Potential protective effects of Acacia nilotica (L.) against gentamicin - induced nephrotoxicity by suppressing renal redox imbalance, inflammatory stress and caspase-dependent apoptosis in Wistar rats.

Gentamicin-induced nephrotoxicity limits its therapeutic use as an effective aminoglycoside. Herbal drugs have a distinct place in the world of pharmaceuticals since they are safe, effective, and cost-efficient. Acacia nilotica (L.) has long been recognized for its antihypertensive, antioxidant, anti-inflammatory, and antiplatelet aggregatory benefits in traditional medicine. Still, the protective effect of Acacia nilotica on gentamicin-induced nephrotoxicity is still unknown. Thus, the goal of this research was to examine the protection of ethanolic extract of Acacia nilotica (ANE) against nephrotoxicity triggered by Gentamicin.Thirty-six rats were randomly divided into six groups containing six rats in each group. The distilled water were given in control group. The rats in groups two and three were administered metformin and gentamicin respectively. In groups five and six, rats were administered ANE at doses of 100 and 200 mg/kg. Ten days of daily treatments were given. The urea, creatinine, uric acid, and LDH levels were analyzed on serum, whereas histological evaluation, MDA, GSH, SOD, CAT, TNF-α, IL-6, and caspase-3, were performed on kidney tissue on day 11. The gentamicin-treated group exhibited a significantly elevated MDA, and lower levels of antioxidant enzymes. Kidney function markers, inflammatory markers and caspase-3 expression were significantly elevated in the gentamicin-treated group. ANE significantly restored kidney function biomarkers, upregulated biochemical levels, inhibited TNF-α, caspase-3, cytokine expression, and reduced histological lesions.In conclusion, ANE has the ability to prevent gentamicin-induced nephrotoxicity and reduce nephrotoxic damage. As such, it may represent an effective therapy for patients receiving gentamicin treatment.

siRNA-Based Novel Therapeutic Strategies to Improve Effectiveness of Antivirals: An Insight.

Since the ground-breaking discovery of RNA interference (RNAi), scientists have made significant progress in the field of small interfering RNA (siRNA) treatments. Due to severe barriers to the therapeutic application of siRNA, nanoparticle technologies for siRNA delivery have been designed. For pathological circumstances such as viral infection, toxic RNA abnormalities, malignancies, and hereditary diseases, siRNAs are potential therapeutic agents. However, systemic administration of siRNAs in vivo remains a substantial issue due to a lack of "drug-likeness" (siRNA are relatively larger than drugs and have low hydrophobicity), physiological obstacles, and possible toxicities. This write-up covers important accomplishment in the field of clinical trials and patents specially based of siRNAs using targeting viruses. Furthermore, it offers deep insight of nanoparticle applied for siRNA delivery and strategies to improve the effectiveness of antivirals.

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, w/w) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.

Estimation of time since death from electrolyte, glucose and calcium analysis of postmortem vitreous humour in semi-arid climate.

Estimating time since death (TSD) with fair accuracy from postmortem changes still remains an important but difficult task to be performed by every autopsy surgeon in medicolegal scenario. The aim of the present study was to estimate TSD from electrolyte analysis of postmortem vitreous humour collected from samples under semi-arid climate. Vitreous humour was collected from 210 dead bodies brought to University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, during the period of November 2010 to April 2012. The vitreous samples were analysed for sodium, potassium, calcium, chloride and glucose. The results showed a significant positive relationship between TSD and potassium (r = 0.841, p = 0.000) and a weak negative relationship between TSD and sodium (r = -0.137, p = 0.048) and glucose (r = -0.241, p = 0.000), whereas no significant relationship could be established between TSD and calcium (r = 0.055, p = 0.429) and chloride (r = 0.075, p = 0.11).

Evaluation of CRP/Albumin Ratio in Polycystic Ovarian Syndrome.

