Development and validation of an HPLC-UV method for accelerated stability study and pharmacokinetic analysis of venlafaxine

A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 µm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min−1. UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 ºC under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL−1; LOQ: 105 ng mL−1) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: tmax was 2.5h, Cmax was 56.5 µg mL−1, t1/2 was 8.2 h, AUC0-36 was 845.9 µg h mL−1. The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.

Acute toxicity study of a polysaccharide based hydrogel from linseed for potential use in drug delivery system

ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.

Appraisal of acute oral toxicity of glucuronoxylan hydrogel from Mimosa pudica seeds

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits.

Frequency of different infections in patients with hepatic encephalopathy due to cirrhosis liver

Objective: To determine frequency of different infections in patients with hepaticencephalopathy due to cirrhosis liver

Study Design: Cross sectional descriptive study

Place and Duration of Study: The study was conducted in the Department of Medicine, Combined Military Hospital, Peshawar over six months from April to October 2013

Patients and Methods: All patients with cirrhosis of liver of more than 18 years of age, manifesting signs of hepatic encephalopathy [HE] were included in the study. Detailed history, clinical examination and thorough investigations were done to look for different infections and the findings were recorded on a proforma. Descriptive statistics were used for data analysis

Results: One hundred and eighty five patients [70.81% males and 29.19% females] were enrolled. The mean age of the study subject was 49.2 +/- 3 years. Frequency of infections in the studied population was, spontaneous bacterial peritonitis [31.94%], UTI [25.00%], pneumonia [20.83%], sepsis [8.33%] and others infections [13.90%] like cholangitis, bronchitis, endocarditis, meningitis, and gastroenteritis

Conclusions: This study concluded that a substantial number of patients with hepatic encephalopathy due to cirrhosis liver have infections

Frequency of hypertriglyceridemia in newly diagnosed type 2 diabetics

Objective: To determine the frequency of hypertriglyceridemia in newly diagnosed type 2 diabetics presenting to tertiary care hospital

Study Design: Cross sectional descriptive study

Place and Duration of Study: This study was carried out at Department of Medicine, Military Hospital Rawalpindi from Nov 2010 to May 2011

Material and Methods: A total of 193 patients were recruited in this study from medical outpatient department and medical wards. Patients aged more than 30 years and of both sexes who were diagnosed diabetics in the past 6 months were included in the study

Results: Mean age of the patients was 49.1 +/- 7.3 years. Regarding gender distribution, 135 patients [70.0%] were male while remaining 58 patients [30.0%] were female. Out of total 193 patients, hypertriglyceridemia was present in 112 patients [58.0%]. Mean fasting blood glucose was 8.29 +/- 0.69 mmol/l, 2 hours post-prandial blood glucose 14.59 +/- 1.71 mmol/l, fasting serum triglyceride level was 2.27 +/- 0.35 mmol, 2 hours postprandial serum triglyceride level was 3.17 +/- 0.54 mmol

Conclusion: Frequency of hypertriglyceridemia in type 2 diabetics was found to be reasonably high in present study

Effects of STZ-induced diabetes on the relative weights of kidney, liver and pancreas in albino rats: a comparative study / Efectos de la diabetes inducida por STZ en los pesos relativos de riñón, hígado y páncreas en ratas albinas: un estudio comparativo

We studied the effects of streptozotocin (STZ)-induced diabetes on the body weights of animals and the relative weights of kidney, liver and pancreas in albino rats. The aim of the study was to find an association between the reduction in the body weights of diabetic animals and the relative weights of kidney, liver and pancreas in proportion to the body weight of animals in albino rats. This study was performed in the Department of Anatomy and Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi and Pathology department of College of Physicians & Surgeons (CPSP) Pakistan in 2007-08. Diabetes was induced by a single dose of STZ (45 mg/kg, b.w.) given intraperitoneally in sodium citrate buffer at pH 4.5. Eighty albino rats were divided into five groups: control (A) and STZ treated (B, C, D, and E) which were sacrificed 2, 4, 6 and 8 weeks post treatment respectively. All the animals were weighed prior to the administration of streptozotocin and at sacrificial time. Kidney, liver and pancreas were removed, dried and weighed on Sartorius balance. The body weights of animals in different groups changed at variable time intervals. The Kidney weight was significantly increased, liver weight was slightly increased while the weight of pancreas was unaffected when compared with the weight of diabetic animals. It seems that the STZ-induced diabetes causes a significant reduction in the body weight of diabetic animals while the relative weights of kidney and liver were increased and the weight of pancreas was unaffected.

