Rate constants solid dosage forms

The most common extravascular route is oral. When a solution or a rapidly dissolving solid dosage form is given orally, the absorption process often obeys first-order kinetics. In these cases, absorption can be characterized by evaluating the absorption rate constant, ka, using plasma concentration versus time data. 

When several temperature-dependent rate constants have been determined or at least estimated, the adherence of the decay in the system to Arrhenius behavior can be easily determined. If a plot of these rate constants vs. reciprocal temperature (1/7) produces a linear correlation, the system is adhering to the well-studied Arrhenius kinetic model and some prediction of the rate of decay at any temperature can be made. As detailed in Figure 17, Carstensen s adaptation of data, originally described by Tardif (99), demonstrates the pseudo-first-order decay behavior of the decomposition of ascorbic acid in solid dosage forms at temperatures of 50° C, 60°C, and 70°C (100). Further analysis of the data confirmed that the system adhered closely to Arrhenius behavior as the plot of the rate constants with respect to reciprocal temperature (1/7) showed linearity (Fig. 18). Carsten-sen suggests that it is not always necessary to determine the mechanism of decay if some relevant property of the degradation can be explained as a function of time, and therefore logically quantified and rationally predicted. 

The degradation of a colorant in a solid dosage form was found to follow a zero-order reaction with a rate constant of 3.1 x lfh4 absorbance units per hour at 37°C. What is the half-life of the preparation with an initial absorbance of 0.56 at 486 nm This dosage form should be discarded when the absorbance is below 0.34. Calculate the predicted life of the dosage form at 37°C. 

The stability of solid dosage forms is usually very susceptible to the moisture content of the atmosphere in the container in which they are stored (see section 4.4.3) A linear relationship between log k and the water vapour pressure for vitamin A palmitate beadlets in sugar-coated tablets has been found. Similarly, a linear relationship between the logarithm of the rate constant for the decomposition of nitrazepam in the solid state and the relative humidity has been established (Fig. 4.f9). The need for consideration of the effect of moisture on stability has been stressed by Carstensen, who stated that stability programmes should always include samples that have been artificially stressed by addition of moisture. One purpose of a stability programme should be to define the stability of the dosage form as a function of moisture content. 

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