Background: Polycystic ovarian syndrome is a common endocrine disorder among women of reproductive age. It is characterized by menstrual abnormalities, hyperandrogenism and polycystic ovaries and can lead to many complications. Studies have postulated the role of inflammation in the pathophysiology of PCOS. As acute phase reactants often serve as markers of inflammation, this study aimed to evaluate the role of inflammatory markers in women with PCOS and healthy controls. Material and Methods: A total of 60 participants were enrolled; 30 cases of PCOS and 30 age matched healthy controls. Peripheral venous blood was collected for assessment of CRP, serum albumin, serum total testosterone, serum fasting insulin and fasting blood glucose, following which statistical analysis was done. Results: The CRP/albumin ratio was found to be significantly higher in women with PCOS as compared to healthy controls along with serum total testosterone and HOMA-IR. Correlation between CRP/albumin ratio and the levels of serum total testosterone and insulin resistance was found to be non-significant. Conclusion: An elevated CRP/albumin ratio in cases of PCOS compared to healthy controls supports the hypothesis of inflammation playing a key role in the pathophysiology of PCOS. CRP/albumin ratio can serve as a cheaper biochemical marker of the disease subject to further validation studies to establish its use in Indian population.

The Anti-ulcer Potential of Weissella cibaria Assisted Bio-fermented Product of Citrus limetta Waste Peel in Wistar Albino Rats.

BACKGROUND: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity. OBJECTIVE: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment. METHODS: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w). RESULTS: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 µmol/mg protein vs. 454.49 ± 155.88 µmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14). CONCLUSION: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented.

Formulation of Phytosomes Containing Rubia cordifolia Extract for Neuropathic Pain: In Vitro and In Vivo Evaluation.

This study aimed to develop a delivery system for the dried aqueous extract of Rubia cordifolia leaves (RCE) that could improve the neuroprotective potential of RCE by improving the bioavailability of the chief chemical constituent rubiadin. Rubiadin, an anthraquinone chemically, is a biomarker phytoconstituent of RCE. Rubiadin is reported to have strong antioxidant and neuroprotective activity but demonstrates poor bioavailability. In order to resolve the problem related to bioavailability, RCE and phospholipids were reacted in disparate ratios of 1:1, 1:2, and 1:3 to prepare phytosome formulations PC1, PC2, and PC3, respectively. The formulation PC2 showed particle size of 289.1 ± 0.21 nm, ζ potential of -6.92 ± 0.10 mV, entrapment efficiency of 72.12%, and in vitro release of rubiadin of 89.42% at pH 7.4 for a period up to 48 h. The oral bioavailability and neuroprotective potential of PC2 and RCE were assessed to evaluate the benefit of PC2 formulation over the crude extract RCE. Formulation PC2 showed a relative bioavailability of 134.14% with a higher neuroprotective potential and significantly (p < 0.05) augmented the nociceptive threshold against neuropathic pain induced by partial sciatic nerve ligation method. Antioxidant enzyme levels and histopathological studies of the sciatic nerves in various treatment groups significantly divulged that PC2 has enough potential to reverse the damaged nerves into a normal state. Finally, it was concluded that encapsulated RCE as a phytosome is a potential carrier system for enhancing the delivery of RCE for the efficient treatment of neuropathic pain.

Recent Updates on the Development of Therapeutics for the Targeted Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complicated, multifaceted, irreversible, and incurable neurotoxic old age illness. Although NMDA (N-methyl D-aspartate)-receptor antagonists, cholinesterase repressors, and their pairings have been approved for the treatment, they are useful for short symptomatic relief. Researchers throughout the globe have been constantly working to uncover the therapy of Alzheimer's disease as new candidates must be determined, and newer treatment medicines must be developed. The aim of this review is to address recent advances in medication research along with new Alzheimer's disease therapy for diverse targets. Information was gathered utilizing a variety of internet resources as well as websites, such as ALZFORUM (alzforum.org) and clinicaltrials.gov. In contrast to other domains, the proposed medicines target amyloids (secretases, A42 generation, neuroinflammation, amyloid precipitation, and immunization), tau proteins (tau phosphorylation/aggregation and immunotherapy), and amyloid deposition. Despite tremendous advancement in our understanding of the underlying pathophysiology of Alzheimer's disease, the FDA (Food and Drug Administration) only approved aducanumab for diagnosis and treatment in 2003. Hence, novel treatment tactics are needed to find and develop therapeutic medicines to combat Alzheimer's disease.

