Influence of Testing Parameters on In Vitro Tramadol Release from Poloxamer Thermogels using the Immersion Cell Method.

The immersion cell is an in vitro performance test of drug release from semisolids. Several studies made use of immersion cells to investigate drug release from thermosensitive Poloxamer-based gels; however, specifications on the parameter setting are not yet available. Therefore, the aim of this study was to evaluate the influence of testing parameters on tramadol (a model drug) release, release rate, and dissolution efficiency (DE) from Poloxamer gels, using immersion cells. The thermosensitive gelling formulation showed batch-to-batch uniformity of gelling behavior, drug content, and drug release. The use of a membrane in the immersion cell resulted in slower drug release as compared to the absence of a membrane. Moreover, the faster the paddle rotation, the faster the drug release was. Membrane thickness showed a strong and significant linear relationship with corresponding DE values (Pearson's correlation coefficient, r = -0.9470; p = 0.004). Factors that did not influence drug release include paddle position, i.e., distance between paddle and membrane, as well as membrane mean pore size. This study sets forth the importance of carefully controlling the following parameters including presence/absence of membrane, paddle rotation speed, and membrane thickness during the setup of release experiments from gels using immersion cells.

Could albumin affect the self-assembling properties of a block co-polymer system and drug release? An in-vitro study.

PURPOSE: This work investigated the influence of a model protein, bovine serum albumin (BSA), on the properties of a thermogelling formulation intended for administration inside body compartments where there is high albumin content, as in the case of inflamed joints; it also explored the relation between the variation of these properties and release performance of methotrexate (MTX), a drug used to treat forms of arthritis and rheumatic conditions. METHODS: The influence of BSA on the micellisation and gelation behaviour of Poloxamer 407, chosen as a model copolymer, was studied by differential scanning calorimetry (microDSC), dynamic light scattering (DLS), fluorescence spectroscopy and rheology studies. A release study of MTX loaded inside the hydrogel in presence and in absence of BSA was performed. RESULTS: DLS and microDSC data revealed that the micellisation process was not affected by the protein, as demonstrated by unaltered micellar size and thermodynamic parameters. While the presence of BSA in the copolymer system reduced gel consistency, the hydrogel release performance was only slightly affected. CONCLUSION: Our results suggested that the kinetics of MTX release mainly depended on the presence of the thermogelling copolymer, although other mechanisms related to BSA could be involved. Finally, the study assessed the feasibility of using a thermogelling hydrogel for in situ drug administration in areas with the presence of high protein concentrations.

Advancing the understanding of the tablet disintegration phenomenon - An update on recent studies.

Disintegration is the de-aggregation of particles within tablets upon exposure to aqueous fluids. Being an essential step in the bioavailability cascade, disintegration is a fundamental quality attribute of immediate release tablets. Although the disintegration phenomenon has been studied for over six decades, some gaps of knowledge and research questions still exist. Three reviews, published in 2015, 2016 and 2017, have discussed the literature relative to tablet disintegration and summarised the understanding of this topic. Yet, since then more studies have been published, adding to the established body of knowledge. This article guides a step forward towards the comprehension of disintegration by reviewing, concisely, the most recent scientific updates on this topic. Initially, we revisit the mechanisms of disintegration with relation to the three most used superdisintegrants, namely sodium starch glycolate, croscarmellose sodium and crospovidone. Then, the influence of formulation, storage, manufacturing and media conditions on disintegration is analysed. This is followed by an excursus on novel disintegrants. Finally, we highlight unanswered research questions and envision future research venues in the field.

Rheological properties of cellulosic thickeners in hydro-alcoholic media: The science behind the formulation of hand sanitizer gels.

Cellulosic-based thickeners are commonly used in the preparation of hydro-alcoholic hand sanitisers. Yet, little is known about the behaviour of these polymeric dispersions in hydro-alcoholic mixtures. Here, we studied the dispersion ability and rheology of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and sodium carboxymethyl cellulose in water-ethanol mixtures. Hydroxypropyl cellulose formed transparent dispersions across the entire range of ethanol concentrations, while a critical ethanol concentration (CEC), above which dispersions became turbid, was found for all the other polymers. At and below the CEC, all the rheological parameters followed a bell-like shape profile as a function of ethanol concentration. Moreover, the molecular weight and degree of substitution of the polymers influenced the rheological properties. The CEC and rheological behaviour of the dispersions were both dependent on the ethanol/polymer and water/polymer interactions. As hand disinfectants should contain 60-95% ethanol, polymers of higher CEC, such as hydroxypropyl cellulose and hydroxypropyl methylcellulose, are recommended.

Heating treatments affect the thermal behaviour of doxorubicin loaded in PEGylated liposomes.

Doxil® is a stealth marketed PEGylated liposomal formulation, containing the anticancer drug doxorubicin. After loading via a pH gradient, fibrillar supramolecular structures of doxorubicin sulfate originates inside the core of the liposomes. Recently, the crystallinity of doxorubicin sulfate has been confirmed by high-resolution calorimetry. However, no detailed information are available on the nature of doxorubicin sulfate nanocrystals and on the effect of different thermal treatments. Thus, the aim of this work was to characterize the thermal behaviour of Doxil® in comparison to the unloaded liposomes using microcalorimetry, dynamic light scattering and high-resolution ultrasound spectroscopy (HR-US). Different thermal programmes were applied with the aim to highlight the effect of the treatments on the formulation. The used techniques confirmed the ordered state of doxorubicin nanocrystals inside PEGylated liposomes. Particularly, microcalorimetry and HR-US highlighted the changes in the thermal behaviour of the drug under different heating programmes. Doxorubicin nanocrystals were found to be stable after heating up to 80°C, but an irreversible thermal behaviour was observed after a prolonged heating at elevated temperature (2h at 80°C). The non-reversibility could be related to the formation of a different ordered structure and enhanced by the slight leakage of the drug occurring after a prolonged heating.

Water-in-Oil Microemulsions for Protein Delivery: Loading Optimization and Stability.

BACKGROUND: Microemulsions are attractive delivery systems for therapeutic proteins and peptides due to their ability to enhance bioavailability. Although different proteins and peptides have been successfully delivered through such ternary systems, no information can be found about protein loading and the formulation stability when such microemulsions are prepared with pharmaceuticallyapproved oils and surfactants. The aim of this work was to optimise a ternary system consisting of water/ ethyl oleate/Span® 80-Tween® 80 and to determine its protein loading capacity and stability, using bovine serum albumin (BSA) as a model of biomolecule. METHODS: The optimization was carried out using a Central Composite Design and all the prepared formulations were characterised through dynamic light scattering, rheology, optical and polarized microscopy. Subsequently, the maximum loading capacity was determined and the stability of the final microemulsion with the highest content of protein was followed over six months. To investigate the structural features of the protein, BSA was recovered from the microemulsion and analysed through fluorescence spectroscopy. RESULTS: After incorporation of the protein in the microemulsion, a decrease of its aqueous solubility was observed. However, the formulation remained stable over six months and the native-like state of the recovered protein was demonstrated by fluorescence spectroscopy Conclusion: This study demonstrated the feasibility of preparing microemulsions with the highest content of protein and their long-term stability.