Guiding Clinical Prescription of Topical Extemporaneous Formulations of Sodium Cromoglycate Based on Pharmaceutical Performance.

Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler's base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler's base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations.

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals.

3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

Ultradeformable Lipid Vesicles Localize Amphotericin B in the Dermis for the Treatment of Infectious Skin Diseases.

Cutaneous fungal and parasitic diseases remain challenging to treat, as available therapies are unable to permeate the skin barrier. Thus, treatment options rely on systemic therapy, which fail to produce high local drug concentrations but can lead to significant systemic toxicity. Amphotericin B (AmB) is highly efficacious in the treatment of both fungal and parasitic diseases such as cutaneous leishmaniasis but is reserved for parenteral administration in patients with severe pathophysiology. Here, we have designed and optimized AmB-transfersomes [93.5% encapsulation efficiency, 150 nm size, and good colloidal stability (-35.02 mV)] that can remain physicochemically stable (>90% drug content) at room temperature and 4 °C over 6 months when lyophilized and stored under desiccated conditions. AmB-transfersomes possessed good permeability across mouse skin (4.91 ± 0.41 µg/cm2/h) and 10-fold higher permeability across synthetic Strat-M membranes. In vivo studies after a single topical application in mice showed permeability and accumulation within the dermis (>25 µg AmB/g skin 6 h postadministration), indicating the delivery of therapeutic amounts of AmB for mycoses and cutaneous leishmaniasis, while a single daily administration in Leishmania (Leishmania) amazonensis infected mice over 10 days, resulted in excellent efficacy (98% reduction in Leishmania parasites). Combining the application of AmB-transfersomes with metallic microneedles in vivo increased the levels in the SC and dermis but was unlikely to elicit transdermal levels. In conclusion, AmB-transfersomes are promising and stable topical nanomedicines that can be readily translated for parasitic and fungal infectious diseases.

Assessing risk of opioid misuse in the treatment of chronic pain: Building a practical actuarial approach.

OBJECTIVE: Opioid misuse risk assessment has been highlighted as an important part of clinical practice, but there is a paucity of research identifying an effective approach to assessment. Currently, practitioners use patient history, interviews, and formal questionnaires, and these data are weighed clinically to assign risk. The authors propose the use of an actuarial method-the Bayesian nomogram-as a simple, standard, evidence-based approach to opioid misuse risk assessment. INTERVENTIONS: The Bayesian nomogram relies solely on empirically established relationships between risk factors and risk and has been found in other fields to be both more efficient and more consistent than clinical judgment. The authors performed a comprehensive search of the literature to identify empirically established risk factors for opioid misuse in the treatment of noncancer chronic pain. RESULTS: As the Bayesian nomogram requires both base rates of the predicted event (opioid misuse) and odds ratios for risk factors, the authors reported the most current evidence available in the literature. The authors also included the nomogram itself for easy clinical application of base rates and risk factors in the predictive model. Finally, the authors provided examples to help illustrate practical application. CONCLUSIONS: The authors call for research comparing this methodology to "assessment as usual" to better predict risk of opioid misuse and to aid decision making for medical providers treating chronic-pain patients.