Objective: To statistically design, optimize and evaluate a liquid oral, floating in situ gel of metformin hydrochloride (MH) to increase the gastric residence time (the absorption window being the upper part of the duodenum), sustain and modulate the release behavior of the drug. No liquid oral SR formulations of MH are yet available in the market. Methods: A simple mixing based ionic cross-linking method was used for the formulation. A Two-square Factorial Design was employed and the effect of sodium alginate and three categorical levels of HPMC (K4M, K100M, E50) on the response variables were studied. Results: The optimized formulation gelled instantaneously in simulated gastric fluid and showed>24 h floating. The drug release in 1h was 37.98 %, followed by a moderate sustained release for 12 h. Pharmacodynamic studies showed a significant reduction in blood glucose levels in Wistar rats. Short term preclinical safety studies revealed no toxicity to pancreatic tissues. On the contrary, faster regeneration of the β cells of the islets of Langerhans was observed with the group treated with the optimized formulation. Stability studies revealed a 2-year shelf life. Conclusion: An elegant, needle-free, in situ gelling, SR liquid oral of metformin hydrochloride could be developed with drug release modulated as per official specifications for SR formulations of MH. This would be an interesting alternative for geriatric patients who find it difficult to swallow bulky tablets.

ObjectivesThe main objective of the present study is to evaluate the mitigative effect of hydroalcoholic extract of Momordica cymbalaria fruits against sodium fluoride (NaF) induced hepatotoxicity.MethodsIn this study, Wistar male albino rats were randomly divided into five groups of six rats each. Group I and II served as normal and toxic controls. Group III as plant control received extract at a dose of 400 mg/kg b. wt, p.o and Groups IV and V as treatment groups received extract at a dose 200 and 400 mg/kg b. wt, p.o for 30 days. All groups except Groups I and III received 100 ppm of NaF through drinking water. After completion of the study, blood collected for the estimation of liver blood serum biomarkers such as aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline Phosphatase (ALP), direct and total bilirubin, total protein and albumin. The liver tissue homogenate was for estimation of lipid peroxidation, catalase, and reduced glutathione levels.ResultsThe results showed that NaF intoxication caused elevation of liver blood serum levels and lipid peroxidation; decreased levels of serum total protein, albumin and liver reduced glutathione, and catalase observed. The treatment groups showed decreased elevated serum biomarkers (ALT, AST, and ALP), liver lipid peroxidation and increased serum total protein and albumin, liver reduced glutathione and catalase levels in a dose-dependent manner. Histopathological studies also further strongly supported for mitigative effects of the plant.ConclusionsIn conclusion, our findings of the study indicated that M. cymbalaria fruits were a potential drug candidate in the treatment of NaF induced hepatotoxicity.

Background: Excessive angiogenesis can be the root cause of many pathological conditions. Various types of ion channels are found on the endothelial cells. These ion channels play a vital role in the multi-stepped process of angiogenesis. The study aims to investigate the anti-angiogenic effects of specific ion channel modulators mefloquine (volume-regulated chloride channel blocker), lubiprostone (ClC-2 channel agonist), and 4-aminopyridine (voltage-gated potassium channel blocker). Results: The anti-angiogenic activity of ion channel modulators was screened by measuring its effects on the area of neovascularization and histopathological studies by in vivo (corneal neovascularization) method and by in vitro assays, endothelial cell proliferation assay, cell migration assay, and matrigel cord-like morphogenesis assay. The test and standard drug (bevacizumab) groups were compared with the control group using one-way ANOVA, followed by post hoc test, and Dunnett's test to compare the mean of all the groups with the control mean. The results revealed that mefloquine at the dose of 0.6% w/v and 1.0% w/v, lubiprostone at the dose of 0.5% w/v and 1.0% w/ v, and 4-aminopyridine at the dose of 2% w/v and 4% w/v showed significant anti-angiogenic property. In the studies on human umbilical vein endothelial cells, the test drugs (100 nM) showed significant inhibition of proliferation, migration, and decrease in network length of cord-like tubes. Conclusion: The scientific findings indicate that the test drugs have potent anti-angiogenic activity by inhibiting the cell proliferation, inhibiting the cell volume increase, arresting the cell cycle progression and by causing membrane hyperpolarization. The potent anti-angiogenic drugs obtained by repurposing these ion channel modulators, in the further studies, will be able to treat the diseases due to excess angiogenesis from the root cause.

