DDSolver Software Application for Quantitative Analysis of In vitro Drug Release Behavior of the Gastroretentive Floating Tablets Combined with Radiological Study in Rabbits

Abstract

Background: Gastroretentive drug delivery systems (GRDDSs) are designed to release the drug in the stomach over a prolonged time; thus, they can reduce drug dosing frequency and dose size and improve patient compliance. GRDDSs are also highly effective in enhancing the bioavailability of the drug that exhibits window absorption in specific segments of the gastrointestinal (GI) tract. Famotidine (FMT), an H2 receptor antagonist, is an example of these drugs. FMT is a slightly water-soluble drug but well soluble in an acidic medium. This research aims to formulate FMT gastro-retentive floating tablets (FMT-GRFTs) to improve the bioavailability and therapeutic activity of the drug and increase patients' adherence to treatment. In addition, the in vitro release behavior of the prepared FMT-GRFTs was quantitatively analyzed using the DDSolver software to assist in selecting the successful formulation that was then evaluated in vivo. Methods: The direct compression technique prepared numerous tablet formulations and was subjected to the pre-and post-compression evaluation. Data of FMT dissolution in the simulated gastric medium was analyzed by various kinetic models built in the DDSolver program. In addition, the simulated pharmacokinetics (AUC, MDT, and MRT), R2 adjusted, AIC, MSC, correlation of the residuals, and similarity factor (f2) were also generated. Results: The results revealed that FMT release from the candidate formula (FH3) fitted to the first-order kinetic model, with a high value of R2 adjusted and MSC and a low AIC. The release behavior exhibited the Fickian diffusion mechanism. The similarity factor showed no significant difference (p < 0.05) of the test sample compared to the reference product. Nevertheless, the simulated pharmacokinetic parameter, AUC, proved a two-fold enhancement in FMT bioavailability, with a significant increment in the MDT and MRT compared with the reference product. The FT-IR spectroscopy analysis indicated the absence of drug-excipients/polymer interaction. The in vivo X-ray studies on rabbits confirmed that the floating tablets showed nearly eight hours of gastric residence. Conclusion: DDSolver software was helpful in deciding the optimized formulation of FMT floating tablets. The radiological examination in rabbits for gastric retention was consistent with the release data analysis in vitro.

Pomegranate extract-loaded sphingosomes for the treatment of cancer: Phytochemical investigations, formulation, and antitumor activity evaluation

“…According to the shape parameter (β) of this model, the release of the phenolic compounds was following Fickian diffusion, since the β value was ≤0.75 for all three formulations [ 41 ]. This was confirmed by the Korsmeyer-Peppas model, where the n value for F1, F2, and F3 was < 0.45, indicating the phenolic compounds released by Fickian diffusion as well [ 42 ]. One of the elements affecting the drug’s diffusion, according to Fick’s first law, is its dose or initial concentration, therefore, a rise in EE% corresponds to a higher initial concentration of the PE loaded into sphingosomes.…”

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

“…The height and the diameter of the formed cone were measured after all of the powder in the funnel was evacuated. The angle of repose was calculated using Eq 2 [ 19 ]: …”

“…The obtained measurements were compared to a standard reference to judge the flow properties of powder. As shown in Eqs 5 and 6 [ 19 ]: …”

Development of Clindamycin Loaded Oral Microsponges (Clindasponges) for Antimicrobial Enhancement: <i>In Vitro</i> Characterization and Simulated <i>in Vivo</i> Studies

“…The R 2 of all the models was compared to find the best model that best fitted the drug release data. Then, the % of fraction dissolved for both the observed data and the predicted data were computed, compared, and presented as line charts by the use of DDSolver Excel add-in software [21].…”