Fabricating transdermal film formulations of montelukast sodium with improved chemical stability and extended drug release

Abstract

Montelukast Sodium (MK) is a leukotriene receptor antagonist, an oral drug generally prescribed to control chronic asthma symptoms. This research aims to provide the transdermal delivery of this drug in a controlled release profile as a better mode of drug delivery, specifically for the pediatric and elderly population. Transdermal delivery of the drug not only improves the drug's bioavailability but also maintains the concentration of the drug in the plasma without increasing the frequency of the drug dosage. Transdermal film formulations were developed using sodium alginate (SA) and lignosulphonic acid (LS) as the matrix and PEG-400 or Glycerine (Gly) as the plasticizers. Various physiochemical characteristic evaluations of the formulated films were conducted, revealing that the formulation with Glycerine as the plasticizer had a smooth surface and was flexible. It was observed that this formulation had the highest moisture uptake capacity and the lowest moisture loss capacity when compared with the other two formulations. It was also observed that the barium chloride cross-linked formulation had a higher swelling index when compared with calcium chloride cross-linked films. The surface pH of all the formulations was monitored to be around 7.5. In the in vitro release studies, the cross-linked films showed a controlled release over 36 h compared with the non-cross-linked films. Based on the observations and results, the cross-linked film formulation showed a better-controlled release of the drug and could potentially increase its bioavailability. TGA analysis of the polymeric mixture demonstrated the thermal stability of the SA blends, which enhanced the flexibility of the SALS blend with Glycerine. XRD of samples confirmed the amorphous nature of SALS blends with Gly, which influences the flexibility of the blend. The blends are further investigated for morphology using SEM to test their compatibility with the drug.

Keywords: Eggshell; Lignosulphonic acid; Montelukast sodium; Polymer blends; Sodium alginate; Transdermal drug delivery.

Fig. 1

Route of Montelukast Sodium when delivered transdermally.

Fig. 2

The diagram depicts the preparation steps of the Montelukast Sodium loaded transdermal films.

Fig. 3

Transdermal drug-loaded film: (A) SALS/MK, (B) SALS/PEG-400/MK (C) SALS/Gly/MK.

Fig. 4

FT-IR Sample pellets of (A) SA/LS/MK (B) SA/LS/MK/PEG (C) SA/LS/MK/Gly (D) Montelukast Sodium (MK) (E) SA/LS/Gly.

Fig. 5

Calibration curve of montelukast sodium.

Fig. 6

Isolation of Egg Membrane: (a) Egg kept in Hydrochloric acid (b) Isolated Egg Membrane.

Fig. 7

In vitro drug release setup: The diagram depicts the drug release setup, which includes the donor compartment with the opening covered with the polymeric film and the egg membrane. The donor compartment is dipped into the receptor compartment containing acetate buffer.

Fig. 8

Graphs depict the FT-IR studies of the drug and different polymer blend combinations.

Fig. 9

Graphs depict the XRD studies of the drug and different polymer blend combinations.

Fig. 10

TGA graphs of the drug and different polymer blend combinations. a)SALS b)SALS/MK c)SALSPEGMK d)SALSGLYMK e)SALSGLY

Fig. 11

SEM images of a) SALS/MK (MK1). b) SALS/PEG/MK(MK2). c) SALS/Gly/MK (MK3).

Fig. 12

Moisture uptake and moisture loss studies by formulated films in a desiccator containing: (a) Calcium Chloride for moisture loss studies (b) Sodium Chloride for moisture uptake studies.

Fig. 13

Swelling Index studies: (A–C) Calcium Chloride cross-linked films after swelling index studies up to 3 h of S1 film, P1 film and G1 film, respectively. (D–F) Barium Chloride cross-linked films after swelling index studies up to 3 h of S3 film, P3 film and G3 film, respectively.

Fig. 14

UV Plots for release of MK drug for various intervals (a) Non-cross-linked SA/LS film (b) The CaCl₂ cross-linked SA/LS film (c) The BaCl₂ cross-linked SA/LS film (d) Overall release of MK drug.

Fig. 15

UV Plots of SALS-Gly for MK drug release at various intervals (a) The non-cross-linked film (b) The CaCl₂ cross-linked film (c) The BaCl₂ cross-linked film (d)The graph of the overall release of MK drug.

Fig. 16

The UV spectra of the release of the MK drug from SALS-PEG film at various intervals (a) The non-cross-linked film (b) The CaCl₂ cross-linked film (c) The BaCl₂ cross-linked film (d) The graph of the overall release of MK drug from all the SA/LS/Gly film variations.