.4 ABSORBENCE Series1 Series1 0.6 Linear (Series1) Linear (Series1) 0.3 0.4 0.2 0.2 0.1 0 0 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 CONCENTRATION (mcg/ml) CONCENTRATION (mcg/ml) PHOSPHATE BUFFER PH 6.8 HCL BUFFER PH 1.2
DRUG ENTRAPMENT EFFICIENCY PROCEDURE : Accurately weighed microparticles equivalent to 20 mg and suspended in 250 ml of simulated intestinal fluid pH=6.8 and kept for 24 hours. Next day, stirred for 5 minutes and filtered. After suitable dissolution, drug content was analyzed spectrophotometrically at 278 nm. Then Drug Entrapment Efficiency (%) was determined through formula. Drug Entrapment Efficiency = (Actual Drug content / Theoretical Drug Content) x 100% DRUG ENTRAPMENT EFFICIENCY (A1) = 42. 22 % DRUG ENTRAPMENT EFFICIENCY (A2)= 54.84 % DRUG ENTRAPMENT EFFICIENCY (A3)= 37.52 %
RESULT & DISCUSSION Chemical reaction between sodium alginate and calcium chloride to form calcium alginate was utilized for microspheres. A1 & A2 exhibited similar swelling profiles whereas A3 show greater swelling compared to other two formulations. A2 formulation showed best sustained release amongst the three formulations releasing about 40.51 % in 5 hrs .Formulation A3 showed greatest percent swelling over time. The Drug Entrapment Efficiency, a crucial parameter in such formulations is given below :- A. Drug entrapment efficiency (A1) = 42. 22 % B. Drug entrapment efficiency (A2) = 54.84 % C. Drug entrapment efficiency (A3)= 37.52 %
CONCLUSION Sustained release microparticles were successfully prepared employing ionotropic gelation technique where the natural water soluble polymer, namely, sodium alginate prolongs the release of the drug. The method of preparation was found to be simple and without the use of organic solvents. Micropellets prepared are spherical in shape and having a porous surface. The Drug Entrapment Efficiency of formulation A2 prepared with 2%w/v calcium chloride showed the best result of around 55 % DEE. This could have been further improved upon by the use of co-polymers. The micropellets were found to be effective in sustaining the drug release with the formulation A2 releasing around 40.51 % drug in 5 hours. Drug release is diffusion controlled and follows first order kinetics. The process of drug release from the polymer-dry matrix is through gelation of the polymer. Swelling studies showed A3 getting swelled up fastest while A2 exhibited least swelling and this fact is corroborated with the faster dissolution of formulation A3 and the sustained release effect shown by A2 in the In-vitro Dissolution study.