RESEARCH ARTICLE
Electrodeless Electrohydrodynamic Drop-on-Demand
Encapsulation of Drugs into Porous Polymer Films for Fabrication
of Personalized Dosage Units
EZINWA ELELE,
1
YUEYANG SHEN,
1
RAMANA SUSARLA,
1
BORIS KHUSID,
1
GOLSHID KEYVAN,
2
BOZENA MICHNIAK-KOHN
2
1
Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark,
New Jersey 07102
2
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway,
New Jersey 08854
Received 5 December 2011; revised 26 March 2012; accepted 4 April 2012
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.23165
ABSTRACT: Noncontact drop-on-demand (DOD) dosing is a promising strategy for manu-
facturing of personalized dosage units. However, current DOD methods developed for printing
chemically and thermally stable, low-viscosity inks are of limited use for pharmaceuticals due
to fundamentally different functional requirements. To overcome their deficiency, we developed
a novel electrohydrodynamic (EHD) DOD (Appl, Phys, Lett. 97, 233501, 2010) that operates on
fluids of up to 30 Pa·s in viscosity over a wide range of droplet sizes and provides a precise
control over the droplet volume. We now evaluate the EHD DOD as a method for fabrication
of dosage units by printing drug solutions on porous polymer films prepared by freeze-drying.
Experiments were carried out on ibuprofen and griseofulvin, as model poorly water-soluble
drugs, polyethylene glycol 400, as a drug carrier, and hydroxypropyl methylcellulose films. The
similarities between drug release profiles from different dosage units were assessed by model-
independent difference, f
1
, and similarity, f
2
, factors. The results presented show that EHD
DOD offers a powerful tool for the evolving field of small-scale pharmaceutical technologies for
tailoring medicines to individual patient’s needs by printing a vast array of predefined amounts
of therapeutics arranged in a specific pattern on a porous film. © 2012 Wiley Periodicals, Inc.
and the American Pharmacists Association J Pharm Sci
Keywords: Processing; solid dosage form; drug delivery systems; encapsulation; freeze-
drying; dissolution rate
INTRODUCTION
Studies conducted over the past two decades indicate
that a substantial portion of drug response variabil-
ity is genetically determined.
1–3
These observations
have given rise to the concept of personalized therapy
whose ultimate goal is to develop medicinal agents
designed for each niche of the population and/or in-
dividual patients according to the vagaries and vari-
ance of their genes.
1–3
Under a personalized medicine
scheme, drug prescribing and dosing should be care-
fully tailored to a patient’s genetic background. How-
Additional Supporting Information may be found in the online
version of this article. Supporting Information
Correspondence to: Boris Khusid (Telephone: 1-973-596-3316;
Fax: 1-973-596-8436; E-mail: khusid@adm.njit.edu)
Journal of Pharmaceutical Sciences
© 2012 Wiley Periodicals, Inc. and the American Pharmacists Association
ever, the existing pharmaceutical technologies for
dosage unit production, which have evolved around
large-scale manufacturing of solid dosage forms, can-
not address needs of individual patients. Noncon-
tact drop-on-demand (DOD) dosing (i.e., droplets are
formed only as required) is considered as a promis-
ing strategy for the development of novel technolo-
gies to make small-scale manufacturing of personal-
ized medicines to be economically viable. DOD print-
ing, which is commonly used in graphic arts, has re-
cently drawn great scientific and industrial interest
as a rapid and low-cost fabrication technique for a
wide range of novel applications,
4
such as transis-
tor circuits, functional ceramics, cell patterns, scaf-
folds, and pharmaceutical dosage forms. As a digital
technology, computer-controlled DOD dosing is able
to form a personalized dosage unit and reduce drug
waste by printing a vast array of predefined amounts
JOURNAL OF PHARMACEUTICAL SCIENCES 1