Fast-Dissolving Nifedipine and Atorvastatin Calcium Electrospun Nanofibers as a Potential Buccal Delivery System

Abstract

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients' convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e., tablets and capsules. These nanofibers prepared either as single- or multi-layered fibers could hold at least one active compound in each layer. They might also be fabricated as ultra-disintegrated fibrous films for oral cavity administration, i.e., buccal or sublingual, to improve the bioavailability and intake of the administered drugs. Therefore, in this work, a combination of nifedipine and atorvastatin calcium, which are frequently prescribed for hypertension and hyperlipidemia patients, respectively, was prepared in a coaxial electrospinning system for buccal administration. Scanning electron microscopy image showed the successful preparation of smooth, non-beaded, and non-porous surfaces of the drug-loaded nanofibers with an average fiber diameter of 968 ± 198 nm. In contrast, transmission electron microscopy distinguished the inner and outer layers of those nanofibers. The disintegration of the drug-loaded nanofibers was ≤12 s, allowing the rapid release of nifedipine and atorvastatin calcium to 61% and 47%, respectively, after 10 min, while a complete drug release was achieved after 120 min. In vitro, a drug permeation study using Franz diffusion showed that the permeation of both drugs from the core-shell nanofibers was enhanced significantly (p < 0.05) compared to the drugs in a solution form. In conclusion, the development of drug-loaded nanofibers containing nifedipine and atorvastatin calcium can be a potential buccal delivery system.

Keywords: buccal delivery; coaxial electrospinning; core–shell nanofibers; fast-dissolving fibers.

Figure 1

SEM image (a) and fibers diameter distribution (b) of the drug-loaded core–shell nanofibers, showing smooth, non-beaded, and non-porous surfaces of the fibers, with an average diameter of 968 ± 198 nm.

Figure 2

TEM image of drug-loaded core–shell nanofibers showing two distinct layers. The red and green arrows represent the inner and outer layers of the nanofibers, respectively.

Figure 3

XRD patterns of PVP, nifedipine, atorvastatin calcium, PM, blank and drug-loaded nanofibers showing that both drugs were in the crystalline form (presence of characteristic reflections), while PVP was in the amorphous form (broad halo pattern). The presence of the drugs’ distinct peaks was presented in the PM but was absent in the drug-loaded nanofibers, suggesting the molecular dispersion of the drugs due to the electrospinning process.

Figure 4

FTIR transmissions at (a) a full wavenumber range (4000 to 600 cm⁻¹), and (b) more focused range (2000 to 600 cm⁻¹) of PVP, nifedipine, atorvastatin calcium, PM, blank and drug-loaded nanofibers showed the distinctive drugs’ peaks at 1493 cm⁻¹ and 1509 cm⁻¹ that appeared in the PM and drug-loaded nanofibers but not in the blank nanofibers.

Figure 5

The disintegration of (a) blank fibers and (b) drug-loaded fibers shows that the blank fiber disintegrated and dissolved more rapidly (≤2 s) than the drug-loaded fibers (≤12 s). The yellow color in the drug-loaded nanofibers indicates the encapsulation of nifedipine.

Figure 6

The release profile of the drug-loaded core–shell fibers of nifedipine and atorvastatin calcium showed a burst release at 10 min, followed by >80% release after 30 min and a complete drug release after 120 min—results represented as mean ± SD (n = 3).

Figure 7

The permeability of (a) nifedipine and (b) atorvastatin calcium in drug-loaded nanofibers and in drug solution form. The results showed a significantly enhanced permeability (p < 0.05) for both drugs from the nanofibers compared to the solution form—results represented as mean ± SD (n = 3).

Figure 7

The permeability of (a) nifedipine and (b) atorvastatin calcium in drug-loaded nanofibers and in drug solution form. The results showed a significantly enhanced permeability (p < 0.05) for both drugs from the nanofibers compared to the solution form—results represented as mean ± SD (n = 3).

Figure 8

Cell viability of different concentrations of atorvastatin, nifedipine, and their 1:1 combination upon 24 h exposure with HFF-1 cells. The data showed that nifedipine is safer (≤500 µg/mL) than atorvastatin calcium (<30 µg/mL), while it is only safe <15 µg/mL for the combination—results represented as mean ± SD (n = 3).