Se estudiaron en ratas albinas los efectos de la diabetes inducida por estreptozotocina (STZ) sobre el peso corporal de los animales y los pesos relativos de riñón, hígado y páncreas . El objetivo del estudio fue encontrar una asociación entre la reducción del peso corporal de los animales diabéticos y los pesos relativos de riñón, hígado y páncreas en proporción al peso corporal de los animales. Este estudio fue realizado en el Departamento de Anatomía, Instituto de Ciencias Farmacéuticas, Universidad Médica Baqa y Departamento de Anatomía Patológica del Colegio de Médicos y Cirujanos Pakistán (CPSP) en 2007-08. La diabetes fue inducida por una dosis única de STZ (45 mg / kg de peso corporal) administrados por vía intraperitoneal en tampón de citrato de sodio a pH 4,5. Ochenta ratas Wistar se dividieron en cinco grupos: control (A) y STZ tratadas (B, C, D y E), que se sacrificaron 2, 4, 6 y 8 semanas después del tratamiento respectivamente. Todos los animales fueron pesados antes de la administración de estreptozotocina, y en el momento del sacrificio. El riñón, hígado y páncreas fueron removidos, secados y pesados sobre una balanza Sartorius. El peso corporal de los animales en los diferentes grupos cambió en intervalos de tiempo variables. El peso del riñón aumentó significativamente, el peso del hígado se incrementó ligeramente, mientras que el peso del páncreas no se modificó en comparación con el peso de los animales diabéticos. Parece que la diabetes inducida por STZ causa una reducción significativa del peso corporal de los animales diabéticos, mientras que el peso relativo de los riñones y elhígado se incrementaron y el peso de páncreas no se vio afectado.

Altered liver morphology and enzymes in streptozotocin induced diabetic rats / Morfología y enzimas del hígado alteradas en ratas con diabetes inducida por estreptozotocina

This study was undertaken to evaluate the relationship and effects of diabetes on liver morphology, architecture and function. The hepatic effects of diabetes were evaluated in vivo using streptozotocin (STZ)-induced diabetic rats as an experimental model. The degree of hepatic dysfunction was measured by using biochemical parameters like serum transaminases (ALT and AST), alkaline phosphatase (ALP)and pseudocholinesterase (PChE) while the histopathological studies were carried out to support the enzymic Parameters. The aim of the study was to investigate the association between diabetic hepatic complications and liver enzyme alterations. This study was performed in the Department of Anatomy; Institute of Pharmaceutical Sciences and Institute of Diabetology and endocrinology of Baqai Medical University, Karachi. Diabetes was induced by a single dose of STZ (45 mg/kg, b.w.) given intraperitoneally in sodium citrate buffer at pH 4.5. Eighty albino rats were divided into five groups: control (A) and STZ treated (B, C, D, and E) which were sacrificed 2, 4, 6 and 8 weeks post treatment respectively. Histopathological examination of liver showed accumulation of lipid droplets, lymphocytic infiltration, increased fibrous content, dilatation and congestion of portal vessels and proliferation of bile ducts. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP and PChE were observed in the liver. It seems that the diabetic complications in the liver like hepatocyte destruction etc. are likely to be due to alterations in enzyme levels.

