Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

(1) Background: Clozapine is the most effective antipsychotic. It is, however, associated with many adverse drug reactions. Nose-to-brain (N2B) delivery offers a promising approach. This study aims to develop clozapine-encapsulated thermosensitive sol–gels for N2B delivery. (2) Methods: Poloxamer 407 and hydroxypropyl methylcellulose were mixed and hydrated with water. Glycerin and carbopol solutions were added to the mixture and stirred overnight at 2–8 °C. Clozapine 0.1% w/w was stirred with polysorbate 20 (PS20) or polysorbate 80 (PS80) at RT (25 °C) before being added to the polymer solution. The final formulation was made to 10 g with water, stirred overnight at 2–8 °C and then adjusted to pH 5.5. (3) Results: Formulations F3 (3% PS20) and F4 (3% PS80) were selected for further evaluation, as their gelation temperatures were near 28 °C. The hydrodynamic particle diameter of clozapine was 18.7 ± 0.2 nm in F3 and 20.0 ± 0.4 nm in F4. The results show a crystallinity change in clozapine to amorphous. Drug release studies showed a 59.1 ± 3.0% (F3) and 53.1 ± 2.7% (F4) clozapine release after 72 h. Clozapine permeated after 8 h was 20.8 ± 3.0% (F3) and 17.8 ± 3.1% (F4). The drug deposition was higher with F4 (144.8 ± 1.4 µg/g) than F3 (110.7 ± 2.7 µg/g). Both sol–gels showed no phase separation after 3 months. (4) Conclusions: Binary PS80-P407 mixed micelles were more thermodynamically stable and rigid due to the higher synergism of both surfactants. However, binary mixed PS20-P407 micelles showed better drug permeation across the nasal mucosa tissue and may be a preferable carrier system for the intranasal administration of clozapine.

Niosome encapsulated doxycycline-hyclate for potentiation of acne therapy: formulation and characterization

Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline-hyclate kills a wide range of bacteria. To prevent oral administration's side effects, overcome the barriers of conventional topical treatment, and improve the therapeutic effectiveness, doxycycline-hyclate was loaded into four niosomal formulations with different percentages of constituents (span 60 and cholesterol) prepared by the thin-film hydration method. Then, one of the four formulations with the most appropriate particle size of 362.88 ± 13.05 nm to target the follicles, percentage of drug entrapment efficiency of 56.3 ± 2.1%, in vitro drug release of 54.93 ± 1.99% after 32 hours, and the lowest permeation of the drug through the Wistar rat skin, was selected. Then, its toxicity on human dermal fibroblasts (HDF) by MTT method after 72 hours, its antibacterial activity against the main acne-causing bacteria via antibiogram test, and its effect on Wistar rat skin drug deposition were measured. Improved cell viability, increased antibacterial activity, and an approximately three-fold increase in drug deposition were the optimal niosomal formulation features relative to the free drug. Overall, this study demonstrated the ability of nano-niosomes containing doxycycline-hyclate to treat skin acne.

Anesthetic management of a parturient with Eisenmenger’s syndrome: A case report

Eisenmenger’s syndrome results from certain uncorrected congenital abnormalities of the heart facilitating left to right shunt and chronic volume overload of the pulmonary vasculature, leading to irreversible changes in the pulmonary vasculature. Pregnancy in the patients of this syndrome is associated with a high risk of cardiovascular decompensation, thromboembolic complications, and sudden cardiac death. We present the case of a 25-year-old pregnant woman with Eisenmenger’s syndrome who delivered through the vaginal route at 37 weeks of gestation, under labor epidural anesthesia. A healthy male baby was delivered within 40 min of drug deposition in the epidural space. The postpartum period was essentially uneventful with successful maternal and neonatal outcomes.

Development and Evaluations of Transdermally Delivered Luteolin Loaded Cationic Nanoemulsion: In Vitro and Ex Vivo Evaluations

