[Pharmaceutical Properties of Anti-inflammatory Analgesic Patches Using Acrylic Polymer].

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.

Measurement of the Water Content in Semi-solid Formulations Used to Treat Pressure Ulcers and Evaluation of Their Water Absorption Characteristics.

We investigated the water contents in commercial semi-solid preparations used for pressure ulcer (PU) treatment using near-IR spectroscopy (NIRS) and compared the results with those measured using the Karl Fischer (KF) method. The aim of this study was to determine a standard method and select the appropriate topical preparation with the optimal moisture for PU treatment. The water absorption properties of bases and formulations were evaluated with a time-dependent factor using Transwell as the model membrane. KF and NIRS were applicable as measurement methods of the water content in semi-solid formulations. NIRS was shown to be a useful, simple, nondestructive tool that is more advantageous than the KF method. The water absorption characteristics tested using Transwell revealed that the rate of and capacity for water absorption are determined not only by the absorption ability of the polymer base but also by other factors, such as the osmotic pressure exerted by additives. KF and NIR measurements can be used to choose external skin preparations to control the amount of water in PU treatment.

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer.

Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm-1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.