Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients

ABSTRACT

Purpose

To investigate the use of electrospinning for forming solid dispersions containing crystalline active pharmaceutical ingredients (API) and understand the relevant properties of the resulting materials.

Method

Free surface electrospinning was used to prepare nanofiber mats of poly(vinyl pyrrolidone) (PVP) and crystalline albendazole (ABZ) or famotidine (FAM) from a suspension of the drug crystals in a polymer solution. SEM and DSC were used to characterize the dispersion, XRD was used to determine the crystalline polymorph, and dissolution studies were performed to determine the influence of the preparation method on the dissolution rate.

Results

The electrospun fibers contained 31 wt% ABZ and 26 wt% FAM for the 1:2 ABZ:PVP and 1:2 FAM:PVP formulations, respectively, and both APIs retained their crystalline polymorphs throughout processing. The crystals had an average size of about 10 μm and were well-dispersed throughout the fibers, resulting in a higher dissolution rate for electrospun tablets than for powder tablets.

Conclusions

Previously used to produce amorphous formulations, electrospinning has now been demonstrated to be a viable option for producing fibers containing crystalline API. Due to the dispersion of the crystals in the polymer, tablets made from the fiber mats may also exhibit improved dissolution properties over traditional powder compression.

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Abbreviations

ABZ:

albendazole

API:

active pharmaceutical ingredient

DSC:

differential scanning calorimetry

FAM:

famotidine

PVP:

poly(vinyl pyrrolidone)

SEM:

scanning electron microscopy

XRD:

X-ray diffraction

A :

surface area for diffusion

C :

concentration in solution

C sat :

solubility

D :

diffusion coefficient

\( \frac{{dm}}{{dt}} \) :

dissolution rate

g :

gravitational acceleration

h :

diffusional path length

ρ f :

density of the fluid

ρ p :

density of the particle

R :

radius of the particle

μ :

viscosity of the fluid

v s :

settling velocity

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ACKNOWLEDGMENTS AND DISCLOSURES

We would like to acknowledge Novartis AG for funding and support of this work. We would also like to thank Keith M. Forward for aid with free-surface electrospinning and Keith Chadwick for his input on XRD interpretation.

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Correspondence to Bernhardt L. Trout.

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Brettmann, B.K., Cheng, K., Myerson, A.S. et al. Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients. Pharm Res 30, 238–246 (2013). https://doi.org/10.1007/s11095-012-0868-4

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KEY WORDS

  • crystals
  • electrospinning
  • formulation
  • solid dispersion