Este estudio se realizó para evaluar la relación y los efectos de la diabetes sobre la morfología, arquitectura y la función del hígado. Los efectos hepáticos de la diabetes se evaluaron in vivo utilizando estreptozotocina (STZ) para inducir diabetes en ratas como un modelo experimental. El grado de disfunción hepática se midió mediante el uso de parámetros bioquímicos, como las transaminasas séricas (ALT y AST), fosfatasa alcalina (ALP) y pseudocolinesterasa (PChE), mientras que los estudios histopatológicos se llevaron a cabo para apoyar los parámetros enzimáticos. El objetivo del estudio fue investigar la asociación entre las complicaciones hepáticas diabéticas y la alteración de enzimas hepáticas. Este estudio se realizó en el Departamento de Anatomía, Instituto de Ciencias Farmacéuticas y el Instituto de Diabetología y Endocrinología de la Baqai Medical University, Karachi. La diabetes fue inducida por una dosis única de STZ (45 mg/kg de peso corporal) administrada por vía intraperitoneal en tampón citrato de sodio a pH 4,5. Ochenta ratas albinas se dividieron en cinco grupos: control (A) y tratados con STZ (B, C, D y E), las que se sacrificaron a las 2, 4, 6 y 8 semanas después del tratamiento. El examen histopatológico de hígado mostró acumulación de gotitas de lípidos, infiltración linfocítica, aumento del contenido de fibras, dilatación y congestión de los vasos portales, y la proliferación de conductos biliares. Aumento de los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), ALP y PChE fueron observados en el hígado. Parece que las complicaciones de la diabetes en el hígado como la destrucción de los hepatocitos etc., son probablemente debido a alteraciones en los niveles de las enzimas.

Altered kidney morphology and enzymes in streptozotocin induced diabetic rats / Morfología y enzimas renales alteradas en ratas con diabetes inducida por estreptozotocin

We studied the effects of streptozotocin (STZ)-induced diabetes on kidney morphology, anatomy, architecture and on the activities of aminotransferases (AST and ALT), alkaline phosphatase (ALP) and pseudocholinesterase (PChE) in albino rats. The aim of the study was to investigate the association between diabetic kidney complications and kidney enzyme alterations. This study was performed in the Department of Anatomy and Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi and Pathology department of College of Physicians & Surgeons (CPSP) Pakistan in 2007-08. Diabetes was induced by a single dose of STZ (45 mg/kg, b.w.) given intraperitoneally in sodium citrate buffer at pH 4.5. Eighty (80) albino rats were divided into five groups: control (A) and STZ treated (B, C, D, and E) which were sacrificed 2, 4, 6 and 8 weeks post treatment respectively. Histopathology of kidney showed lesions similar to human glomerulosclerosis, glomerular membrane thickening, arteriolar hyalinization and tubular necrosis. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and pseudocholinesterase (PChE) were observed in the kidney. It seems that the diabetic complications in the kidney are likely to be associated with alterations in enzyme levels.

Se estudiaron los efectos de la diabetes inducida por estreptozotocin (STZ) sobre la morfología, anatomía, arquitectura y sobre las actividades de aminotransferasas (ALT y AST), fosfatasa alcalina (ALP) y pseudocolinesterasa (PChE) en los riñones de ratas albinas. El objetivo del estudio fue investigar la asociación entre las complicaciones renales diabéticas y la alteración de las enzimas renales. Este estudio se realizó en el Departamento de Anatomía y el Instituto de Ciencias Farmacéuticas, Universidad de Medicina Baqai, Karachi y el departamento de Patología de Colegio de Médicos y Cirujanos (CPSP) Pakistán entre el 2007-2008. La diabetes fue inducida por una dosis única de STZ (45 mg / kg de peso corporal) administrada por vía intraperitoneal en tampón de citrato de sodio a pH 4.5. Ochenta (80) ratas albinas fueron divididas en cinco grupos: control (A) y STZ tratados (B, C, D y E), que se sacrificaron a las 2, 4, 6 y 8 semanas después del tratamiento, respectivamente. La histopatología del riñón mostró lesiones similares a la glomeruloesclerosis en humanos, engrosamiento de la membrana glomerular, hialinización arteriolar y necrosis tubular. Aumento de los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), fosfatasa alcalina (ALP) y pseudocolinesterasa (PChE) fueron observados en el riñón. Parece que las complicaciones de la diabetes en el riñón están directamente asociadas con alteraciones en los niveles de las enzimas.