Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets

Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth. The results showed that the newly developed Aston test was able to differentiate between different ODTs with small disintegration time windows, as well as between immediate release tablets and ODTs. The Aston test provided higher correlations between ODT properties and disintegration time compared to the USP test method and most significantly, resulted in a linear in vitro/in vivo correlation (IVIVC) (R 2 value of 0.98) compared with a "hockey stick" profile of the USP test. This study therefore concluded that the newly developed Aston test is an accurate, repeatable, relevant and robust test method for assessing ODT disintegration time which will provide the pharmaceutical industry and regulatory authorities across the world with a pragmatic ODT testing regime

Effect of Cyclodextrin Complexation on the Aqueous Solubility and Solubility/Dose Ratio of Praziquantel

Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound like PZQ could behave as BCS-Class I (highly soluble/highly permeable) drug. Phase solubility and the kneading and lyophilization techniques were used for inclusion complex preparation; solubility was determined by UV spectroscopy. The ability of the water soluble polymer polyvinylpyrolidone (PVP) to increase the complexation and solubilization efficiency of β-CD and HP-β-CD for PZQ was examined. Results showed significant improvement of PZQ solubility in the presence of both cyclodextrins but no additional effect in the presence of PVP. The solubility/dose ratios values of PZQ-cyclodextrin complexes calculated considering the low (150 mg) and the high dose (600 mg) of PZQ, used in practice, indicate that PZQ complexation with CDs may result in drug dosage forms that would behave as a BCS-Class I depending on the administered dose

A Rapid Method for the Separation of Functional Lymphoid Cell Populations of Human and Animal Origin on PVP-Silica (Percoll) Density Gradients

Subclasses of lymphocytes can be separated on gradients of non-toxic polyvinylpyrrolidone-coated colloidal silica (Percoll) by virtue of differential densities. Such gradients can yield functionally active lymphocyte populations after brief centrifugation. Gradients can be generated in a discontinuous step fashion and centrifuged in standard table-top laboratory centrifuges or as self-generating gradients during ultracentrifugation. The density medium has low viscosity and can be made isotonic for virtually any use. Gradients have proved useful in both human and experimental animal studies, and high percentage yields allow for separations from small cell numbers. Methods are described for separation of whole blood and lymphoid subpopuctions. The cytoxic capability of various density fractions was evaluated for mixed lymphocyte culture-induced allogeneic killing and spontaneous, so-called "natural" killer cell activity. The lower density associated with blast transformation allows for significant enrichments of stimulated cells from in vitro cultures. Higher thymidine incorporation, restimualtion in mixed lymphocyte reactions, and greater cytotoxic capacity are associated with these "blast" fractions

Ecological Indicators of Ecosystem Recovery : Microbial Communities as Ecological Indicators of Ecosystem Recovery Following Chemical Pollution

National audience‘Ecosystem recovery’ is a concept that emerged from the need to preserve our environment against increasing contamination from human activity. However, ecological indicators of ecosystem recovery remain scarce, and it is still difficult to assess recovery of ecological processes at relevant spatial and temporal scales. Microbial communities hold key relevance as indicators of ecosystem recovery as they are ubiquitous among diverse ecosystems, respond rapidly to environmental changes, and support many ecosystem functions and services through taxonomic and functional biodiversity. This chapter summarizes the state-of-the-art in knowledge on the processes driving the structural and functional recovery of phototroph and heterotroph microorganisms following chemical pollution. It covers several successful case studies providing proof of principle for the relevance of using microorganisms in recovery studies in various ecosystems such as soil, freshwater and seawater. Questions remain for microbial ecotoxicologists to fully understand and predict how structural and functional recovery observed at microbial scale can reflect the recovery of an ecosystem. Moreover, new standards and norms taking into account recent advances in microbial ecotoxicology are now necessary in order to inform legislators and policymakers on the importance of considering microorganisms in environmental risk assessment, including ecological recovery monitoring

Temperature-responsive properties and drug solubilization capacity of amphiphilic copolymers based on N-vinylpyrrolidone and vinyl propyl ether

A series of amphiphilic copolymers were synthesized by free-radical copolymerization of N-vinylpyrrolidone (NVP) with vinyl propyl ether (VPE), and the structure of the copolymers was characterized by elemental analysis and gel permeation chromatography. The reactivity of VPE in copolymerization was found to be significantly lower than the reactivity of NVP, which resulted in a decrease of copolymers’ yields and molecular weights with higher content of VPE in the feed mixture. An investigation of the behavior of the copolymers in aqueous solutions at different temperatures by dynamic light scattering revealed the presence of lower critical solution temperature, which depending on the content of VPE ranged within 23−38 °C. Aqueous solutions of these copolymers were studied by fluorescent spectroscopy with pyrene as a polarity probe to reveal the formation of hydrophobic domains. The copolymers were found to be useful for enhancing the solubility of riboflavin in water