The paper presents a method for the calculation of fractal reaction dimension, D-R, in dissolution studies of powdered substances with a given particle size distribution. An estimate for D-R can be directly obtained from dissolution experiments using the well known Hixson-Crowell equations in a modified form. The estimation is accomplished with a special computer program in BASIC which was developed and applied to simulated errorless and contaminated data with very good results. A practical demonstration of the method's usefulness was shown on experimental data taken from the literature.

A model based on the fractal methodology is proposed for the kinetic study of carrier-mediated transport under heterogeneous conditions, i.e., when the drug-carrier interaction occurs at an interface with an effective dimensionality smaller than the embedding dimension of d = 2. A model equation is derived for the flux, based on a similar approach for an analogous equation for enzyme kinetics. It is shown that the total flux-solute concentration plots are curvilinear when the fractal dimension is smaller than unity while they become biexponential, with ascending and descending limbs, when the fractal dimension D is in the range 1 < D < 2. Nonlinear Lineweaver-Burk plots are obtained when this fractal kinetics approach is used. Good fittings are obtained when the fractal model is applied to literature data previously analysed with a combined transport mechanism, revealing experimental systems that display a D value in the range 1 < D < 2. It is suggested that transport studies should be carried out at a wider working solute concentration range and various agitation and incubation conditions in order to derive definite conclusions for the transport pathways.

Bioequivalence assessment of extended release (ER) dosage forms is usually carried out at steady-state, using area under the curve (AUG) to evaluate extent of absorption and maximum concentration (C-max) and % peak trough fluctuation ratio (%PTF) to evaluate rate of absorption. Other metrics such as C-max/AUC and partial AUCs have recently been proposed as alternatives for assessing the absorption rate of drugs from immediate release (IR) dosage forms under single dose conditions. The performances of these metrics were assessed using the results of two sets of simulated experiments of ER dosage forms at steady-state and 2 actual pharmacokinetic studies involving ER dosage forms of a Glaxo drug. In the first set of simulations there was no difference in bioavailability between the two formulations; in the second set of simulations the test formulation had a 50% greater absorption rate-constant (ka) than the reference formulation. The following conclusions were reached: 1. For ER dosage forms at steady-state, all the metrics, with the exception of %PTF, resulted in much smaller increases than the underlying 50% increase in ka. Although, %PTF gave the largest effect it was also the most imprecisely estimated. 2. In our studies, none of the metrics tested provided reliable information about changes in the underlying rate of absorption from ER dosage forms under steady-state conditions. 3. The current practice of comparing rate of absorption from ER dosage forms using steady-state C-max is inappropriate due to lack of sensitivity. The use of %PTF may require a widening in the currently accepted 80-125% permissible range set for C-max and AUC.

A diflunisal ion selective electrode of the PVC membrane type with an ion-exchanger consisting of the tetraheptylammonium-diflunisal ion pair is described. The sensor exhibits a rapid, near-Nernstian, selective response to diflunisal anion in the pH range 7-10, with a (batch) detection limit of 1 x 10(-5) M. The ion sensor was used as a flow detector in an automated flow-injection analyzer to develop routine methods for assays (concentration range 1-50 x 10(-4) M, (flow) detection limit 2.6 x 10(-5) M), content uniformity, and dissolution studies of diflunisal formulations. No serious interference from common ions and tablet excipients was found, and the drug can be directly determined in colored samples without separation steps. Fourty measurements can be performed automatically per hour with a precision of 0.5-1.8% relative standard deviation. The automated method for the dissolution test provides a complete dissolution profile by the end of the experiment. Using the constructed ion sensor, the intramolecular hydrogen bonding of the diflunisal anion was studied, thereby revealing a new application of ion sensor potentiometry.