Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

Abstract

Background and Objectives. In case of absent liquid dosage form, crushing a tablet or dispersing a capsule would be the most convenient option for using these drugs in patients with dysphagia difficulties. The aims of the study were to prepare an extemporaneous suspension of amlodipine and valsartan from the available commercial tablets and to evaluate the stability and dissolution properties of the compounded suspension. Method. Amlodipine/valsartan extemporaneous suspension was prepared from available commercial tablets such as Valzadepine®. The dissolution profiles for the extemporaneous preparation and the commercial tablet were determined in different pH media. The physical, chemical, and microbial stability of the compounded formulation was evaluated over one-month period at room temperature. Moreover, in silico modeling using GastroPlus™ software was used to build absorption models for both drugs based on the in vitro dissolution data. The simulated plasma profiles for both active ingredients were compared with the in vivo plasma profiles to examine the similarity of the extemporaneous suspension and the commercial tablets. Results. The amlodipine/valsartan extemporaneous suspension was successfully prepared with acceptable organoleptic properties. The suspension was stable for four-week period preserving its physical and chemical features. The release profiles of valsartan and amlodipine from the suspension were similar to those from source tablet Valzadepine®. In silico modeling predicted the similarity of the extemporaneous suspension and the commercial tablets. Conclusion. Amlodipine/valsartan extemporaneous suspension could be prepared from available commercial tablets. Moreover, GastroPlus™ can be applied along with the in vitro dissolution in order to affirm similarity in extemporaneous compounding situations.

Fractional modeling of drug diffusion from cylindrical tablets based on Fickian and relaxed approaches with in vivo validation

“…Moreover, the improved results can be seen in the external medium with upgrading the fractional order of the TFM in the case of 4‐WSGD. Figure 8 demonstrates and compares these results with the plasma data 70 . It is evident from the graph that, with better precision, there is a rapid decline in the drug mass.…”

“…The drug release physical problem from a multi‐layer cylindrical tablet is dependent on a wide range of parameters. To simplify this article, Table 1 summarizes the used parameters that were taken from the literature 70 . The release distances and were estimated to generate a totally tablet drug depletion and a fully release and absorption time of about 140 h for Amlodipine and 70 h for Valsartan.…”

“…Mass develops gradually across an enlarged distance at a time in the dissolution medium, depending on the diffusive features of the tablet. The simulated mass profiles for both drug materials were compared with the in vivo in Aabed et al 70 …”

“…To simplify this article, Table 1 summarizes the used parameters that were taken from the literature. 70 The release distances R s ≈ 18R 0 and Z s ≈ 4Z 0 were estimated to generate a totally tablet drug depletion and a fully release and absorption time of about 140 h for Amlodipine and 70 h for Valsartan. All computations were performed using MATLAB R2022b software.…”

“…Mass develops gradually across an enlarged distance R s at a time in the dissolution medium, depending on the diffusive features of the tablet. The simulated mass profiles for both drug materials were compared with the in vivo in Aabed et al 70 The TFM is presented to consider the finite propagation speed and overcome the infinite one of the CFM by utilizing the FD's memory effect. Figure 6 shows that the NC profiles along the normalized distance with different fractional order α ¼ 0:88,0:85, and 0:80 for the TFM based on 4-WSGD approximation.…”