PINK1 and oxidative stress in lean and obese patients with type 2 diabetes mellitus.

AIM: To compare mRNA [messenger RNA] expression of PINK1 in whole blood and the levels of biomarkers of Oxidative Stress (mitochondrial DNA [mtDNA] content & Total Antioxidant status [TAS]) in newly diagnosed lean and obese patients with T2DM. METHODS: Newly diagnosed patients of T2DM were enrolled in this study. The patients were divided into two groups of 30 patients each, lean (BMI < 18.5 kg/m2) and obese (BMI > 25 kg/m2). mRNA expression of PINK1 & mtDNA content was measured by real time PCR. Serum TAS was measured using a commercially available kit. RESULTS: There was a 1.78-fold decrease in mRNA expression of PINK1 in obese group compared to the lean group. Mean mtDNA content was 300.82 ± 169.66 in the obese group and 332.78 ± 147.07 in the lean group (p = 0.06). Mean levels of TAS was 5.39 ± 2.28 µM Trolox Equivalents in the obese group and 3.85 ± 3.33 µM Trolox Equivalents in the lean group (p = 0.001). CONCLUSION: The T2DM patient with obesity had greater OS than the lean patients. Thus, there is a compensatory increase in antioxidants in obese patients with T2DM. Our findings also suggest that decreased levels of PINK1 in obese group are unable to protect the mitochondria against OS leading to decreased mtDNA content. Does it also result in beta cell dysfunction or contribute to insulin resistance in obese patients with T2DM needs to be explored.

Differential Expression of Suppressor of Cytokine Signaling and Interferon Gamma in Lean and Obese Patients with Type 2 Diabetes Mellitus.

Background: The model of obesity-induced insulin resistance has long been used to explain the development of type 2 diabetes mellitus (T2DM) in obese individuals (body mass index (BMI) > 25 kg/m2), but this model failed to explain the development of the disease in lean individuals (BMI < 18.5 kg/m2). Defects in the insulin signaling pathway have been postulated to play a role in these patients, particularly in suppressors of cytokine signaling (SOCS) proteins, which are involved in the downregulation of insulin transduction. The expression of SOCS is also known to be induced by cytokines such as interferon gamma (IFN-γ). It is still not clear whether these pathways operate differently in lean versus obese patients with T2DM. Therefore, this pilot study was designed to study the expression of SOCS1, SOCS3, and IFN-γ in lean and obese patients with T2DM. Objectives: The levels of IFN-γ in serum and the messenger RNA (mRNA) expression of SOCS (SOCS1 and SOCS3) and IFN-γ genes in whole blood in lean and obese patients with T2DM. Methods: Sixty newly diagnosed T2DM patients (not on any pharmacotherapy) were enrolled and divided into 2 groups of lean (BMI < 18.5 kg/m2) and obese (BMI > 25 kg/m2) patients (n = 30 per group). Serum IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA), and mRNA expression of IFN-γ, SOCS1, and SOCS3 was measured by real-time polymerase chain reaction (PCR) using the ∆∆ Ct method. Results: Serum IFN-γ levels were 10.83 ± 5.81 pg/mL in the lean group and 9.35 ± 5.14 pg/mL in the obese group (P = 0.02). Fasting serum insulin levels were 16.07 ± 8.39 µIU/mL in the lean group and 27.11 ± 4 .91 µIU/mL in the obese group (P = 0.001). There was a 3.16-fold increase in mRNA expression of IFN-γ and a 1.3-fold increase in mRNA expression of SOCS1 in the lean group compared to the obese group. mRNA expression of SOCS3 was similar in both groups. Conclusions: The level of IFN-γ increased at both transcriptional and translational levels, and mRNA expression of SOCS1 was higher in the lean group than in the obese group. The SOCS protein is a known negative regulator in insulin signaling pathways. Thus, our findings and available scientific literature suggest that IFN-γ might impair the insulin signaling pathway to a greater extent in lean patients than in obese patients via induction of SOCS1. This signaling pathway could be a major contributing factor to hyperglycemia in lean patients with T2DM compared with obese counterparts. This suggests that different therapeutic approaches to these groups might be of greater benefit in the treatment of T2DM.

