Electrospun fixed dose formulations of amlodipine besylate and valsartan

Abstract

Increasing numbers of elderly people require multi-drug therapies. One route to improve adherence rates is to prepare fixed dose combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. Here, we report the use of electrospinning to prepare fast-dissolving oral FDCs containing amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment of hypertension. Electrospun fibers were prepared loaded with one or both drugs, using polyvinylpyrrolidone as the polymer matrix. The fibers were largely cylindrical in morphology and comprise amorphous solid dispersions except with the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment efficiencies of >85% of the theoretical dose. The mats have folding endurances and thicknesses suitable for use as oral films. The amlodipine besylate-loaded systems are fast-dissolving, with >90% release obtained within 120 s. In contrast, valsartan release from its single-drug formulations took longer, ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360 s was achieved when the loading was 5% w/w of each drug, but again the release time increased with drug loading. Electrospun fibers therefore have significant promise as FDCs, but the target drug and its loading need to be carefully considered.

Fabrication and Characterization of Fast-Dissolving Films Containing Escitalopram/Quetiapine for the Treatment of Major Depressive Disorder

“…For the drug-loaded fibers, the lack of distinctive peaks of the drugs could be explained by the molecular dispersion of these drugs within the fibers that were transformed by the electrospinning process. This expected observation is consistent with [ 33 , 35 , 44 , 47 ]. Overall, this XRD finding further confirmed the results of the DSC, which suggest that the drug-loaded coaxial fibers were in the amorphous solid dispersion form.…”

“…Pure PVP showed a broad endotherm between 44.7 and 115.9 °C, which indicates water evaporation, owing to the hygroscopic nature of this polymer [ 32 ]. The polymer is also known to be amorphous; therefore, it is expected to show no sharp melting endotherms [ 47 ]. In the PM thermogram, the drug’s characteristic endothermic peaks that represent their melting points were merged, broadened, and shifted toward lower temperatures (142.4 and 166 °C for ESC and QUE, respectively), and their intensity was reduced.…”

“…XRD was used to investigate the physical state of the drugs after electrospinning, as it was previously reported that this technique can lead to the formation of amorphous solid dispersion [ 35 , 44 , 47 ]. The results in Figure 4 illustrate that the pure ESC and QUE drugs were in crystalline form, which was identified by the presence of multiple distinct sharp peaks (Bragg reflections) in their corresponding XRD patterns.…”

Electrospun fibers and their application in drug controlled release, biological dressings, tissue repair, and enzyme immobilization

“…Electrospun nanobers have a large specic surface area and porosity, and some electrospun ber materials have good biocompatibility and degradability, which can be used as drug carriers. Electrospun nanobers have good application prospects in tissue repair, 1,2 biological dressing, 3,4 drug controlled release [5][6][7] and enzyme immobilization. Tissue repair is the main research direction in the eld of biomedical applications, and electrospun ber materials were rst applied to vascular repair tissue engineering in 1978.…”

Fabrication of Electrospun Levodopa-Carbidopa Fixed-Dose Combinations

“…Electrospun fibers have been widely explored to generate drug delivery systems, and there are reports in the literature of fast-dissolving [17][18][19][20], extended release [21][22][23], and pH responsive systems [24,25], among many others. Fixed-dose combination formulations have also been prepared by electrospinning [26,27], but there are few studies where multiple drugs have been combined into a single fiber formulation.…”