Screening of Cyclodextrins in the Processing of Buserelin Dry Powders for Inhalation Prepared by Spray Freeze-Drying.

Purpose: In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant carrier was combined with two levels of five different cyclodextrins (CDs) and then processed by SFD. Methods: Dry powder diameters were evaluated by laser light scattering and morphology was determined by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were utilized for the determination of crystalline structures. The aerodynamic properties of the spray freeze-dried powders were evaluated by twin stage impinger (TSI) and the stability of prepared samples was assessed under normal and accelerated conditions. Results: The prepared powders were mostly porous spheres and the size of microparticles ranged from 9.08 to 13.53 µm, which are suitable as spray-freeze dried particles. All formulations showed amorphous structure confirmed by DSC and XRD. The aerosolization performance of the formulation containing buserelin, raffinose and 5% beta-cyclodextrin (ß-CD), was the highest and its fine particle fraction (FPF) was 69.38%. The more circular and separated structures were observed in higher concentrations of CDs, which were compatible with FPFs. The highest stability was obtained in the formulation containing hydroxypropyl beta-cyclodextrin (HP-ß-16. CD) 5%. On the contrary, sulfobutylether beta-cyclodextrin (SBE-ß-CD) 5% bearing particles showed the least stability. Conclusion: By adjusting the type and ratio of CDs in the presence of raffinose, the prepared formulations could effectively enhance the aerosolization and stability of buserelin. Therefore, they can be proposed as a suitable career for lung drug delivery.

Efficacy of drug regimen with and without oseltamivir in hospitalized patients with COVID-19: A retrospective study.

Introduction: Coronavirus disease 2019 (COVID-19) is the most critical issue in nowadays medicine. We aimed to evaluate the use and therapeutic outcomes of oseltamivir, an antiviral drug for patients with COVID-19. Materials and method: In an observational study conducted at Imam Khomeini Hospital in Amol, Iran, data for 544 patients with laboratory and CT scan result confirmed COVID-19 were retrospectively collected between February 24th and April 13th 2020. To compare the characteristics of patients based on gender, the chi-square test was used. Logistic regression was used to evaluate the effect of oseltamivir on the outcome of treatment. Logrank test were used to compare the length of hospital stay in people treated with oseltamivir and drugs other than oseltamivir. Results: Kaplan-Meier and logrank test showed no significant reduction in hospitalization time and survival rate following treatment with oseltamivir. However, a significant increase in lymphocytes count and reduction of C-reactive protein (CRP) level detected. Conclusion: Administration of oseltamivir for patients with COVID-19 didn't show any improvement in hospitalization duration and survival rate.

Introducción: la enfermedad por coronavirus 2019 (COVID-19) es el tema más crítico en la medicina actual. Nuestro objetivo fue evaluar el uso y los resultados terapéuticos de oseltamivir, un medicamento antiviral para pacientes con COVID-19. Materiales y método: en un estudio observacional realizado en el Hospital Imam Khomeini en Amol, Irán, los datos de 544 pacientes con resultados de laboratorio y tomografía computarizada confirmados de COVID-19 se recopilaron retrospectivamente entre el 24 de febrero y el 13 de abril de 2020. Para comparar las características de los pacientes en función del género se utilizó la prueba de chi-cuadrado. Se utilizó regresión logística para evaluar el efecto de oseltamivir en el resultado del tratamiento. Se utilizó la prueba de rango logarítmico para comparar la duración de la estancia hospitalaria en personas tratadas con oseltamivir y otros fármacos distintos del oseltamivir. Resultados: Kaplan­Meier y la prueba de rango logarítmico no mostraron una reducción significativa en el tiempo de hospitalización y la tasa de supervivencia después del tratamiento con oseltamivir. Sin embargo, se detectó un aumento significativo en el recuento de linfocitos y una reducción del nivel de proteína C reactiva (PCR). Conclusión: la administración de oseltamivir para pacientes con COVID-19 no mostró ninguna mejora en la duración de la hospitalización y la tasa de supervivencia.

Spray freeze-drying for inhalation application: process and formulation variables.

High porous particles with specific aerodynamic properties were processed by the spray freeze-drying (SFD) method. Comprehensive knowledge about all aspects of the SFD method is required for particle engineering of various pharmaceutical products with good flow properties. In this review, different types of the SFD method, the most frequently employed excipients, properties of particles prepared by this method, and most recent approaches concerning SFD are summarized. Generally, this technique can prepare spherical-shaped particles with a highly porous interior structure, responsible for the very low density of powders. Increasing the solubility of spray freeze-dried formulations achieves the desired efficacy. Also, due to the high efficiency of SFD, by determining the different features of this method and optimizing the process by model-based studies, desirable results for various inhaled products can be achieved and significant progress can be made in the field of pulmonary drug delivery.

Long-time effects of prenatal morphine, tramadol, methadone, and buprenorphine exposure on seizure and anxiety in immature rats.

Purpose: This study aimed to investigate seizures and anxiety-like behaviors in immature rats prenatally exposed to opiate drugs.Materials and methods: Pregnant rats were randomly divided into five groups: saline, morphine, tramadol, methadone, and buprenorphine. Administrations were performed intraperitoneally once a day for the last seven days of pregnancy. Neonatal rats were subdivided into ten groups, split according to sex. Anxiety-like behavior was tested on postnatal day (PD) 19. On PD 20, seizure was induced by PTZ injection.Results: Morphine in male rats had an increased time to onset (p < 0.005), whereas there was a decreased number of tonic-clonic seizures in females (p < 0.05). Tramadol had an increased duration of tonic-clonic seizures compared to morphine and methadone in males (p < 0.005). Moreover, tramadol decreased open arm time and locomotor activity in males more than in females (p < 0.05). Methadone decreased open arm time in males (p < 0.05). Furthermore, buprenorphine and tramadol decreased open arm entrance in male rats (p < 0.05).Conclusions: It was demonstrated that prenatal tramadol significantly increases both the duration of seizures and anxiety-like behaviors in immature male rats, whereas morphine decreases both of them. The effects of tramadol on seizure and anxiety-like behavior may be due to the comorbid occurrence of the symptoms of these two disorders.

Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes.

The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 µg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 µg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.