TO DETERMINE THE SHELF LIFE OF IBUPROFEN SOLUTION

Transcription

1 TO DETERMINE THE SHELF LIFE OF IBUPROFEN SOLUTION AIM: To etermine the shelf life of solution using accelerate stability stuies. MATERIAL REQUIREMENT, ethanol, phenolphthalein, soium hyroxie (0.1N), glass wares, ryer etc THEORY Most of the rugs purchase from the retail shop contain expiration ate on the label of pack. The expiration ate is an assurance given by the manufacture that, if the prouct is taken before the expiry of the labele ate, the osage form fulfils the specifications presente on the label regaring ientity, strength, quality, an purity. The Drug Control Department ensures through regulatory controls, that every prouct release into the market shoul be evaluate to fix the expiry ate. The technical term for expiry time is shelf life. 1 By convention, shelf life is efine as the time require for a rug to reuce its concentration to 90% of the labele concentration. The evaluation of shelf life is essential because the stability of a rug in osage forms can be influence by the normal environment conitions. Drugs, such as esters (for example aspirin, procaine) an amies (for example chloramphenicol), unergo hyrolytic reactions uring storage uner normal conitions. Similarly rug such as ascorbic aci, promethazine unergo oxiation reaction. As a result, the rug may not exhibit the esire effect an may show reuce biological response. Since egraation or ecomposition involves chemical alteration (reaction) of the active ingreient, the knowlege of chemical kinetics is helpful to preict the reaction rates an further to evaluate the shelf life. Stability consieration also inclues change in physical appearance of the proucts. In oler metho, a prouct is place at room temperature or in refrigerator in orer to mimic the shelf conitions an the stability is evaluate for a prolonge perio of 2to 5 years. Such a esign of experimentation is time consuming an uneconomical. The reaction rate is accelerate by carrying out the reaction at elevate temperature. Therefore, by conucting the experiment, a factor is obtaine that has a linear relationship with temperature. The analytical metho is such that either starting material or ecompose prouct alone can be analyze, while other compoun ies not interfere with the metho of estimation. Therefore, a stability inicating assay proceure is essential for conucting the stability stuies. 1, 2 The results of accelerate ecomposition are extrapolate to the room temperature, i.e., 25 o C or specific refrigerator conitions. We generally assume that the rug reaction is zero orer or first orer. Accelerate stability stuies are an experimental esign to evaluate the stability of a prouct by accelerating the rate of reaction. A more comprehensive pharmacopoeial protocol (USP) involves the evaluation of 1. Chemical integrity, 2. Physical changes. Test for sterility, resistance to microbial growth, toxicity an bioavailability stuies are carrie out, wherever necessary. Such stuies enable the preiction of shelf life for each influence of temperature on egraation. In general, the rate or a reaction increases with

2 the rise in temperature. Arrhenius establishes a more quantitative relationship between temperature an rate of reaction. The exponential equation is: K= Ae -Ea/RT Where K=specific rate constant A= frequency factor or Arrhenius factor Ea=energy of activation, KJ/mol.K T= absolute temperature Arrhenius factor or frequency factor is a measure of the frequency of collision that can be expecte between the reacting molecules in reaction. Energy of activation is efine as the minimum energy require by the molecule so the molecule so the molecule so the molecular collisions give useful proucts. logk=log A- Ea/2.3.3RT Accoring to this equation, a plot can be rawn by taking logk on ay axis an reciprocal temperature (1/T) on x axis. The slope gives the energy of activation. Ea=slope *2.303*R Where R=8.314 J/mol.K 1, 2, 3 follows pseuo-first orer kinetics PROCEDURE 1) Stanar curve preparation I. A weight of accurately 100 mg of was taken & issolve in 100 ml of 0.1 N NaOH solution.( solution A ) II. From the solution A 10 ml was pipette out & ilute to 100 ml in a volumetric flask with 0.1 N NaOH solution ( solution B ) III. From solution B ifferent volumes of 0.1 ml, 0.2 ml, 0.4 ml, 0.6 ml 0.8 ml & 1ml were taken an ilute up to 10 ml with0.1 N NaOH solution. IV. The absorbance was measure at 223 nm in U V spectrophotometer against 0.1 N NaOH solution as blank. 4 V. A graph was plotte by taking concentration VS absorbance. 2) Accelerate stability stuies 3 About 100mg of was accurately weighe an transferre the into a 250 ml conical flask. About 1 or 2 ml alcohol was ae to issolve the an makeup 100ml with0.1 N NaOH solution. The conical flask was corke an kept in water bath at 40 o C Immeiately after placing in water bath, 1ml sample of mixture was taken which represents zero time samples. At regular interval of 10, 20,30,40,50 an 60minutes,1 ml of samples were withrawn from the container an makeup the volume to 10 ml with 0.1 N NaOH solution

3 The absorbance was measure at 223 nm in U V spectrophotometer against a blank. A graph was plotte by taking time on x axis an log percent aspirin unecompose on y axis. The same proceure was repeate at 60 o c an 70 o c The slopes of these graph were calculate an, Arrhenius plots were mae by plotting logarithm of rate constants against the reciprocal of absolute temperature. 3) ASSAY PROCEDURE 4 Accurately 0.4 gm was weighe an issolve in 100ml of ethanol (95%). This solution was titrate with 0.1n NaOH using 0.2 ml phenopthalein. Performe a blank etermination make any correction. Each ml 0.1N NaOH is equivalent to gm of. EVALUATION TABLE 1 Stanar curve of CONCENTRATION (µg/ml) ABSORBANCE TABLE 2: ecomposition store at 50 o C Measure absorbanc conc. e (µg/ml) Tim e (min ) ecompose, % unecompos e unecompos e

4 TABLE 3: ecomposition store at 60 o C Time I (min) conc. µg/ml Absorba -nce ecompose % - x100 unecompose TABLE 4 ecomposition store at 70 o C Time (min) absorbance conc. µg/ml ecompose, % x100 unecomp ose

5 y = 0.044x R 2 = Fig-1 stanar curve of Figure-2 ecomposition profile store at50 o C, 60 o C an 70 o C