Fabrication of printed drug-delivery systems Natalja Genina(1), Ruzica Kolakovic(1), Mirja Palo (1), Daniela Fors(2), Helka Juvonen(2), Petri Ihalainen(2), Jouko Peltonen(2), Niklas Sandler(1)

(1)Pharmaceutical Sciences Laboratory, Department of Biosciences, Abo Akademi University, Turku, Finland, (2) Center of Excellence for Functional Materials, Laboratory of Physical Chemistry, Abo Akademi University, Turku, Finland

Abstract

Printing technologies specifically digital inkjet printing, offer possibilities in the production of individualized medicines. The main advantage of inkjet printing includes the ability to dispense uniform droplets in the picoliter range with high degree of accuracy to allow dose personalization. The pharmaceutical ink formulation has to be designed with respect to its viscosity and surface tension to guarantee continuous printing and high reproducibility of the forming droplets to allow dose uniformity. The aim of this paper is demonstrate the combined use of inkjet and flexographic printing to fabricate pharmaceutical solid dosage forms with controlled release properties of drug substances. Also the characterization of substrates and final drug-delivery systems is studied with various techniques and discussed.

Introduction Printing technologies such as inkjet and flexographic printing,

offer possibilities in the production of more individualized medicine. The main advantage of inkjet printing includes the ability to dispense uniform droplets in the picoliter range with high degree of accuracy to allow dose personalization [1]. The pharmaceutical ink formulation has to be designed with respect to its viscosity and surface tension to guarantee continuous printing and high reproducibility of the forming droplets to allow dose uniformity. During the last decade, this technology has opened new perspectives when designing individual dosage forms. Inkjet printing to directly deposit drug solutions or suspensions containing active pharmaceutical ingredients (API) and excipients onto carrier materials such as porous substrates and biodegradable films, offers innovative ways for fabrication of oral solid dosage forms with controlled physical properties of the API. Recently, drug release profiles have been altered by inkjet printing of API(s) and polymer(s) mixtures at different molar ratios. The aim of this work was to demonstrate the combined use of inkjet and flexographic printing to fabricate pharmaceutical solid dosage forms with controlled release properties of drug substances as described in [2]. A different range of analytical techniques were used and evaluated to characterize the substrates and final dosage forms.

Materials and methods

Model drugs and substrates In the study we used riboflavin sodium phosphate (RSP) and

propranolol hydrochloride (PH) as theophylline (TH) model drugs. Three different types substrates were used as porous model carriers

for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer. The printed APIs were coated with water insoluble ethylcellulose (EC) films of different thickness using flexographic printing. Two ink formulations formulated to print the drug substances on the substrates. The propranolol containing ink was prepared by dissolving 50 mg/ml propranolol powder in PG:water mixture (30:70, vol%). The RSP containing ink was made by mixing 31.5 mg/ml of RSP powder with glycerol:ethanol:water (10:10:80, vol%). The ink solutions were filtered with 0.45 lm and 0.2 lm polypropylene membrane filters (WhatmanTM, GE Healthcare, Piscataway, NJ, USA) before printing. The polymeric coating solution for flexography was prepared by dissolving 5% (wt%) EC in ethanol under continuous stirring [2].

Printing Theophylline printing experiments were performed with an

unmodified Canon thermal inkjet printer (Pixma MP495, Canon Inc., Japan). Inkjet printing for PH and RSP was performed with a Dimatix DMP-2800 inkjet printer (Fujifilm Dimatix Inc., Santa Clara, California). A MEMS-based cartridge-styled printhead with 16 nozzles linearly spaced at 254 lm that produce a typical drop size of 10 pl was used. Each cartridge could hold 1.5 ml of ink. Printing was performed in ambient conditions at 45.5±5% relative humidity (RH) and 21 ± 1 °C with a single nozzle (20 micron orifice diameter) at firing voltages of 30 V and 35 V for PH and RSP, respectively. The cartridge temperature was 30 °C, and the drops were deposited at a drop spacing of 10 micrometers. The drugs were printed in squares (n = 10–20 for each paper substrate and ink formulation) of 1 cm x 1 cm, making according to the Dimatix software the total number of drops in one square equal to 1,002,001, which theoretically correspond to approximately 10.02 microliters per cm squared, when assuming a drop volume of 10 pl.

Dissolution and content uniformity The dissolution rate of API from the paper substrates was

studied by using USP paddle method. 500 ml of purified water was used as a dissolution medium. The paper samples were put in spiral capsule sinkers to prevent floating. For content uniformity measurements the printed drug areas on the substrates were immersed into 50 ml of 0.1 N HCl. The volumetric flasks were shaken vigorously and were let to stay for 1 h. Consequently, the absorbance of the obtained solutions was measured at 220 nm for

236 ©2013; Society for Imaging Science and Technology

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