Optimizing the fabrication of electrospun nanofibers of prochlorperazine for enhanced dissolution and permeation properties

Hasham Shafi; D V Siva Reddy; Rumaisa Rashid; Trisha Roy; Shabnam Kawoosa; G N Bader; Chakradhar Jvus; Abdalla Abdal-Hay; Mushtaq A Beigh; Shafquat Majeed; Nisar Ahmad Khan; Faheem A Sheikh

doi:10.1016/j.bioadv.2024.213773

Optimizing the fabrication of electrospun nanofibers of prochlorperazine for enhanced dissolution and permeation properties

Biomater Adv. 2024 Apr:158:213773. doi: 10.1016/j.bioadv.2024.213773. Epub 2024 Jan 18.

Authors

Affiliations

¹ Nanostructured and Biomimetic Lab, Department of Nanotechnology, University of Kashmir, Srinagar 190006, Jammu and Kashmir, India; Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India; CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India.
² CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India.
³ Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India; CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India.
⁴ Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India.
⁵ Faculty of Industry and Energy Technology, Mechatronics Technology Program, New Cairo Technological University, New Cairo - Fifth Settlement, Cairo 11835, Egypt; Department of Engineering Materials and Mechanical Design, Faculty of Engineering, South Valley University, Qena 83523, Egypt; The University of Queensland, School of Dentistry, Oral Health Centre Herston, 288 Herston Road, Herston, QLD 4006, Australia; Cellular Signalling and Nanotherapeutics Laboratory, Department of Nanotechnology, University of KashmirHazratbal, Srinagar, Jammu and Kashmir, India.
⁶ Cellular Signalling and Nanotherapeutics Laboratory, Department of Nanotechnology, University of KashmirHazratbal, Srinagar, Jammu and Kashmir, India.
⁷ Laboratory for Multifunctional Nanomaterials, Department of Nanotechnology, University of Kashmir Hazratbal, Srinagar, Jammu and Kashmir 190006, India.
⁸ Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India. Electronic address: nakhan2008@gmail.com.
⁹ Nanostructured and Biomimetic Lab, Department of Nanotechnology, University of Kashmir, Srinagar 190006, Jammu and Kashmir, India. Electronic address: faheemnt@uok.edu.in.

PMID: 38277903
DOI: 10.1016/j.bioadv.2024.213773

Abstract

Despite being an approved antiemetic for more than five decades, the clinical usefulness of prochlorperazine is limited by its low solubility and inconsistent absorption in the gastrointestinal tract, which presents challenges for nanotherapeutic interventions. Here, we report the preparation of a highly soluble and permeable nanofiber formulation of prochlorperazine using the Quality-by-Design approach. The final nanofiber formulation with drug entrapment of 88.02 ± 1.14 % was obtained at 20.0 kV, with a flow rate of 0.5 ml/h and tip-to-collector distance of 19.9 cm. Physio-mechanical properties, such as thickness (0.42 ± 0.02 mm), pH resistance (7.04 ± 0.08), folding endurance (54 ± 5), and tensile strength (0.244 ± 0.02 N.mm^-2), were appropriate for packaging and application to oromucosal surfaces. The content uniformity (93.48-106.63 %) and weight variation (<1.8 mg) of the optimal nanofiber formulation were within the permissible limits prescribed for orodispersible films. Microscopical investigations confirm a randomly deposited and dense network of woven nanofibers with an average diameter of 363 ± 5.66 nm. The drug particles were embedded homogeneously on the fiber in the nanoform (4.27 ± 1.34 nm). The spectral analysis using TEM-EDS shows diffraction peaks of sulfur and chlorine, the elemental constituents of prochlorperazine. The drug was amorphized in the nanofiber formulation, as led by the decline of the crystallinity index from 87.25 % to 7.93 % due to electrostatic destabilization and flash evaporation of the solvent. The enthalpy of fusion values of the drug in the nanofiber mat decreased significantly to 23.6 J/g compared to its pristine form, which exhibits a value of 260.7 J/g. The nanofibers were biocompatible with oral mucosal cells, and there were no signs of mucosal irritation compared to 1 % sodium lauryl sulfate. The fiber mats rapidly disintegrated within <1 s and released ≈91.49 ± 2.1 % of the drug within 2 min, almost 2-fold compared to the commercial Stemetil MD® tablets. Similarly, the cumulative amount of the drug permeated across the unit area of the oromucosal membrane was remarkably high (31.28 ± 1.30 μg) compared to 10.17 ± 1.11 μg and 13.10 ± 1.79 μg from the cast film and drug suspension. Our results revealed these nanofiber formulations have the potential to be fast-dissolving oromucosal delivery systems, which can result in enhanced bioavailability with an early onset of action due to rapid disintegration, dissolution, and permeation.

Keywords: Drug flux; Fast dissolving delivery system; Prochlorperazine; Rapid disintegration.

MeSH terms

Nanofibers*
Prochlorperazine*
Solubility

Substances

Prochlorperazine