Formulation Development of Topical Preparation Containing Nanoparticles of Povidone-Iodine for Wound Healing.

Povidone-iodine (PVI) is an antiseptic drug that is used for wound healing or for repair of the damaged tissue. Studies on solid lipid nanoparticles (SLNs) indicate that this system could potentially be used as a delivery system with improved drug entrapment efficiency and controlled drug release for hydrophilic actives. This study focuses on developing a topical gel containing SLNs of PVI for wound healing. SLNs were prepared by using the solvent emulsification diffusion method. Lipids such as glycerol monostearate, palmitic acid, and stearic acid, and surfactants such as polysorbate 80, soyalecithin, and Pluronic F-68 were used for the preparation of SLN. These were screened out based on particle size and entrapment efficiency of SLN. Gel was prepared by using Carbopol 940 (1% w/w) and propylene glycol (10% w/w). Formulated SLNs were evaluated by various in vitro and in vivo techniques. Based on the results, the drug-to-lipid ratio (1:3) and 2% polysorbate 80 (surfactant) along with stirring rate (3,000 rpm) produced the desired particle size (285.4 nm) with good stability. 22.85% drug loading and 88.83% drug entrapment efficiency were found in the optimized formulation. In vitro drug release shows that it follows the Korsmeyer-Peppas model. The animal study shows that the period of epithelization produced by the test group was 17.14 ± 1.35 days, which was near to that of the standard group (16.25 ± 1.24 days). Clinical Trial Registration number: 1044/PO/Re/S/07/CPCSEA.

Solid Lipid Nanoparticles Approach for Lymphatic Targeting Through Intraduodenal Delivery of Quetiapine Fumarate.

BACKGROUND: Lymphatic route is one of the prominent routes for improving the poor bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the bioavailability enhancement along with controlled and site specific drug delivery. OBJECTIVE: The aim of the present research work was to prepare and optimized the Quetiapine fumarate (an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal administration. METHOD: Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed using different lipids by Microemulsion technique and optimized by box behnken design. RESULTS: Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference (P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation. In vitro release data of optimized formulation (Q9) was subjected to zero order, first order and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal administration and several pharmacokinetic parameters were determined. AUC (0-∞) of optimized formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with that of drug suspension. CONCLUSION: On the basis of results of in vitro study, Q9 formulation was selected as optimized formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic delivery.

Formulation of Herbal Fast Disintegrating Tablets and its ex-vivo Study for Anti-histaminic Activity in Guinea Pig Ileum.

OBJECTIVE: The aim of present research work was to develop a herbal fast disintegrating tablet containing Fagonia schweinfurthii Hadidi dried extract and determining its antihistaminic activity using guinea pig ileum. METHOD: The tablets were formulated by wet granulation technique using three different superdisintegrants (croscarmillose, crospovidone and sodium starch glycolate) at three different levels. The tablets were evaluated for various physical properties like hardness, friability weight variation etc. and various mechanical properties like disintegration time, wetting time to select the best superdisintegrant. The selected superdisintegrant was further used as intra as well as extra granulating agent to develop fast disintegrating tablets of Fagonia schweinfurthii Hadidi dried extract. The optimized formulation was subjected to stability study as per the ICH guidelines. Finally, Ex-vivo antihistaminic study was conducted on guinea pig ileum for optimized formulation and compared with marketed tablet containing cetrizine HCl as API (Stanhist-10, Ranbaxy, Pvt. Ltd). RESULTS: Physical properties of all tablet batches were found to be acceptable and comply with various official specifications. The disintegration time and wetting time of optimized formulation (F'3) were found to be 1.15±0.08 and 0.56±0.04 min respectively. Results of Ex-vivo study showed a comparable histamine inhibition between optimized tablet (15%) and marketed tablet formulation (18.8%) in a dose of 5 µg/ml. CONCLUSION: On the basis of in-vitro and Ex-vivo studies, it was concluded that prepared herbal fast disintegrating tablets were stable and had potent antihistaminic activity.

