DRUG RELEASE Assignment-MAH_130115_25370_3_49567

Construction of calibration curve

The claibration stndards, 25, 50, 100, 150, 200 and 250 µg/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

Data processing

The absorbance values are subjected for determination of amount dissolved at time‘t’ 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

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 kinetics^2,3

W₀-W_t=K₀t———3

First order kinetics⁴

Log W_t = log W₀ + K₁t/2.303——————–4

Higuchi model^5,6

Wt=K_Ht^1/2——————5

Hixson–Crowell model^7,8

W₀^1/3 –W_t^1/3 = K_st ————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, K_H 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

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.

W_t=W₀+K₀t——————–7

Since the drug release at time ‘0’ is zero. Hence the equation can be rearranged to

W_t=K₀t

t=W_t/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

1. 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. 281–285
2. Varelas, CG., DG, Dixon, and C, Steiner, ‘Zero-order release from  biphasic polymer hydrogels’ J. Control. Release Vol, 34, 1995, p. 185–192.
3. Suvakanta,  D.,  PN, Murthy., L, Nath and P, Chowdhury, ‘Kinetic modeling on drug release from controlled drug delivery systems’ Acta Poloniae Pharmaceutica Drug Research, Vol. 67, 2010, no. 3, p. 217-223
4. Mulye, NV and SJ, Turco, SJ, ‘A simple model based on first order kinetics to explain release of highly water soluble drugs from porous dicalcium phosphate dihydrate matrices’, Drug Dev. Ind. Pharm. Vol. 21, 1995, p. 943–953
5. Desai, SJ., P, Singh., AP, Simonelli and WI, Higuchi, ‘Investigation of factors influencing release of solid drug dispersed in inert matrices. IV. Some studies involving the polyvinyl chloride matrix’ J. Pharm. Sci. Vol, 55, 1966, p. 1235–1239.
6. Higuchi, WI, ‘Analysis of data on the medicament release from ointments’. J. Pharm. Sci. Vol, 51, 1962, p. 802–804.
7. Hixson, AW and JH, Crowell, ‘Dependence of reaction velocity upon surface and agitation’ Ind. Eng. Chem. Vol, 23, 1931, p. 923–931.
8. Niebergall, PJ., G, Milosovich and JE, Goyan, ‘Dissolution rate studies. II. Dissolution of particles under conditions of rapid agitation’ J. Pharm. Sci. Vol, 52, 1963, p. 236–241.
9. Costa, P and JM, Sousa., ‘Modeling and comparison of dissolution profiles’ Eur J Pharm Sci. Vol. 13, 2001, no. 2, p. 123-33.