Use of telephone and web interfaces of interactive response technology at clinical investigator sites in clinical trials

Background Interactive response technologies are used in clinical trials to provide services such as automated randomization and medication logistics management. The objective of this article is to investigate the usage of telephone (Interactive Voice Response) and web (Interactive Web Response) interfaces of interactive response technologies at clinical investigator sites in clinical trials, to obtain information about the preferences of interactive response technology end users between the telephone and web interfaces, and to explore the relevance of the telephone interface in this setting. Methods The data consist of an online survey conducted in spring 2016 with clinical investigators, study nurses, and pharmacists in 13 countries. Results Ninety-eight percent of survey respondents preferred the web interface over the telephone interface, the most important reason being superior usability. However, the respondents indicated the usability of interactive response technology interfaces is not optimal, and lack of integration and consistency across systems is common. A vast majority of interactive response technology end users at clinical sites prefer to use the web interface over the telephone interface, but most also feel there would need to be a back-up system. Conclusions Based on the results, it would be beneficial to improve the usability of the interactive response technology interfaces, and to increase consistency across systems from the current level. Support to and training of the users, as well as clarifying the responsibilities between sites and the sponsor should also be a focal point. Study sponsors should explore with interactive response technology service providers how removing the telephone interface would impact future studies, and whether there could be a more efficient means to achieve a reliable back-up to the web interface instead of a dedicated telephone interface.Peer reviewe

Comparison between a novel combination of bioactive glass with clodronate and bioactive glass alone as a treatment for chronic periodontitis

Peer reviewe

Effect of colloidal silicon dioxide and moisture on powder flow properties : Predicting in-process performance using image-based analysis

The effect of colloidal silicon dioxide (CSD) on powder flow properties of poor-flowing excipient lactose 200 M was investigated. Binary mixtures of different ratios of CSD as glidant were examined using a modern imagebased flow measuring technique. Special attention was placed to subtle variations in powder flow from small changes in glidant concentration (0.025% w/w). Understanding the modes of interaction of particles and their effects on flowability using the method predicted the die filling performance during tablet manufacture. In addition, the importance of moisture content on powder flow properties was empirically underlined. A more efficient range of CSD was detected from 0.10 to 0.50% w/w in most of the tested conditions, which revealed a significant improvement in powder flow performance compared to higher amounts typically handled in the pharmaceutical industry.Peer reviewe

Image-based characterization of powder flow to predict the success of pharmaceutical minitablet manufacturing

Powder flowability plays an important role in die filling during tablet manufacturing. The present study introduces a novel small-scale measuring technique for powder flow. Based on image analysis, the flow was defined depending on the variation of luminous intensity and the movement of powder inside the measurement cuvette. Using quantities around 100 mg it was possible to characterize a wide range of common pharmaceutical powders, especially in distinguishing subtle differences in flow caused by minor changes in samples characteristics. The method was compared with powder rheometry, which is widely used in the pharmaceutical literature, and showed a significant improvement in predicting the success of pharmaceutical minitablet manufacture (d = 5 mm). Tablet weight variation (RSD) was defined as the most efficient way to assess relevant powder flow behaviour in tablet production when using the novel device. The proposed method was distinguished from others by its ability to classify different grades of microcrystalline cellulose in the die-filling process. Subsequently, eight common pharmaceutical powders, both excipients and APIs, were properly ranked as a function of flowability based on their physical properties. The method showed a high repeatability, with a relative standard deviation not more than 10%.Peer reviewe

