Linearity of Calibration Curves

Question: Describe about the Linearity of Calibration Curves? Answer: Construction of calibration curve The claibration stndards, 25, 50, 100, 150, 200 and 250 g/mL were used to construct the calibration curve. The results reveal that the high correlation coefficient (0.9996) value indicating the linearity1 of the curve across the concentrations employed (Table-1). Therefore the calibration parameters can be used for the calculation of drug concentrations from the samples collected during dissolution study. Table-1: Ansorbance and calibration parmeters Conc (mcg/mL) Mean Absorbance (n=3) 0 0 25 0.034 50 0.06 100 0.137 150 0.205 200 0.27 250 0.346 Correlation coefficient 0.99955 Slope 0.00139 Intercept -0.004 Data processing The absorbance values are subjected for determination of amount dissolved at timet using the equation-1. The concentrations o obtained are further multiplied by 1000, volume of dissolution media. The dissolution values at time t are corrected using the equation-2 and are shown in Table-2. Amount dissolved= (Absorbance-Intercept)/Slope-----------------1 Amount at time t= (Cn x 1000) + (Cn-1 x 10)--------------2 The data (Table-2) indicates that there exists a variation in the dissolution as it was evidenced from standard deviation values Table-2: Mean dissolutions of immediate and modified release tablets Time (Min) Immediate release Modified release Mean (mg) SD Mean (mg) SD 5 53.4 26.79 43.0 19.00 10 176.5 41.32 28.3 2.30 15 247.2 13.10 29.5 3.17 20 254.3 6.70 28.1 1.41 25 291.6 61.81 34.6 3.90 30 240.7 2.20 33.1 0.69 40 232.4 42.97 39.0 4.05 50 259.0 10.25 48.4 4.65 60 250.2 6.15 52.2 1.62 75 58.1 3.43 90 69.5 6.30 105 77.7 6.97 120 95.3 19.01 Fig-1: Comparison of dissolution profile of Ibuprofen from immediate and modified release Tablets The data so obtained is subjected for the modeling using the following equations3-6 Zero Order kinetics2,3 W0-Wt=K0t---------3 First order kinetics4 Log Wt = log W0 + K1t/2.303--------------------4 Higuchi model5,6 Wt=KHt1/2------------------5 HixsonCrowell model7,8 W01/3 Wt1/3 = Kst ------------6 Where W0 is the amount of drug present in pharmaceutical dosage9 or the initial amount of drug in solution (it is usually zero); Wt is the amount of drug released at time t; K0,K1, KH and Ks are release rate constants respectively in Zero order, First order, Higuchi and Hixson-Crowell models. The dissolution data was fitted into respective mathematical equation to calculate the correlation coefficient and release rate constants. The results are shown in Table-3. Table-3: Release kinetics of modified release tablets Kinetic model Correlation coefficient Release rate constant Mean SD Mean SD Zero Order 0.916 0.0670 0.828 0.047 First Order 0.848 0.1116 0.015 0.001 Higuchi square root law 0.732 0.1901 7.405 0.396 Hixon-Crowell cube root law 0.870 0.1009 0.004 0.000 Determination of time to release 70% and 90% drug release Based on the release kinetics, the modified release formulations appear to follow Zero order kinetics as it was evidenced from the correlation coefficients. The formulation showed high correlation coefficient indicates that formulations are following zero order release kinetics. Accordingly the equation-3 is modified in order to determine the time required to calculate the 70% and 90% drug. Wt=W0+K0t--------------------7 Since the drug release at time 0 is zero. Hence the equation can be rearranged to Wt=K0t t=Wt/K0 Accordingly the time required to release 70% (equal to 140 mg of the dose) and 90% (equal to 180 mg of dose) are calculated as follows t70 = 140/0.828 = 169.1 min t90 = 180/0.828 = 217.4 min Conclusions The calculations are performed and the dissolution profiles are compared. Modified release formulations are following zero order release kinetics. The time required to release 70% and 90% drug from modified release tablets respectively is 169.1 and 217.4 min References Joris, V., E, Marc., C, Christophe and B, Hedwig, Linearity of calibration curves: use and misuse of the correlation coefficient Accred Qual Assur Vol, 7, 2002, p. 281285 Varelas, CG., DG, Dixon, and C, Steiner, Zero-order release from biphasic polymer hydrogels Control. Release Vol, 34, 1995, p. 185192. 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