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

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.

Skin Permeation of Nanoparticles: Mechanisms Involved and Critical Factors Governing Topical Drug Delivery.

Transdermal route has been an ever sought-after means of drug administration, regarded as being the most convenient and patient compliant. However, skin poses a great barrier to the entry of the external particles including bacteria, viruses, allergens, and drugs as well (mostly hydrophilic or high molecular weight drugs), consequent to its complex structure and composition. Among the various means of enhancing drug permeation through the skin, e.g. chemical permeation enhancers, electroporation, thermophoresis, etc. drug delivery through nanoparticles has been of great interest. Current literature reports a vast number of nanoparticles that have been implicated for drug delivery through the skin. However, a precise account of critical factors involved in drug delivery and mechanisms concerning the permeation of nanoparticles through the skin is necessary. The purpose of this review is to enumerate the factors crucial in governing the prospect of drug delivery through skin and classify the skin permeation mechanisms of nanoparticles. Among the various mechanisms discussed are the ones governed by principles of kinetics, osmotic gradient, adhesion, hydration, diffusion, occlusion, electrostatic interaction, thermodynamics, etc. Among the most common factors affecting skin permeation of nanoparticles that are discussed include size, shape, surface charge density, composition of nanoparticles, mechanical stress, pH, etc.