Introduction: Luteolin (LUT) is natural flavonoid with multiple therapeutic potentials and is explored for transdermal delivery using a nanocarrier system. LUT loaded cationic nanoemulsions (CNE1–CNE9) using bergamot oil (BO) were developed, optimized, and characterized in terms of in vitro and ex vivo parameters for improved permeation. Materials and methods: The solubility study of LUT was carried out in selected excipients, namely BO, cremophor EL (CEL as surfactant), labrasol (LAB), and oleylamine (OA as cationic charge inducer). Formulations were characterized with globular size, polydispersity index (PDI), zeta potential, pH, and thermodynamic stability studies. The optimized formulation (CNE4) was selected for comparative investigations (% transmittance as %T, morphology, chemical compatibility, drug content, in vitro % drug release, ex vivo skin permeation, and drug deposition, DD) against ANE4 (anionic nanoemulsion for comparison) and drug suspension (DS). Results: Formulations such as CNE1–CNE9 and ANE4 (except CNE6 and CNE8) were found to be stable. The optimized CNE4 based on the lowest value of globular size (112 nm), minimum PDI (0.15), and optimum zeta potential (+26 mV) was selected for comparative assessment against ANE4 and DS. The %T values of CNE1–CNE9 were found to be ˃95% and CEL content slightly improved the %T value. The spherical CNE4 was compatible with excipients and showed % total drug content in the range of 97.9–99.7%. In vitro drug release values from CNE4 and ANE4 were significantly higher than DS. Moreover, permeation flux (138.82 ± 8.4 µg/cm2·h), enhancement ratio (8.23), and DD (10.98%) were remarkably higher than DS. Thus, ex vivo parameters were relatively high as compared to DS which may be attributed to nanonization, surfactant-mediated reversible changes in skin lipid matrix, and electrostatic interaction of nanoglobules with the cellular surface. Conclusion: Transdermal delivery of LUT can be a suitable alternative to oral drug delivery for augmented skin permeation and drug deposition.

Particle Image Velocimetry Measurements of a Dry Powder Inhaler Flow

Inhalation therapy for respiratory disorders is being increasingly delivered via dry powder inhalers (DPIs), which are breath-actuated devices that deliver pharmaceutical drug particles to the lungs. The motion of inhalation air, produced when a patient inhales through this device, supplies all energy for the entrainment, de-agglomeration, and dispersion of powder drug agglomerates into a fine drug particle aerosol. The aerosol performance is directly related to the fluid-mechanics of a given DPI device. These flow mechanisms are complex as they depend on the device design, inhalation flow rate, and the properties of the dry powder formulation used. Among these, the role of device design is crucial as it significantly affects not only the generation and properties of delivered aerosol, but also the capability of targeted regional drug deposition.

Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System

As pulmonary drug deposition is a function of aerosol particle size distribution, it is critical that the dynamics of particle formation and maturation in pMDI sprays in the interim between generation and inhalation are fully understood. This paper presents an approach to measure the evaporative and condensational fluxes of volatile components and water from and to solution pMDI droplets following generation using a novel technique referred to as the Single Particle Electrodynamic Lung (SPEL). In doing so, evaporating aerosol droplets are shown capable of acting as condensation nuclei for water. Indeed, we show that the rapid vaporisation of volatile components from a volatile droplet is directly correlated to the volume of water taken up by condensation. Furthermore, a significant volume of water is shown to condense on droplets of a model pMDI formulation (hydrofluoroalkane (HFA), ethanol and glycerol) during evaporative droplet ageing, displaying a dramatic shift from a core composition of a volatile species to that of predominantly water (non-volatile glycerol remained in this case). This yields a droplet with a water activity of 0.98 at the instance of inhalation. The implications of these results on regional and total pulmonary drug deposition are explored using the International Commission of Radiological Protection (ICRP) deposition model, with an integrated semi-analytical treatment of hygroscopic growth. Through this, droplets with water activity of 0.98 upon inhalation are shown to produce markedly different dose deposition profiles to those with lower water activities at the point of inspiration.

Recent Findings on Thymoquinone and its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ’s potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

Enrofloxacin and Ciprofloxacin Residues in Table Eggs: Distribution and Heat Treatment Effect

A 500 composite egg samples (2500 eggs-each sample represented by 5 eggs) collected from layer farms and local markets from all over Jordan were studied for presence of antimicrobials using Premi®Test screening test. Positive samples indicated by inhibition of microbial growth represented 12.8% out of total screened egg samples. Positive samples were examined quantitatively using HPLC technique to detect the presence of enrofloxacin and ciprofloxacin. Ciprofloxacin and enrofloxacin residues were detected in 1% and 0.8% of the total samples, respectively, where both drugs were recovered from white but not yolk. The effect of boiling on either drugs concentration in fortified white or yolk was demonstrated by gradual increases in the mean reduction percentages within treatment time with an average of 87% reduction after 15 minutes of boiling for both drugs and egg compartments and 5 minutes of frying at 160°C. The average concentration reduction percentages by the end of four weeks of refrigeration of fortified yolk and white were around 45 and 50% for enrofloxacin and ciprofloxacin respectively. The significance and mechanism of drug deposition and reduction during processing is being highlighted.