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Case studies

Drying of large molecules at ambient temperature

Biologics have enjoyed a rapid expansion over the past decade and are currently one of the fastest growing segments of the pharmaceutical industry market. In liquid dosage forms, biologics often show instability due to being prone to physical and chemical degradation. Therefore, the development of solid biopharmaceutical products that retain their initial activity can be a milestone in the commercialization of biopharmaceuticals. The elimination of water from the formulations improves the stability with additional benefits being reduced transportation costs and easier handling and storage. However, biologics are usually very sensitive due to their structural complexity, and therefore, the use of mild conditions during their drying is extremely important.

 

Electrospinning is a continuous process with low energy consumption that enables the drying of sensitive biologics at room temperature. These features make electrospinning a promising alternative technology to freeze drying.

Experiment with infliximab

  • Infliximab: TNF-α neutralizing IgG monoclonal antibody against IBD, rheumatoid arthritis, psoriasis, etc.

  • Fast-dissolving fibrous reconstitution powder was prepared by high-speed electrospinning at room temperature

  • No significant aggregation of the monoclonal antibody was detected after electrospinning

Large scale fiber production was carried out with a cyclodextrin matrix that can stabilize proteins.

Size exclusion chromatography showed 99.24% monomer content following electrospinning.

The reconstitution test resulted in a complete dissolution of the fibers within 2 minutes.

Enhancing dissolution and bioavailability of BCS II drugs

Today, approximately 70% of the drug candidates in contemporary pipelines have poor solubility and about 40% of drugs are categorized as insoluble. These substances usually belong to the BCS (biopharmaceutical classification system) class II meaning that their bioavailability is limited by solubility or dissolution rate. Amorphous solid dispersions (ASDs) have become an established platform to address these issues due to the higher apparent solubility of the APIs in their amorphous form.

Electrospinning is a novel method to prepare ASDs or nano-ASDs. The drying time of the electrospun fibers (<1 s) is generally significantly shorter than in the case of spray dried particles. This leads to better amorphization and faster dissolution of electrospun materials compared to sprayed powders.

Dissolution enhancement of itraconazole

  • Itraconazole: BCS II antifungal drug

  • Scaled-up production of fibers with exceptional dissolution was carried out

  • 250 000 number of doses can be produced in one week at pilot scale

X-ray powder diffraction and differential scanning calorimetry measurements showed that the API is fully amorphous in the fibers.

Electrospun fibers exhibited faster dissolution compared to the spray dried powder with the same composition.

Bioavailability enhancement of flubendazole

  • Flubendazole: BCS II anthelmintic drug

  • Electrospun formulation had remarkably enhanced oral bioavailability

  • Preparation of minitablets from electrospun fibers is possible

    • Minitablets are suitable for animal studies (e.g. toxicology and in vivo PK studies)

    • Very similar to human dosage form

In comparison with the very slow in vitro dissolution of crystalline flubendazole, the drug release was rapid from the electrospun formulations.

The fibrous system showed a significantly higher blood level profile than the microcrystalline API in rats.

Ultrafast dissolution of the fibers/particles

The large surface area of the electrospun fibers makes them suitable for fast dissolving drug dosage forms like oral thin films, orodispersible tablets, mucoadhesive patches, etc. These dosage forms have a number of advantages including

  • instant drug release and rapid onset action (e.g. against migraine);

  • site-specific effect (e.g. sore throat);

  • buccal adsorption, avoidance of first pass effect;

  • improved oral bioavailability;

  • chance for reformulation of existing drugs (product life-cycle management, market competition).

Development of Donepezil HCl film

  • Donepezil HCl: Small molecule used as Alzheimer’s disease treatment

  • In vitro drug release of the electrospun films was immediate (less than 30 s)​

Drug loaded orally dissolving electrospun film

Cast films with the same compositions as the fibers and commercial tablets needed 30 min or more for complete dissolution

Instranasal vaccine delivery

  • Promising alternative administration route for vaccines

  • Solid form is more stable than liquid form – easier and cheaper storage and transport

  • Advantages:

    • Intranasal vaccination induces a more similar immune response to neutral infection than intramuscular delivery

    • Simpler vaccination procedure

    • Suitable for mass vaccination

    • No needles and skilled personnel required

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