The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban

Direct compression represents a favorable tablet manufacturing method. However, obtaining satisfactory mechanical properties of the compacts and drug dissolution remains a challenge in formulation development, particularly in the case of challenging model drugs. Rivaroxaban is classified as a class II model drug according to the Biopharmaceutical Classification System and exhibits prominent cohesiveness and low aqueous solubility (Choi et al., 2022). The aim of this work was to evaluate the influence of different directly compressible fillers/diluents on selected compact properties (namely, tensile strength, friability, and disintegration) and the dissolution of rivaroxaban from the prepared compacts.14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia, 202

ORBIS (Open Research Biopharmaceutical Internships Support) – Building Bridges Between Academia and Pharmaceutical Industry to Improve Drug Development

Peer reviewe

Encapsulation of fluorogenic probes and pharmacologically active molecules into nanoparticles for enhancing cellular uptake

Les nanoparticules polymériques présentent la capacité d améliorer le transport et le ciblage des médicaments vers un site d'action défini mais également la capacité de transporter des substances actives peu solubles, faiblement absorbées ou fragiles. Dans ce travail, deux types de substances actives ont été encapsulées au sein de nanoparticules: d une part des sondes fluorogéniques pour le ciblage du glutathion réduit (GSH) intracellulaire, à savoir l'ortho-phthaldialdehyde (OPA) et le naphtalène-2,3-dicarboxaldehyde (NDA), et d autre part la calcitonine de saumon (sCT) qui est une hormone polypeptidique. Les nanoparticules d OPA ou de NDA ainsi que des nanoparticules de sCT ont été préparées respectivement à l aide de techniques de simple ou de double émulsion avec évaporation du solvant. Les nanoparticules obtenues ont été caractérisées en terme de taille, potentiel zêta, taux d encapsulation, libération in vitro du principe actif, cytotoxicité, morphologie ou encore au niveau de leurs propriétés thermiques. Les nanoparticules chargées de NDA ont été incubées en présence de levures et la concentration en adduit NDA-GSH intracellulaire était augmentée environ 9 fois par rapport à la concentration en adduits formés à partir de la sonde libre. Dans le cas de la sCT, l'étude in vivo menée chez des rats a démontré que, après une injection sous-cutanée de nanoparticules, les taux sériques élevés obtenus pouvaient être maintenus pendant 3 jours. En conclusion, les substances actives incorporées au sein des nanoparticules ont permis une meilleure pénétration cellulaire du NDA et une meilleure biodisponibilité de la sCT par rapport à ces mêmes molécules non encapsulées.Polymeric nanoparticles have been considered to have the potential to improve drug delivery to the desired site of action and to enable delivery of poorly soluble, poorly absorbed or unstable drugs. In this work, two types of active substances have been chosen for encapsulation in polymeric nanoparticles: fluorogenic probes for intracellular targeting of the reduced glutathione (GSH), namely ortho-phthaldialdehyde (OPA) and naphthalene-2,3-dicarboxaldehyde (NDA), as well as salmon calcitonin (sCT) which is a polypeptide hormone. The probe or sCT-loaded nanoparticles were obtained using a simple or double emulsion solvent evaporation method, respectively. The obtained nanoparticles were thoroughly characterized, e.g. in terms of the size, zeta potential, encapsulation efficiency, drug (probe) release, cytotoxicity or microscopic morphology and thermal properties. NDA-loaded nanoparticles were incubated with yeast cells and intracellular NDA-GSH adduct levels increased by about 9-times in comparison with the free probe. In the case of sCT, the in vivo study was conducted in rats, and it was demonstrated that after subcutaneous injection of sCT-loaded nanoparticles, elevated serum sCT levels could be sustained for 3 days. In conclusion, the active molecules incorporated in polymeric nanoparticles achieved the better cellular uptake (NDA) and bioavailability (sCT) that the non encapsulated ones.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form

Physical Ageing of Amorphous Poly(lactic acid)-Indapamide System Studied by Differential Scanning Calorimetry

The process of isothermal and non-isothermal physical ageing of amorphous polylactide (PLA) with the active pharmaceutical ingredient, indapamide (IND), was investigated. A PLA–IND system with a 50/50 weight ratio was obtained and characterized using differential scanning calorimetry (DSC). In the 50/50 (w/w) mixture, two glass transitions were observed: the first at 64.1 ± 0.3 °C corresponding to the glass transition temperature (Tg) of PLA, and the second at 102.6 ± 1.1 °C corresponding to the Tg of IND, indicating a lack of molecular mixing between the two ingredients. The PLA–IND system was subjected to the isothermal physical ageing process at different ageing temperatures (Ta) for 2 h. It was observed that the highest effect of physical ageing (enthalpy relaxation change) on IND in the PLA–IND system occurred at Ta = 85 °C. Furthermore, the system was annealed for various ageing times at 85 °C. The relaxation enthalpies were estimated for each experiment and fitted to the Kohlrausch–Williams–Watts (KWW) equation. The KWW equation allowed for the estimation of the relaxation time and the parameter describing the distribution of relaxation times of the isothermal physical ageing process of IND in the PLA–IND system. The physical ageing of the PLA–IND mixture (50/50) was also discussed in the context of heat capacity. Moreover, the activation energy and fragility parameters were determined for the PLA–IND (50/50) system

From visible to white-light emission by siloxane-capped ZnO quantum dots upon interaction with thiols

International audienceThe interaction of thiols (glutathione, cysteine, and cysteamine) with yellow-emitting siloxane-capped ZnO QDs was studied. A gradual enlargement of the PL emission band resulting in white-light emission was observed upon reaction with thiols, while the diameter (ca. 4 nm) and the crystallinity of the dots were not affected. The appearance of broad white-emission was accompanied by a decrease of the photoluminescence quantum yield from 16% to 5-6%. Generation of surface defect states through interaction of the thiols with Zn surface atoms of the dots provoking shrunk of the siloxane capping may be responsible of that broadband emission throughout most of the light spectrum

Phototoxic or Photoprotective?—Advances and Limitations of Titanium (IV) Oxide in Dermal Formulations—A Review

The widespread role of titanium (IV) oxide (TiO2) in many industries makes this substance of broad scientific interest. TiO2 can act as both a photoprotector and photocatalyst, and the potential for its role in both applications increases when present in nanometer-sized crystals. Its sunlight-scattering properties are used extensively in sunscreens. Furthermore, attempts have been made to incorporate TiO2 into dermal formulations of photolabile drugs. However, the propensity to generate reactive oxygen species (ROS) rendering this material potentially cytotoxic limits its role. Therefore, modifications of TiO2 nanoparticles (e.g., its polymorphic form, size, shape, and surface modifications) are used in an effort to reduce its photocatalytic effects. This review provides an overview of the potential risks arising from and opportunities presented by the use of TiO2 in skin care formulations

Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets – a case study

<p>The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett–Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.</p