Atomic layer deposition-A novel method for the ultrathin coating of minitablets

We introduce atomic layer deposition (ALD) as a novel method for the ultrathin coating (nanolayering) of minitablets. The effects of ALD coating on the tablet characteristics and taste masking were investigated and compared with the established coating method. Minitablets containing bitter tasting denatonium benzoate were coated by ALD using three different TiO2 nanolayer thicknesses (number of deposition cycles). The established coating of minitablets was performed in a laboratory-scale fluidized-bed apparatus using four concentration levels of aqueous Eudragit (R) E coating polymer. The coated minitablets were studied with respect to the surface morphology, taste masking capacity, in vitro disintegration and dissolution, mechanical properties, and uniformity of content. The ALD thin coating resulted in minimal increase in the dimensions and weight of minitablets in comparison to original tablet cores. Surprisingly, ALD coating with TiO2 nanolayers decreased the mechanical strength, and accelerated the in vitro disintegration of minitablets. Unlike previous studies, the studied levels of TiO2 nanolayers on tablets were also inadequate for effective taste masking. In summary, ALD permits a simple and rapid method for the ultrathin coating (nanolayering) of minitablets, and provides nanoscale-range TiO2 coatings on porous minitablets. More research, however, is needed to clarify its potential in tablet taste masking applications. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Evaluation of new flavors for feline mini-tablet formulations

Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still lacking in palatable and voluntarily acceptable drugs of suitable size and attractive taste. As a consequence, treating cats with canine or human medicinal products has weakened patient compliance and treatment commitment resulting in many pet cats going untreated. In the future, the companion animal pharmaceutical business is expected to focus particularly on cats and the development of palatable feline medication. Based on this, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically the aim was to develop sophisticated and tailor-made feline medicinal products, in the form of mini-tablets, focusing on flavors palatable to felines. Rapid preformulation compatibility and stability screening tests of synthetic flavors were carried out using readily available oral solid form excipients. On the basis that felines are carnivorous, Lmethionine, L-leucine, L-proline and thiamine hydrochloride were investigated as possible flavors for improving palatability. These flavors, together with a model substance for a bitter taste, denatonium benzoate, were evaluated for their physicochemical properties, stability and physical compatibility. This evaluation was carried out with the substances alone and in binary combinations of flavors and excipients. Stability and compatibility were examined using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The results showed that L-proline and denatonium benzoate anhydrate were hygroscopic. Thiamine hydrochloride was incompatible with talc and sodium stearyl fumarate. The known incompatibility between the amines contained in flavors, and α-lactose monohydrate was used to assess method sensitivity. Overall, this study provided new information on the compatibility of novel flavors with oral solid form excipients. This study also showed the applicability of using XRPD and DSC for the rapid evaluation of instability and incompatibility

Evaluation of new aroma substances for feline minitablet formulation

Despite the global interest in companion animal pharmaceuticals, feline peroral medication still lacks tailor-made, palatable and voluntarily accepted pharmaceuticals with suitable size and attractive taste. As a consequence, treating cats with canine and even human pharmaceuticals has weakened patient compliance and treatment commitment, and has even left many pet cats untreated. In future, the companion animal pharmaceutical business will therefore particularly concentrate on cats and the rapid and economic development of palatable feline medication. Following this goal, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically we aimed to develop sophisticated and tailor-made feline pharmaceuticals, with the focus on flavours in minitablets. Since excipients should be easily obtained and suitable for formulation, we conducted rapid preformulation compatibility and stability screening tests of synthetic flavours with commonly used tableting excipients. On the basis of the feline carnivorous diet, L-methionine, L-leucine, L-proline and thiamine hydrochloride were presented as new aroma substances for the improvement of feline medication palatability. These flavours and a model substance for a bitter taste, denatonium benzoate, were systematically evaluated for their physicochemical properties, stability and physical compatibility. This was done with substances alone and in binary combinations of flavours and excipients. Stability and compatibility were examined employing DSC and XRPD. The results showed that L-proline and denatonium benzoate anhydrate were hygroscopic. Thiamine hydrochloride was incompatible with talc and sodium stearyl fumarate. The known incompatibility between the amines contained in aromas, and α-lactose monohydrate was used in assessing method sensitivity. Overall, the study provided new information on the compatibility of novel aromas with the tableting excipients. The study also demonstrated the applicability of XRPD and DSC in the rapid evaluation of instability and incompatibility

Time-Gated Raman Spectroscopy for Quantitative Determination of Solid-State Forms of Fluorescent Pharmaceuticals

Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 X (2) X 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.Peer reviewe