A critical review on the availability of substandard and falsified medicines online: Incidence, challenges and perspectives.

Simultaneous expansion of the Internet and increased globalisation of the pharmaceutical industry have meant medication can be accessed transnationally from both legal and illicit sources. This has coincided with the rise of substandard and falsified medicines (SFMs) online. These products fail to meet regulatory or quality standards and/or are constituted with substandard ingredients, causing undesired pharmacological effects, including possible injury and death. This review aimed to identify original research studies that examined characteristics of SFM online sales, attitudes towards purchasing medicines online and strategies to address this drug safety challenge. Keywords of 'Substandard' and 'Falsified'/'Counterfeit' and 'Medicines'/'Drugs' and 'Online'/'Internet' were searched using Web of Knowledge and PubMed databases. Resulting literature, which satisfied the study's inclusion criteria, was included in the review, and the findings from each paper were assessed. From an initial 185 literature articles, 7 were eligible according to the inclusion criteria to be reviewed. These articles identified studies testing SFMs purchased online, surveys of attitudes and knowledge about SFMs online, and website content analysis to detect illegal online sales. Challenges identified were lack of knowledge and awareness among consumers and physicians, in addition to the use of direct-to-consumer-advertising, via Internet platforms and social media, providing easy access to SFMs. Despite this, medicine authentication technology, website verification approaches and new detection methods were identified as potential solutions specific to online SFM sales. To address online sales of SFMs, more robust research, greater awareness/educational programmes, analytical detection methods and more stringent online global governance are required.

3D-Printed Solid Dispersion Drug Products.

With the well-known advantages of additive manufacturing methods such as three-dimensional (3D) printing in drug delivery, it is disappointing that only one product has been successful in achieving regulatory approval in the past few years. Further research and development is required in this area to introduce more 3D printed products into the market. Our study investigates the potential of fixed dose combination solid dispersion drug products generated via 3D printing. Two model drugs-fluorescein sodium (FS) and 5-aminosalicyclic acid (5-ASA)-were impregnated onto a polyvinyl alcohol (PVA) filament, and the influence of solvent choice in optimal drug loading as well as other influences such as the physicochemical and mechanical properties of the resultant filaments were investigated prior to development of the resultant drug products. Key outcomes of this work included the improvement of filament drug loading by one- to threefold due to solvent choice on the basis of its polarity and the generation of a 3D-printed product confirmed to be a solid dispersion fixed dose combination with the two model drugs exhibiting favourable in vitro dissolution characteristics.

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery.

In order to evaluate the potential of a technology platform based on hyaluronan copolymers grafted with propargylated ferulate fluorophores (HA-FA-Pg) in the development of drug delivery systems, the propargyl groups of HA-FA-Pg derivatives were employed with oleic acid (OA) or stearic acid (SA) residues across a biocompatible hexa(ethylene glycol) (HEG) spacer. The designed materials (i.e., HA-FA-HEG-OA or HA-FA-HEG-SA) showed clear-cut aggregation features in an aqueous environment, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), generating nanoaggregate systems. In fact, HA-FA-HEG-OA and HA-FA-HEG-SA derivatives showed the property to create self-assembled cytocompatible nanostructured aggregates in water, thanks to the simultaneous presence of hydrophilic portions in the polymeric backbone, such as hyaluronic acid, and hydrophobic portions in the side chains. Furthermore, the designed materials interact with living cells showing a high degree of cytocompatibility. The potential ability of nanosystems to load pharmacologically active molecules was assessed by the physical entrapment of olanzapine into both polymeric systems. The drug loading evaluation demonstrated that the nanoparticles are able to incorporate a good quantity of olanzapine, as well as improve drug solubility, release profile, and cytocompatibility.

Engineering of Nanofibrous Amorphous and Crystalline Solid Dispersions for Oral Drug Delivery.

Poor aqueous solubility (<0.1 mg/mL) affects a significant number of drugs currently on the market or under development. Several formulation strategies including salt formation, particle size reduction, and solid dispersion approaches have been employed with varied success. In this review, we focus primarily on the emerging trends in the generation of amorphous and micro/nano-crystalline solid dispersions using electrospinning to improve the dissolution rate and in turn the bioavailability of poorly water-soluble drugs. Electrospinning is a simple but versatile process that utilizes electrostatic forces to generate polymeric fibers and has been used for over 100 years to generate synthetic fibers. We discuss the various electrospinning studies and spinneret types that have been used to generate amorphous and crystalline solid dispersions.

Solid microcrystalline dispersion films as a new strategy to improve the dissolution rate of poorly water soluble drugs: A case study using olanzapine.

In this study, we evaluate the dissolution rate enhancement of solid microcrystalline dispersion (SMD) films of olanzapine (OLZ) formulated with four water-soluble polymers namely poly(N-vinylpyrrolidone) (PVP), poloxamer 188 (P188), poloxamer 407 (P407) and Soluplus(®) (SLP). Prepared formulations were characterised to determine particle size, morphology, hydrogen bonding interactions, thermal characteristics as well as in vitro dissolution studies conducted under sink conditions (pH 6.8). Particle size of OLZ in all formulations ranged between 42 and 58µm. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Hot-Stage Microscopy (HSM) studies confirmed OLZ was well maintained in its crystalline state during the formulation process. In vitro dissolution studies showed immediate drug release from all formulation when compared to the drug alone. The greatest increase in in vitro dissolution rate was observed in formulations containing P188 most likely due to its enhanced hydrophilic and surfactant properties compared to the other agents used. Overall, this study successfully generated OLZ loaded SMD films with improved in vitro dissolution rates which is highly likely to result in improved oral bioavailability in vivo.