Polymer strip films as a robust, surfactant-free platform for delivery of BCS Class II drug nanoparticles.

The robustness of the polymer strip film platform to successfully deliver a variety of BCS Class II drug nanoparticles without the need for surfactant while retaining positive characteristics such as nanoparticle redispersibility and fast dissolution is demonstrated. Fenofibrate (FNB), griseofulvin (GF), naproxen (NPX), phenylbutazone (PB), and azodicarbonamide (AZD) were considered as model poorly water-soluble drugs. Their aqueous nanosuspensions, produced via wet stirred media milling, were mixed with hydroxypropyl methylcellulose solution containing glycerin as plasticizer, followed by casting and drying to form films. For the purpose of comparison, sodium dodecyl sulfate (SDS) was used as surfactant, but was found to be unnecessary for achieving fast dissolution (t80 between 18 and 28 min) for all five drugs. Interestingly, SDS was required for the full recovery of nanoparticles for PB, yet lack of it did not impact the dissolution. Interactions between drug and polymer were investigated with FTIR spectroscopy whereas drug crystallinity within the film was investigated via Raman spectroscopy. Films for all drugs, even for very small samples, exhibited excellent content uniformity (RSD <4%) regardless of use of surfactant. Overall, these results demonstrate the novelty and robustness of the polymer strip film platform for fast release of poorly water-soluble drugs without requiring any surfactants.

Fast drying of biocompatible polymer films loaded with poorly water-soluble drug nano-particles via low temperature forced convection.

Fast drying of nano-drug particle laden strip-films formed using water-soluble biocompatible polymers via forced convection is investigated in order to form films having uniform drug distribution and fast dissolution. Films were produced by casting and drying a mixture of poorly water soluble griseofulvin (GF) nanosuspensions produced via media milling with aqueous hydroxypropyl methylcellulose (HPMC E15LV) solutions containing glycerin as a plasticizer. The effects of convective drying parameters, temperature and air velocity, and film-precursor viscosity on film properties were investigated. Two major drying regimes, a constant rate period as a function of the drying conditions, followed by a single slower falling rate period, were observed. Films dried in an hour or less without any irreversible aggregation of GF nanoparticles with low residual water content. Near-infrared chemical imaging (NIR-CI) and the content uniformity analysis indicated a better drug particle distribution when higher viscosity film-precursors were used. Powder X-ray diffraction showed that the GF in the films retained crystallinity and the polymorphic form. USP IV dissolution tests showed immediate release (~20 min) of GF. Overall, the films fabricated from polymer-based suspensions at higher viscosity dried at different conditions exhibited similar mechanical properties, improved drug content uniformity, and achieved fast drug dissolution.

Electrodeless electrohydrodynamic drop-on-demand encapsulation of drugs into porous polymer films for fabrication of personalized dosage units.

Noncontact drop-on-demand (DOD) dosing is a promising strategy for manufacturing 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.