Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Comparación de los efectos del D-004, imipramina y sertralina en el modelo de nado forzado en ratones / Comparative effects of D-004, Imipramine and Sertraline in the forced swimming test in mice

Introducción: La finasterida, inhibidor de la 5 a-reductasa, se emplea en el tratamiento de la hiperplasia prostática benigna, y ocasiona entre sus efectos adversos un aumento de cuadros de depresión. El D-004 es un extracto lipídico extraído a partir del fruto de la palma real (Roystonea regia), inhibe la 5 a-reductasa y previene la hiperplasia prostática benigna, y muestra un efecto antidepresivo moderado en el ensayo de nado forzado y suspensión por la cola. Objetivo: comparar el efecto del D-004 con la imipramina y la sertralina sobre la duración de las conductas de inmovilidad, nado y escalado en el ensayo de nado forzado. Métodos: se distribuyeron los ratones en ocho grupos: control (vehículo), tres tratados con D-004 (100, 250 y 500 mg/kg), dos con sertralina y dos con imipramina (30 y 50 mg/kg) respectivamente. Estos se colocaron en un cilindro de cristal que contenía agua a una altura de 6 cm y se cuantificaron las conductas. Resultados: la administración oral de D-004 (100, 250 y 500 mg/kg) durante 14 días redujo significativamente el tiempo de inmovilidad con respecto al grupo control (17, 22 y 25 porciento) y aumentó significativamente la conducta de nado en 1,58, 1,68 y 1,74 veces. Este efecto resulta moderado (25 porciento) comparado con las reducciones alcanzadas por la sertralina y la imipramina (³ 60 porciento). Las dosis mayores (250 y 500 mg/kg) ocasionaron incrementos de la conducta de escalado, 2,79 y 3,55 veces superiores a la del grupo control, lo que mostró semejanza con la imipramina, aunque con una menor eficacia. Conclusiones: el D-004 ejerce un moderado efecto antidepresivo, lo que pudiera contribuir al manejo de los pacientes con hiperplasia prostática benigna en los cuales se informa coincidencia de cuadros depresivos

Introduction: Finasteride is a 5 a-reductase inhibitor to treat benign prostatic hyperplasia (BPH) and one of the adverse effects is the increase of depressive symptoms. D-004 is a lipid extract from the real palm fruit (Roystonea regia) that is effective to prevent prostatic hyperplasia by inhibiting 5 a-reductase and shows moderate antidepressant effects in the forced swimming test (FST) and tail suspension test. Objective: to compare the effects of D-004, Imipramine and Sertraline on the duration of behaviours under conditions of immobility, swimming and climbing in the forced swimming test. Methods: mice were randomly distributed in 8 groups: control (vehicle), 3 treated with D-004 (100, 250 and 500 mg/kg), 2 with Sertraline and 2 with Imipramine (30 and 50 mg/kg) respectively. Mice were placed in a glass cylinder containing 6 cm high column of water and their behaviours were quantified. Results: oral administration of D-004 (100, 250 and 500 mg/kg) during 14 days reduced the length of time of immobility with respect to the control group (17, 22 and 25 percent), and significantly increased the behaviours at swimming by 1.58, 1.68 and 1.74 times. This is a moderate effect (25 percento) if compared with Sertraline and Imipramine (³ 60 percent) The doses of 250 and 500 mg/kg showed that climbing behaviours were 2.79 and 3.55 times higher than the control group. The results were similar to those of Imipramine but less effective. Conclusions: D-004 showed moderate antidepressant effect. This fact could help in the treatment of patients with benign prostatic hyperplasia, who reported similar depressive status

Spectrophotometric and spectrofluorimetric determination of some selective serotonin reuptake inhibitors [SSRIs] through ternary complex formation with eosin and copper [II] in pharmaceuticals

Two simple, and sensitive, spectrophotometric and spectrofluorimetric procedures have been developed and validated for analysis of selective serotonin reuptake inhibitors [SSRIs] namely, fluoxetine hydrochloride [FX], fluvoxamine maleate [FV] and sertraline hydrochloride [SE]. Both methods were based on the formation of ternary complex between the cited drugs, eosin and copper sulphate, Spectrophotometrically, the complex was estimated by two procedures, the first procedure depends on the extraction of the ternary complex with chloroform. The second spectrophotometric one depends on the direct measurement of the complex after addition of sodium lauryl sulphat. The ternary complexes showed an absorption maximum at 530 nm for the three cited drugs. Different variables and parameters affecting the reactions were studied and optimized. The formed complexes obey Beer's law in concentration range 1-18, 1-16, 0.25-10 micro gml[-1] using the extractive method and 0.4-12, 0.5-14, 0.1-8 micro gml-1 using surfactant with good correlation coefficients. A fluorescence quenching method for the determination of the [SSRIs] through the formed ternary complexes was also investigated to enhance the sensitivity of the analysis. The formed fluorophores were measured at lambda E[x] 310 nm and lambda E[m]510nm for the three drugs. Regression analysis showed good correlation coefficients [0.9996-0.9999] over the concentration ranges 0.1-25, 0.1-15 and 0.1-12 micro gml-1 for FX, FV and SE, respectively. The proposed methods were validated and successfully applied to the analysis of the three drugs in drug substances and drug products with good accuracy. No interference was observed from common pharmaceutical excipients. The results were favorably in good agreement with those obtained by official methods