A Comprehensive Review of Patented Technologies to Fabricate Orodispersible Films: Proof of Patent Analysis (2000-2020)

Abstract

Orodispersible films (ODFs)are ultra-thin, stamp-sized, rapidly disintegrating, and attractive oral drug delivery dosage forms best suited for the pediatric and geriatric patient populations. They can be fabricated by different techniques, but the most popular, simple, and industrially applicable technique is the solvent casting method (SCM). In addition, they can also be fabricated by extrusion, printing, electrospinning, and by a combination of these technologies (e.g., SCM + printing). The present review is aimed to provide a comprehensive overview of patented technologies of the last two decades to fabricate ODFs. Through this review, we present evidence to adamantly confirm that SCM is the most popular method while electrospinning is the most recent and upcoming method to fabricate ODFs. We also speculate around the more patent-protected technologies especially in the domain of printing (two or three-dimensional), extrusion (ram or hot-melt extrusion), and electrospinning, or a combination of the methods thereof.

Keywords: electrospinning; orodispersible films; printing technologies; solvent casting.

Figure 19

Flexographic printing:(A) flexo process showing micrographs of anilox roller and nip area between the printing cylinder and impression cylinder [101]; (B) flexo printing with online monitoring—Adapted with permission from reference [101], 2013, Elsevier. All images reprinted with permission from respective publishers.

Figure 1

Classification of orodispersible films (ODFs) [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23].

Figure 2

Identification of patent citations using LENS (free online patent database).

Figure 3

History of Orodispersible films (ODFs) (A) prior to 2000 (B) over the counter (OTC) products as thin films (2001 to 2009) (C) prescription-Rx-products as thin films (2010 to 2020).

Figure 4

Steps in fabrication of orodispersible films by solvent casting method.

Figure 5

Inaccuracies inorodispersible films fabricated by solvent casting method.

Figure 6

Thermal gelling point (a) heating the mixture at higher thermal gelation temperature (TGel) leads to formation of air bubbles in the film (b) employing gelling aids reduces the TGel and reduces formation of air bubbles in the film.

Figure 7

PharmFilm technology to fabricate orodispersible films. Reprinted with permission from [40], 2021, Elsevier.

Figure 8

Fabrication of perforated orodispersible films.

Figure 9

Structuredorodispersible films (SOFTs) and its preparation [66]. Adapted with permission from [66], 2019, Elsevier.

Figure 10

Hot-melt extrusion: (A) different extruders and types; (B) counter rotating and co-rotating screws; (C) different zones on a modular screw; (D) process to fabricate orodispersible films (ODFs) by the HME method.

Figure 11

Common limitations of hot-melt extrusion method.

Figure 12

Orodispersible film scale-up by hot-melt extrusion method: (A) small scale extrusion—ODF composition can be directly feed into the hopper from the feeder; (B) medium scale extrusion—ODF composition of solid blend can be feed from one side and the flavor/plasticizers can be feed from the other side; (C) large scale extrusion—depending on the type of ingredients employed in ODF preparation—they can be feed separately from respective feeders to the hopper; (D) extrusion process with optional compression rollers and heated rollers to fabricate oral films of nicotine/snuff (tobacco)—Adapted from [85].

Figure 13

Basic setup of the electrospinning process.

Figure 14

Nanospider technology: (A) stationary-wire electrospinning; (B) Elmarco’s commercialized Nanospider technology showing nanofiber web on the substrate, stationary wire with polymer solution on the wire and nanofiber formation, stationary wire electrode system and nanofiber formation when fully operational. Image courtesy: Elmarco.

Figure 15

PatentedElectrospinning by (A) solution method; (B) suspension method.

Figure 16

Inkjet printing of orodispersible films showing different print heads, printed ODF and mechanism of ink ejection onto the edible substrate and drying to obtain ODFs.

Figure 17

Common limitations of printing methods.

Figure 18

Ink-jet printing: (A) printer head dispensing/printing the drug containing ink into the blister cavities; (B) top view of the blister packs with inkjet printed ODFs having each dose separated by a separation line; (C) individual packaging unit showing a flexible sheet and the packed film—showing zones of deformity during the opening of the film—Adapted from [99].

Figure 20

Scientific prospection using PubMed.