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Diklofenak sınırlı çözünürlük, düşük biyoabsorpsiyon ve gastrik toksisite gösterir. Çalışmanın amacı, yukarıdaki kısıtlamaları ele almak ve RA'nın kronoterapisi için çok birimli bir formülasyon tasarlamaktır. Gereç ve Yöntemler: DC, SSG ve GG ile katı dispersiyonları hazırlandı. Aynı boyutlu (∼400 µm) nonpareil çekirdekler, hemen salım yapan pelletler (DMP-1 ve DMP-2) ve kontrollü salımlı pelletler (DMP-3 ve DMP-4) üretmek için katı dispersiyonlarla kaplandı. Elde edilen kontrollü salım pelletleri, pulsatil salım pelletleri (DMPP) elde etmek için metakrilat polimerleri ile daha da katmanlı hale getirildi. DMPP için çözünürlük, FTIR, DSC, mikrometrik, SEM, etkin madde içeriği, etkin madde salımı, farmakokinetik ve stabilite çalışmaları yapıldı. Bulgular: DC'nin çözünürlüğü, katı dispersiyonlardaki hidrofilik taşıyıcıların varlığına bağlı olarak 164 kat arttı. FTIR spektrumunda ve termogramlarda kimyasal ve fiziksel etkileşimler gözlemlenmedi. Akışkanlaştıran yataklı işlemci, 19.5 dereceden daha az bir akış açısı ve %95.18 ile %98.87 arasında DC içeriği olan yüksek kaliteli, yuvarlak ve düzenli pelletlerin üretimini kolaylaştırdı. Maksimum etkin madde 12 saat sonunda DMPP'den salındı. Objectives: Diclofenac exhibits limited solubility, low bioabsorption and gastric toxicity. The objective of the study was to address the above limitations and to design a multi-particulate formulation for the chronotherapy of RA. Materials and Methods: Solid dispersions of DC with SSG and GG were prepared. Uniform-sized (∼400 µm) non-pareil seeds were coated with solid dispersions to produce immediate-release pellets (DMP-1 and DMP-2) and controlled-release pellets (DMP-3 and DMP-4). The resultant controlled-release pellets were further layered with methacrylate polymers to obtain pulsatile-release pellets (DMPP). Solubility, FTIR, DSC, micrometrics, SEM, drug content, drug release, pharmacokinetics, and stability studies were performed for DMPP. Results: The solubility of DC was improved by 164-folds due to the presence of hydrophilic carriers in the solid dispersions. No chemical and physical interactions were noticed in FTIR spectra and also in thermograms. A fluidized bed processor facilitated the production of high-quality, circular, and regular pellets with an angle of repose less than 19.5 degrees and DC content between 95.18% and 98.87%. The maximum drug was released from DMPP at the end of 12 hours. DMP-1 and DMP-2 pellets had 2 hr of drug release and pulsatile, controlled-release pellets had a 6 hr lag phase followed by 12 hr controlled release. Both DMP-1 and DMP-2-immediate showed first-order release followed by Hixson-Crowell kinetics, whereas DMPP pellets followed zero-order release with Higuchi's kinetics. The maximum concentration of DC in plasma was 400.8 ng/mL at 5 hr for DMP-2 and 381.1 ng/mL at 14 hr for DMPP-5. The solubility of DC was increased with the application of solid dispersion and in turn increased the pharmacokinetics. The pellets were plausibly stable over a period of 90 days. Conclusion: Thus, multi-p...