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. 2020 May 21;12(5):470.
doi: 10.3390/pharmaceutics12050470.

Electrospun Orodispersible Films of Isoniazid for Pediatric Tuberculosis Treatment

Konstantina Chachlioutaki  1 , Emmanouil K Tzimtzimis  2 , Dimitrios Tzetzis  2 , Ming-Wei Chang  3 , Zeeshan Ahmad  4 , Christina Karavasili  1 , Dimitrios G Fatouros  1
Affiliations

Electrospun Orodispersible Films of Isoniazid for Pediatric Tuberculosis Treatment

Konstantina Chachlioutaki et al. Pharmaceutics. .

Abstract

Child-appropriate dosage forms are critical in promoting adherence and effective pharmacotherapy in pediatric patients, especially those undergoing long-term treatment in low-resource settings. The present study aimed to develop orodispersible films (ODFs) for isoniazid administration to children exposed to tuberculosis. The ODFs were produced from the aqueous solutions of natural and semi-synthetic polymer blends using electrospinning. The spinning solutions and the resulting fibers were physicochemically characterized, and the disintegration time and isoniazid release from the ODFs were assessed in simulated salivary fluid. The ODFs comprised of nanofibers with adequate thermal stability and possible drug amorphization. Film disintegration occurred instantly upon contact with simulated salivary fluid within less than 15 s, and isoniazid release from the ODFs in the same medium followed after the disintegration profiles, achieving rapid and total drug release within less than 60 s. The ease of administration and favorable drug loading and release properties of the ODFs may provide a dosage form able to facilitate proper adherence to treatment within the pediatric patient population.

Keywords: electrospinning; isoniazid; orodispersible films; pediatric drug delivery; tuberculosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Viscosity as a function of shear rate for the pullulan solution and its blends with increasing concentrations of (A) HPMC, (B) pectin and (C) sodium caseinate.
Figure 2
Figure 2
(A) and (C) SEM images of the ODF formulations containing (a) pullulan, (b) pullulan/HPMC 3%, (c) pullulan/HPMC 2%, (d) pullulan/HPMC 1%, (e) pullulan/pectin 3%, (f) pullulan/pectin 2%, (g) pullulan/pectin 1%, (h) pullulan/NaCas 3%, (i) pullulan/NaCas 2%, (j) pullulan/NaCas 1% and (k) pullulan-ISO, (l) pullulan/HPMC 3%-ISO, (m) pullulan/HPMC 2%-ISO, (n) pullulan/HPMC 1%-ISO, (o) pullulan/pectin 3%-ISO, (p) pullulan/pectin 2%-ISO, (q) pullulan/pectin 1%-ISO, (r) pullulan/NaCas 3%-ISO, (s) pullulan/NaCas 2%-ISO and (t) pullulan/NaCas 1%-ISO and their respective diameter distributions (B). (a–j) and (D). (k–t). Scale bar: 10 μm.
Figure 3
Figure 3
DSC thermograms of the (A) raw materials, (B) plain ODFs and (C) ISO-loaded ODFs.
Figure 4
Figure 4
TGA curves of the (A) raw materials, (B) plain ODFs and (C) ISO-loaded ODFs.
Figure 5
Figure 5
FTIR spectra of the (A) raw materials, the plain ODFs containing (B) HPMC, (C) pectin and (D) NaCas, and the ISO-loaded ODFs containing (E) HPMC, (F) pectin and (G) NaCas.
Figure 6
Figure 6
In vitro disintegration profiles of the ODFs in simulated salivary fluid as a function of time.
Figure 7
Figure 7
In vitro drug release profiles of ISO from the ODFs in simulated salivary fluid pH 7.0 at 37 °C.
See this image and copyright information in PMC

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