Abstract
We demonstrate the ability to fabricate dosage forms of a poorly water-soluble drug by using wet stirred media milling of a drug powder to produce an aqueous suspension of nanoparticles and then print it onto a porous biocompatible film. Contrary to conventional printing technologies, a deposited material is pulled out from the nozzle. This feature enables printing highly viscous materials with a precise control over the printed volume. Drug (griseofulvin) nanosuspensions prepared by wet media milling were printed onto porous hydroxypropyl methylcellulose films prepared by freeze-drying. The drug particles retained crystallinity and polymorphic form in the course of milling and printing. The versatility of this technique was demonstrated by printing the same amount of nanoparticles onto a film with droplets of different sizes. The mean drug content (0.19–3.80 mg) in the printed films was predicted by the number of droplets (5–100) and droplet volume (0.2–1.0 µL) (R2 = 0.9994, p-value < 10−4). Our results also suggest that for any targeted drug content, the number-volume of droplets could be modulated to achieve acceptable drug content uniformity. Analysis of the model-independent difference and similarity factors showed consistency of drug release profiles from films with a printed suspension. Zero-order kinetics described the griseofulvin release rate from 1.8% up to 82%. Overall, this study has successfully demonstrated that the electro-hydrodynamic drop-on-demand printing of an aqueous drug nanosuspension enables accurate and controllable drug dosing in porous polymer films, which exhibited acceptable content uniformity and reproducible drug release.
Highlights
The precision medicine approach uses methods of molecular analysis to tailor the specific drug and dose strength to a patient’s genetic background [1,2]
Suspensions were printed on circular cuts made with a 5/8” (15.88 mm) diameter punch (O’Brien Consolidated Industries, Lewiston, ME, USA) from porous hydroxypropyl methylcellulose (HPMC) films prepared by freeze-drying of an aqueous solution
We have demonstrated that the EHD DOD method [18] can be used to fabricate dosage forms by encapsulating Biopharmaceutical Classification System (BCS) Class II drug nanoparticles into porous polymer films
Summary
The precision medicine approach uses methods of molecular analysis to tailor the specific drug and dose strength to a patient’s genetic background [1,2]. The transformation of health care from one-size-fits-all to a targeted approach utilizing each patient’s molecular information is accelerating as the U.S Food and Drug Administration (FDA) continues to rapidly approve new precision diagnostic tools and treatments. The conventional large-scale pharmaceutical manufacturing systems cannot cost-effectively address the needs of individual patients. Key challenges that the pharmaceutical products, manufacturing systems, drug supply chain, and healthcare professional would have to address in order to support individualization of dosage forms were thoroughly discussed in [4,5,6,7,8]
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