Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

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عابد, وفاء جاسم محمود
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An-Najah National University
Background: 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. However, no bioequivalence or stability studies are conducted for these extemporaneous preparations, which leads to confusion regarding its efficacy and safety. In silico and in vitro tools have proven to be useful in predicting the in vivo performance of drugs depending on its physicochemical properties and it’s in vitro dissolution profiles. No liquid formulation of combination Amlodipine and Valsartan is available in the pharmaceutical market for use in pediatric population with hypertension. Purpose: The aim of the present study was to prepare an extemporaneous suspension of Amlodipine and Valsartan from 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 Valzadepine®. The dissolution profiles for the extemporaneous preparation and the commercial tablet was 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 TM software was used to build absorption models for both drugs based on the in vitro dissolution data. The simulated plasma profile for both active ingredients were compared with the in vivo plasma profile 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 weeks period preserving its physical and chemical features. The release profiles of valsartan and Amlodepine from the suspension were similar to that from source tablet Valzadepine®. In silico modeling predicted similarity of the extemporaneous suspension and the commercial tablets. Conclusion: Amlodipine/Valsartan extemporaneous suspension could be prepared from available commercial tablets. Moreover, GastroPlusTM can be applied along with the in vitro dissolution in order to affirm similarity in extemporaneous compounding situations.