Challenges and opportunities to include patient-centric product design in industrial medicines development to improve therapeutic goals.

In the past, drug developers in industry chose approaches mainly focusing on the drug product's efficacy, safety and quality according to the level required by regulatory expectations stipulated in guidelines, pharmacopoeia and other regulatory provisions. By putting more focus on the patient perspective, regulatory authorities are currently raising their requirements regarding successful product submissions. The increasing involvement of patients in the product development process (e.g. conduction of human factor use tests, integration of feedback from patient and patient advisory groups into clinical programmes) requires adaptations to the existing and established industrial drug development processes without compromising fast patient access to innovative therapies. This review provides an expert opinion on the emerging challenges and opportunities to implement a patient-centric approach into new drug development programmes. The aim is to better understand the challenge of finding the right balance between bringing innovative drugs fast to the patients and to develop these in parallel in a patient-centric product form as well as why this is an opportunity and how stakeholder parties (e.g. patients, clinicians, pharmacists, caregivers, regulators) can provide support to achieve desired outcomes.

Swelling, Mechanics, and Thermal/Chemical Stability of Hydrogels Containing Phenylboronic Acid Side Chains.

We report here studies of swelling, mechanics, and thermal stability of hydrogels consisting of 20 mol % methacrylamidophenylboronic acid (MPBA) and 80 mol % acrylamide (AAm), lightly crosslinked with methylenebisacrylamide (Bis). Swelling was measured in solutions of fixed ionic strength, but with varying pH values and fructose concentrations. Mechanics was studied by compression and hold. In the absence of sugar or in the presence of fructose, the modulus was mostly maintained during the hold period, while a significant stress relaxation was seen in the presence of glucose, consistent with reversible, dynamic crosslinks provided by glucose, but not fructose. Thermal stability was determined by incubating hydrogels at pH 7.4 at room temperature, and 37, 50, and 65 °C, and monitoring swelling. In PBS (phosphate buffered saline) solutions containing 9 mM fructose, swelling remained essentially complete for 50 days at room temperature, but decreased substantially with time at the higher temperatures, with accelerated reduction of swelling with increasing temperature. Controls indicated that over long time periods, both the MPBA and AAm units were experiencing conversion to different species.

Improved physical stability of amorphous state through acid base interactions.

To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically.

Introduction of pH-Sensitivity into Mechanically Strong Nanoclay Composite Hydrogels Based on N-Isopropylacrylamide.

pH-sensitive nanoclay composite hydrogels based on N-isopropylacrylamide (NIPA) were synthesized by copolymerization with cationic and anionic comonomers. Laponite nanoclay particles served as multifunctional crosslinkers, producing hydrogels with exceptionally high mechanical strengths, as measured by elongation at break. Cationic copolymer gels based on NIPA and dimethylaminoethylmethacrylate were prepared by aqueous free radical polymerization, adopting a procedure reported by Haraguchi (Adv Mater 2002, 14, 1120-1124). Without modification, this technique failed to produce anionic copolymer gels of NIPA and methacrylic acid due to flocculation of clay particles. Three methods were conceived to incorporate acidic MAA into nanoclay hydrogels. First, NIPA was copolymerized with acidic comonomer under dilute conditions, producing hydrogels with good pH-sensitivity but weak mechanical characteristics. Second, NIPA was copolymerized with methyl methacrylate, which was then hydrolyzed to generate acid sidegroups, yielding hydrogels that were much stronger but less pH sensitive. Third, NIPA was copolymerized with an acid comonomer following modification of the nanoclay surface with pyrophosphate ions. The resulting hydrogels exhibited both strong pH-sensitivities at 37 degrees C and excellent tensile properties. Optical transparency changed during polymerization, depending on hydrophobicity of the components. This work increases the diversity and functionality of nanoclay hydrogels, which display certain mechanical advantages over conventionally crosslinked hydrogels.