Modeling and Comparison of Dissolution Profiles of Diltiazem Modified-Release Formulations

Abstract

Generic drugs offer a cost-effective alternative to brand-name products. However, the main concern with modified-release formulations is the substitution of one product for another. Accordingly, the first objective of this study was to assess the interchangeability of the available diltiazem extended-release (ER) products on the basis of their in vitro dissolution characteristics using USP Apparatus 2 and 3. The second objective was to compare dissolution profiles in simulated fasted and fed states and determine whether there is a change in the mechanism of drug release. Dissolution profiles characterized using Apparatus 2 or 3 under fasted conditions were similar. However, Apparatus 3 testing provided a more discriminating and comprehensive evaluation of the drug release performance of ER products. Testing using Apparatus 3 in the fed state highlighted some difference in dissolution profiles, suggesting a food effect on drug release. This implies that, depending on the targeted concentration, a patient should be instructed whether to take the medication in fasted or fed state. The study therefore shows the necessity of testing the products in both fasted and fed states to determine their similarity and therapeutic interchangeability. Apparatus 3 testing was also more accurate in determining the release mechanism than the Apparatus 2 method. No change in the mechanism of drug release between fasted and fed state was observed.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

“…44 DE is another parameter used to express dissolution profile between different formulae; it is the area under the diffusion curve up to certain time, t, expressed as a percentage of the area of the rectangle described by 100% diffusion in the same time. 45 DNS-F7 and CS-DNS-F10 showed 1.6-and 1.2-fold increase in DE than that in DCN dispersion, respectively, which ensure the enhancement of the dissolution efficiency of DCN-NS and CS-DCN-NS over crude DCN powder due to size reduction.…”

Preparation and in Vitro Evaluation of Fast Release Diazepam Suppositories for Febrile Seizures

“…In all formulas, n is bigger than 0.45 and smaller than 0.89, this indicates a non-Fickian diffusion [18]. Therefore, the release has occurred probably by diffusion, swelling and erosion.…”

“…8, and the most important functional groups are mentioned in Table 4. The bands 1680, 1605, 1400, 1320, 740, 700, and 580 cm −1 appear to be characteristic of the 1, 4-benzodiazepine structure [18][19][20]. C=O stretch, a very strong infrared absorption band was observed about 1680 cm −1 in the spectra of diazepam [22].…”

Physicochemical and dissolution profile characterization of pellets containing different binders obtained by the extrusion-spheronization process

“…Under these conditions, the challenge to overcome is considerable: to formulate a product capable of retaining the drug at a pH of close to 7.0 and then, soon after, to promote its rapid delivery in an acidic pH environment. It is exactly in this type of situation that Bio-Dis comes into its own, because it was designed specifically for tests in which a change in the pH of the medium is a reality (Yu, Wang, Hussain, 2002;Pezzini, Ferraz, 2009;Samaha, Shehayeb, Kyriacos, 2009). Thus, the use of a pH close to neutral for evaluating the initial minutes of dissolution, combined with a very low stirring speed (only 4 OPM) for a short period of time (5 minutes), followed by transposition to a acidic pH value with a higher stirring speed (10 OPM), is the precise basis for the aforementioned conditions.…”