Relationship of Serum Apolipoprotein A-V Levels, Oxidative Stress and Inflammatory Biomarkers with Hypertriglyceridemia in Type 2 Diabetes Mellitus.

BACKGROUND: Serum levels of triglycerides (TGs) are often found to be raised in type 2 diabetes mellitus (T2DM). TG levels ≥ 2.2 mM, systemic inflammation and oxidative stress (OS) are known to increase the risk of incident cardiovascular disease (CVD) substantially. In recent years, apolipoprotein A-V (Apo A-V protein) has attracted considerably as a modulator of circulating TG levels. OBJECTIVES: The study was conducted in order to evaluate the levels of Apo A - V proteins and markers of inflammation and OS in patients of T2DM with and without hypertriglyceridemia (HTG) and also to assess correlation between them. METHODS: T2DM patients were categorized into two groups of 40 participants, according to criteria for risk of CVD: group 1/ controls (TG ≤ 1.65 mM, n = 40) and group 2/ cases (TG ≥ 2.2 mM, n = 40). Despite the routine investigations, serum levels of Apo A-V, interleukin-6 (IL-6) and Insulin were estimated using ELISA, free fatty acids (FFA) with fluorometric assay and malondialdehyde (MDA) was measured using a spectrophotometer. Comparison of levels and correlation between variables was carried out with appropriate statistical tools. RESULTS: Serum Apo A-V protein levels were found significantly lower (P = 0.04) and MDA was significantly higher (P = 0.049) in cases. MDA correlated with TG levels positively (P = 0.000) and negatively with high density lipoproteins (HDL) (P = 0.000). However Apo A-V protein levels did not correlate with TG levels (P = 0.819, r = -0.027), IL-6 (r = 0.135, P = 0.269), FFA (r = 0.128, P = 0.277) and MDA (r = -0.217, P = 0.073). IL-6 levels significantly and positively correlated with HOMA-IR (r = 0.327, P = 0.004) in the all patients. CONCLUSIONS: In patients of T2DM, low levels of Apo A-V are associated with HTG, indicating that Apo A-V is linked with TG metabolism. Burden of oxidative stress is greater in HTG of T2DM as is evident from MDA levels and its correlation with TG levels. Since oxidative stress is an important patho-physiological basis which increases the risk of CVD in patients of T2DM with HTG. Further studies are required in order to explore the possible role of Apo A-V in TG metabolism in diabetes.

XRCC-1 Gene Polymorphism (Arg399Gln) and Susceptibility to Development of Lung Cancer in Cohort of North Indian Population: A Pilot Study.

