Practical guidelines for the characterization and quality control of pure drug nanoparticles and nano-cocrystals in the pharmaceutical industry

The number of poorly soluble drug candidates is increasing, and this is also seen in the research interest towards drug nanoparticles and (nano-)cocrystals; improved solubility is the most important application of these nanosystems. In order to confirm the functionality of these nanoparticles throughout their lifecycle, repeatability of the formulation processes, functional performance of the formed systems in pre-determined way and system stability, a thorough physicochemical understanding with the aid of necessary analytical techniques is needed. Even very minor deviations in for example particle size or size deviation in nanoscale can alter the product bioavailability, and the effect is even more dramatic with the smallest particle size fractions. Also, small particle size sets special requirements for the analytical techniques. In this review most important physicochemical properties of drug nanocrystals and nano-cocrystals are presented, suitable analytical techniques, their pros and cons, are described with the extra input on practical point of view.Peer reviewe

3D Printing of Drug Nanocrystals for Film Formulations

The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations

Drug nanocrystals - versatile option for formulation of poorly soluble materials

Poor solubility of drug compounds is a great issue in drug industry today and decreasing particle size is one efficient and simple way to overcome this challenge. Drug nanocrystals are solid nanosized drug particles, which are covered by a stabilizer layer. In nanoscale many physical properties, like compound solubility, are different from the solubility of bulk material, and due to this drug nanocrystals can reach supersaturation as compared to thermodynamic solubility. The most important effect of the smaller particle size is that dissolution rate is highly enhanced mainly due to the increased surface area. In this review the most important properties of nanocrystalline drug compounds are presented, with multiple examples of the development and characterization of nanocrystalline drug formulations.Peer reviewe

3D Printing of Drug Nanocrystals for Film Formulations

The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations

Degrees of order : A comparison of nanocrystal and amorphous solids for poorly soluble drugs

Poor aqueous solubility is currently a prevalent issue in the development of small molecule pharmaceuticals. Several methods are possible for improving the solubility, dissolution rate and bioavailability of Biopharmaceutics Classification System (BCS) class II and class IV drugs. Two solid state approaches, which rely on reductions in order, and can theoretically be applied to all molecules without any specific chemical prerequisites (compared with e.g. ionizable or co-former groups, or sufficient lipophilicity), are the use of the amorphous form and nanocrystals. Research involving these two approaches is relatively extensive and commercial products are now available based on these technologies. Nevertheless, their formulation remains more challenging than with conventional dosage forms. This article describes these two technologies from both theoretical and practical perspectives by briefly discussing the physicochemical backgrounds behind these approaches, as well as the resulting practical implications, both positive and negative. Case studies demonstrating the benefits and challenges of these two techniques are presented.Peer reviewe

Ultrasonic Processing Technique as a Green Preparation Approach for Diacerein-Loaded Niosomes

In this study, the feasibility of ultrasonic processing (UP) technique as green preparation method for production of poorly soluble model drug substance, diacerein, loaded niosomes was demonstrated. Also, the effects of different surfactant systems on niosomes' characteristics were analyzed. Niosomes were prepared using both the green UP technique and traditional thin-film hydration (TFH) technique, which requires the use of environmentally hazardous organic solvents. The studied surfactant systems were Span 20, Pluronic L64, and their mixture (Span 20 and Pluronic L64). Both the production techniques produced well-defined spherical vesicles, but the UP technique produced smaller and more monodisperse niosomes than TFH. The entrapment efficiencies with the UP method were lower than with TFH, but still at a feasible level. All the niosomal formulations released diacerein faster than pure drug, and the drug release rates from the niosomes produced by the UP method were higher than those from the TFH-produced niosomes. With UP technique, the optimum process conditions for small niosomal products with low PDI values and high entrapment efficiencies were obtained when 70% amplitude and 45-min sonication time were used. The overall results demonstrated the potency of UP technique as an alternative fast, cost-effective, and green preparation approach for production of niosomes, which can be utilized as drug carrier systems for poorly soluble drug materials.Peer reviewe

Understanding critical quality attributes for nanocrystals from preparation to delivery

Peer reviewe

Data on characterizing the gene expression patterns of neuronal ceroid lipofuscinosis genes: CLN1, CLN2, CLN3, CLN5 and their association to interneuron and neurotransmission markers: Parvalbumin and Somatostatin

Abstract The article contains raw and analyzed data related to the research article “Neuronal ceroid lipofuscinosis genes, CLN2, CLN3, CLN5 are spatially and temporally co-expressed in a developing mouse brain” (Fabritius et al., 2014) [1]. The processed data gives an understanding of the development of the cell types that are mostly affected by defective function of CLN proteins, timing of expression of CLN1, CLN2, CLN3 and CLN5 genes in a murine model. The data shows relationship between the expression pattern of these genes during neural development. Immunohistochemistry was used to identify known interneuronal markers for neurotransmission and cell proliferation: parvalbumin, somatostatin subpopulations of interneurons. Non-radioactive in-situ hybridization detected CLN5 mRNA in the hippocampus. Throughout the development strong expression of CLN genes were identified in the germinal epithelium and in ventricle regions, cortex, hippocampus, and cerebellum. This provides supportive evidence that CLN1, CLN2, CLN3 and CLN5 genes may be involved in synaptic pruning.Peer reviewe

Effectiveness of psychosocial intervention enhancing resilience among war-affected children and the moderating role of family factors

The study examines, first, the effectiveness of a psychosocial intervention based on Teaching Recovery Techniques (TRT) to increase resiliency among Palestinian children, exposed to a major trauma of war. Second, it analyses the role of family factors (maternal attachment and family atmosphere) as moderating the intervention impacts on resilience. School classes in Gaza were randomized into intervention (N = 242) and control (N = 240) groups. The percentage of girls (49.4%) and boys (50.6%) were equal, and the child age was 10–13 years in both groups. Children reported positive indicators of their mental health (prosocial behaviour and psychosocial well-being) at baseline (T1), post-intervention (T2) and at a six-month follow-up (T3). At T1 they accounted their exposure to war trauma. Mothers reported about their willingness to serve as an attachment figure, and the child reported about the family