Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying.

A co-amorphous model drug was prepared by the spray-drying (SD) of probucol (PC) and atorvastatin calcium trihydrate salt (ATO) as low water solubility and co-former components, respectively. The physicochemical properties of the prepared samples were characterized by powder X-ray diffraction (PXRD) analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and dissolution tests. Stability tests were also conducted under a stress environment of 40 °C and 75% relative humidity. The results of PXRD measurements and thermal analysis suggested that PC and ATO form a co-amorphous system by SD. Thermal analysis also indicated an endothermic peak that followed an exotherm in amorphous PC and a physical mixture (PM) of amorphous PC and ATO; however, no endothermic peak was detected in the co-amorphous system. The dissolution profiles for PC in the co-amorphous sample composed of PC and ATO were improved compared to those for raw PC crystals or the PM. Stability tests indicated that the co-amorphous material formed by PC and ATO can be stored for 35 d without crystallization, whereas amorphous PC became crystallized within a day. Therefore, co-amorphization of PC and ATO prepared by SD is considered to be a useful method to improve the solubility of PC in water.

[Microtaggant Technology for Ensuring Traceability of Pharmaceutical Formulations: Potential for Anti-counterfeiting Measures, Distribution and Medication Management].

The globalization of drug trade has led to the increased production of falsified medicines. In addition, poor medication adherence increases the costs of healthcare. The need to manage medication has given rise to marketing of highly functional networked digital medicine. Therefore, a growing need has emerged to ensure the traceability of pharmaceutical products from shipment to patient distribution. Microtaggant technologies that can encode individual numbers on pharmaceutical products are expected to serve achieving this goal. Taggants are a class of materials that can be applied to an object to make it identifiable, like barcodes and holograms. Since the smaller size of microtaggant make it invisible to naked eyes, it is more difficult to reverse-engineer than conventional taggants. The U.S. Food and Drug Administration (FDA) has established guidelines for the use of microtaggants. Many studies have explored the use of various analytical technologies and materials as the microtaggants. However, the advantages and disadvantages of each method have not been established yet. In this review, recent research on the use of microtaggants for anti-counterfeiting is summarized and compared to current anti-counterfeiting technologies with spectrographic methods, distribution management systems with barcodes, and medication management systems with sensor devices. We also discuss the microtaggants implementation costs and security level.

Physical stability of stealth nanobeacon using surface-enhanced Raman scattering for anti-counterfeiting and monitoring medication adherence: Deposition on various coating tablets.

Microtaggant technologies can encode individual numbers on coating tablet to authenticate pharmaceutical products and, therefore, combat the global spread of falsified medicine. In this study, a novel microtaggant, stealth nanobeacon (NB), with surface-enhanced Raman scattering (SERS) activity was applied to various coating tablets and its physical stability was evaluated. The NBs were composed of a reporter molecule (AH, adenine hydrochloride) and prepared with different sizes of gold nanoparticles (AuNPs). The NBs were directly deposited on the surface of various model coatings (e.g., hydroxypropyl cellulose, hydroxypropyl methyl cellulose, Eudragit® RS30D, ethyl cellulose). To investigate physical stability of the NB on the coating tablets, SERS spectra of the NB after friability test and acceleration test (store at 75% RH, 40 °C) were evaluated using a portable Raman spectrometer. After the friability test, there was no significant decrease in the peak intensity of the SERS signal (PH) for authentication in all samples. In the acceleration test, the SERS signals of the samples were attenuated, but sufficient SERS signal intensity (PH > 70) was maintained in the seven types of coating for authentication. These results demonstrate that the microtaggant NB has the potential to be used for a wide range of coating tablets.

Physically unclonable functions taggant for universal steganographic prints.

Counterfeiting of financial cards and marketable securities is a major social problem globally. Electronic identification and image recognition are common anti-counterfeiting techniques, yet they can be overcome by understanding the corresponding algorithms and analysis methods. The present work describes a physically unclonable functions taggant, in an aqueous-soluble ink, based on surface-enhanced Raman scattering of discrete self-assemblies of Au nanoparticles. Using this stealth nanobeacon, we detected a fingerprint-type Raman spectroscopy signal that we clearly identified even on a business card with a pigment mask such as copper-phthalocyanine printed on it. Accordingly, we have overcome the reverse engineering problem that is otherwise inherent to analogous anti-counterfeiting techniques. One can readily tailor the ink to various information needs and application requirements. Our stealth nanobeacon printing will be particularly useful for steganography and provide a sensitive fingerprint for anti-counterfeiting.

Design and preparation of nanocomposite acrylate coating agents for binder-free dry coating of 100 µm-sized drug-containing particles and their coating performance.

For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process.

Crystallographic evaluation of the conformation of quetiapine included in ß-cyclodextrin.

Single-crystal X-ray diffraction and theoretical calculations were conducted for insights into the ß-cyclodextrin (ß-CD)-quetiapine inclusion complex structure. ß-CD and quetiapine form a host-guest inclusion complex at a ratio of 2:1 in which the ß-CD molecules form head-to-head dimers with their secondary hydroxyl groups linked by multiple hydrogen bonds. Quetiapine is totally contained within the ß-CD cavity and exhibits two kinds of disorder (parts 1 and 2) in opposite directions in the ß-CD complex. To clarify the mobility of the guest molecule in the ß-CD cavity, theoretical molecular conformational calculations, crystal optimization and crystal energy calculations were conducted using CONFLEX software. The results of theoretical molecular conformation calculations showed that the mobility of quetiapine is restricted because its tricyclic structure is covered by ß-CD. The results of crystal energy calculations indicated that the conformation of disorder part 1, which has high occupancy, was more stable.

Binder-free dry particulate coating process using a mild vibration field: Effects of glass-transition temperature and powdering method of polymeric coating agents on coating performance.

We employed a new dry coating process with mild-intensity vibration to prepare a 100-µm-sized microparticle capable of prolonged release of a drug. To accomplish this without using a binder, a series of laboratory-made acrylic latexes with different glass transition temperatures (Tg) ranging from 30 °C to 80 °C were employed as coating agents, and the effects of Tg and powdering method of the coating agents on coating performance were investigated. The laboratory-made acrylic latexes were powdered by spray-drying (SD) or freeze-drying (FD). Diclofenac sodium (DS)-loaded ion-exchange-resin with particle size ∼100 µm was used as a core particle. The process utilized vibrations with amplitude of 0.5 mm and frequency of 90 Hz to form an ordered mixture composed of the core particles with the loosely-layered coating agents. Subsequently, the coating agents were fixed mechanically on the core particle by impaction of zirconia beads. The coating agents powdered by FD showed higher coating efficiencies than those powdered by SD, irrespective of the differences in Tg values. Among the coating agents powdered by FD, the particles coated at Tg = 60 °C exhibited the most prolonged drug-release, although the coating efficiency was not the highest. In our proposed process utilizing mild vibration, we demonstrated that adjusting the Tg of the coating agents is crucial to the formation of binder-free multiple coating layers for prolonged drug release.