BACKGROUND: Smoking has been considered to be the major cause of lung cancer. However, only a fraction of cigarette smokers develop this disease. This suggests the importance of genetic constitution in predicting the individual's susceptibility towards lung cancer. This genetic susceptibility may result from inherited polymorphisms in genes controlling carcinogen metabolism and repair of damaged deoxyribonucleic acid (DNA). These repair systems are fundamental to the maintenance of genomic integrity. X-ray repair cross complimenting group I (XRCC1), a major DNA repair gene in the base excision repair (BER) pathway. It is involved in repair by interacting with components of DNA at the site of damage. Inconsistent results have been reported regarding the associations between the Arg399Gln polymorphism of XRCC1. This study demonstrates the importance of recognition of this relationship of lung carcinoma and genetic constitution of the person which will help guide clinicians on the optimal screening of this disease. AIM: To assess the role of XRCC1 gene polymorphism (Arg399Gln) directly on the variation in susceptibility to development of lung cancer in North Indian subjects. MATERIALS AND METHODS: One hundred males with diagnosed cases of lung cancer were recruited from Delhi State Cancer Institute (DSCI). Hundred healthy volunteers were taken as controls. DNA isolation was done and Polymerase chain reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure undertaken to amplify the region containing Arg/Gln substitution at codon 399 (in exon 10). RESULTS: XRCC1 gene polymorphism is associated with increased risk of lung cancer when the Arg/Arg genotype was used as the reference group. The Arg/Gln and Gln/Gln was associated with statistically increased risk for cancer. CONCLUSION: Arg399Gln polymorphism in XRCC1 gene polymorphism is associated with lung cancer in North Indian subjects and screening for this polymorphism will help in targeting predisposed individuals and its prevention.

Exploring time of death from potassium, sodium, chloride, glucose & calcium analysis of postmortem synovial fluid in semi arid climate.

Estimation of time of death (TOD) with fair accuracy from postmortem changes still remains an important but difficult task to be performed by every autopsy surgeon under different climatic conditions. The environment plays an important role in the process of decomposition and thereby affecting the levels of electrolytes and other biochemical parameters in the postmortem samples. Since, there is limited information available on the levels of these biochemical parameters from semi arid environment, the present study was aimed to explore time of death by analyzing electrolyte, glucose and calcium levels of postmortem synovial fluid collected from samples under such climatic conditions. The synovial fluid samples from two hundred and ten bodies brought to University College of Medical Sciences and associated Guru Teg Bahadur Hospital Delhi for medico-legal postmortem examination, during the period of November 2010 to April 2012, were analyzed for potassium, sodium, chloride, glucose and calcium. Univariate regression analysis of electrolyte concentrations of synovial fluid showed significant positive relationship between time of death and potassium (r = 0.840, p = 0.000). However, there was negative relationship between time of death and sodium (r = -0.175, p = 0.011) & glucose (r = -0.427, p = 0.000) and no significant relationship was found between time of death and calcium (r = 0.099, p = 0.152) & chloride (r = 0.082, p = 0.24) among the samples analyzed.

Osmotically regulated two-compartment asymmetric membrane capsules for simultaneous controlled release of anti-hypertensive drugs.

In the present study, asymmetric membrane capsules (AMCs) with two compartments were successfully developed for simultaneous delivery of two poorly water-soluble drugs, Atenolol and Amlodipine Besylate, by using solubility modulation approach. Scanning electron microscopy (SEM) before dissolution showed presence of outer dense region and inner porous region for the prepared asymmetric membrane and the pore size increased after dissolution for both outer and inner layer. Diffuse reflectance spectroscopy (DRS) showed no incompatibility between the drug(s) and the excipients used in the study. The developed system was able to control the release of ATN and AMB by increasing the solubility through buffering agents of different strengths (0.25N to 1.0N). As the level of buffering agent was increased, the solubility of drugs also increased inside the asymmetric membrane capsule. The developed system was independent of the agitation intensity of the dissolution fluid but was dependent on the polymer diffusibility and osmotic pressure of the media, which clearly stated that osmotic pumping was the primary mechanism of drug(s) release from AMCs. The results of in-vitro demonstration of effect of membrane thickness on dissolution fluid entering AMCs showed that as the membrane thickness increased the volume of dissolution fluid entering into AMC decreased. The release kinetic studies of different formulations of AMCs showed that formulation code six, which consists of the highest amount of osmotic agents and optimum amount of buffering agents, was the best formulation, and it followed zero order release kinetics (r(2)=0.9990 for ATN and r(2)=0.9988 for AMB).