A novel rosuvastatin calcium cow ghee fraction biform complex: formulation characterization and evaluation

2021 ◽  
Vol 11 ◽  
Author(s):  
Vijendra Kumar Suryawanshi ◽  
Khomendra Kumar Sarwa ◽  
Suhas Narayan Sakarkar ◽  
Chanchal Deep Kaur
Keyword(s):  
Fatty Acids ◽  
Oral Bioavailability ◽  
Ex Vivo ◽  
Fatty Acid Content ◽  
Lipid Lowering ◽  
Thermal Fractionation ◽  
Ex Vivo Permeation ◽  
Anti Inflammatory ◽  
Rosuvastatin Calcium

Background: Rosuvastatin calcium is a statin class of drug having limited oral bioavailability of about 20%. This problem might be overcome by making the biform complex using cow ghee fraction as a bioavailability enhancer. Methods: A precise thermal fractionation technique was adopted to separate different fatty acids from cow ghee. Collected fractions were subjected to characterization over parameters reported for fatty acids. LC-MS and FTIR confirm the content variation in the collected fraction. Biform complex was prepared by fusion method with a constant ratio of drug and cow ghee fraction. The prepared complex was subjected to FTIR, DSC, and LC-MS study to confirm chemical composition characteristics. Drug content, in-vitro and ex-vivo permeation studies were also performed. The anti-inflammatory response was measured using the carrageenan paw-induced edema rat model. Lipid-lowering effect and inflammation marker analysis was also performed using ELISA specific kit. Results: The biform complex prepared with a thermal fraction at 30ºC of cow ghee show the highest in-vitro and ex-vivo permeation. The anti-inflammation response of the biform complex F1 was higher than other tested formulations with considerable lipid and lipoprotein lowering properties. Conclusions: This study confirms that the thermal fractionation method abled to separate cow ghee as per their fatty acid content. The complexion of rosuvastatin calcium with cow ghee thermal fraction enhances oral bioavailability followed by the anti-inflammatory and lipid-lowering activity.

scholarly journals Crucial role of fatty acid oxidation in asthmatic bronchial smooth muscle remodelling

2021 ◽  
pp. 2004252
Author(s):  
Pauline Esteves ◽  
Landry Blanc ◽  
Alexis Celle ◽  
Isabelle Dupin ◽  
Elise Maurat ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Fatty Acid ◽  
Ex Vivo ◽  
Fatty Acid Content ◽  
Ldl Receptor ◽  
Beta Oxidation ◽  
Bronchial Smooth Muscle

BackgroundBronchial smooth muscle (BSM) remodelling in asthma is related to an increased mitochondrial biogenesis and enhanced BSM cell proliferation in asthma. Since (i) mitochondria produce the highest levels of cellular energy and (ii) fatty acid beta-oxidation is the most powerful way to produce ATP, we hypothesized that, in asthmatic BSM cells, energetic metabolism is shifted towards the beta-oxidation of fatty acids.ObjectivesWe aimed to characterize BSM cell metabolism in asthma both in vitro and ex vivo to identify a novel target for reducing BSM cell proliferation.MethodsTwenty-one asthmatic and 31 non-asthmatic patients were enrolled. We used metabolomic and proteomic approaches to study BSM cells. Oxidative stress, ATP synthesis, fatty acid endocytosis, metabolite production, metabolic capabilities, mitochondrial networks, cell proliferation and apoptosis were assessed on BSM cells. Fatty acid content was assessed in vivo using MALDI-spectrometry imaging.ResultsAsthmatic BSM cells were characterized by an increased rate of mitochondrial respiration with a stimulated ATP production and mitochondrial β-oxidation. Fatty acid consumption was increased in asthmatic BSM both in vitro and ex vivo. Proteome remodelling of asthmatic BSM occurred via 2 canonical mitochondrial pathways. The levels of CPT2 and LDL-receptor, which internalize fatty acids through mitochondrial and cell membranes, respectively, were both increased in asthmatic BSM cells. Blocking CPT2 or LDL-receptor drastically and specifically reduced asthmatic BSM cell proliferation.ConclusionThis study demonstrates a metabolic switch towards mitochondrial beta-oxidation in asthmatic BSM and identifies fatty acid metabolism as a new key target to reduce BSM remodelling in asthma.

ROSUVASTATIN CALCIUM PRONIOSOME POWDER: A NOVEL APPROACH TO IMPROVE INTESTINAL ABSORPTION AND BIOAVAILABILITY

2020 ◽  
pp. 148-156
Author(s):  
SMITHA GANDRA
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Ionic Surfactant ◽  
Bioavailability Enhancement ◽  
Rosuvastatin Calcium

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of rosuvastatin calcium by improving solubility, dissolution, and/or intestinal permeability. Methods: Proniosomal powder formulations were prepared with rosuvastatin calcium drug varying the Span 40 and cholesterol ratio in the range of 0.8:0.2–0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug:Span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study, and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies. Results: Physicochemical studies help in optimization of formulations. Enhancement in dissolution is due to incorporation of rosuvastatin calcium into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Conclusion: Proniosomes provide a powerful and functional way of distribution of inadequately soluble rosuvastatin calcium drug which is proved from in vivo studies based on the enhanced oral delivery.

Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

2020 ◽  
Vol 13 (6) ◽  
pp. 5250-5255
Author(s):  
Ashwin Kumar Tulasi ◽  
Anil Goud Kandhula ◽  
Ravi Krishna Velupula
Keyword(s):  
Particle Size ◽  
Nasal Mucosa ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Chemical Properties ◽  
Brain Targeting ◽  
Oral Tablet ◽  
Promising Alternative ◽  
Ex Vivo Permeation

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was   88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

2020 ◽  
Vol 10 ◽  
Author(s):  
Divya Thakur ◽  
Gurpreet Kaur ◽  
Sheetu Wadhwa ◽  
Ashana Puri
Keyword(s):  
Ex Vivo ◽  
Clinical Investigation ◽  
In Vivo Studies ◽  
Tween 20 ◽  
Inflammatory Disorders ◽  
Rat Paw Edema ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

scholarly journals Efficacy of Posidonia oceanica Extract against Inflammatory Pain: In Vivo Studies in Mice

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 48
Author(s):  
Laura Micheli ◽  
Marzia Vasarri ◽  
Emanuela Barletta ◽  
Elena Lucarini ◽  
Carla Ghelardini ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Ex Vivo ◽  
Antioxidant Properties ◽  
Posidonia Oceanica ◽  
In Vivo Studies ◽  
Myeloperoxidase Activity ◽  
Intraplantar Injection ◽  
Hot Plate Test ◽  
Anti Inflammatory

Posidonia oceanica (L.) Delile is traditionally used for its beneficial properties. Recently, promising antioxidant and anti-inflammatory biological properties emerged through studying the in vitro activity of the ethanolic leaves extract (POE). The present study aims to investigate the anti-inflammatory and analgesic role of POE in mice. Inflammatory pain was modeled in CD-1 mice by the intraplantar injection of carrageenan, interleukin IL-1β and formalin. Pain threshold was measured by von Frey and paw pressure tests. Nociceptive pain was studied by the hot-plate test. POE (10–100 mg kg−1) was administered per os. The paw soft tissue of carrageenan-treated animals was analyzed to measure anti-inflammatory and antioxidant effects. POE exerted a dose-dependent, acute anti-inflammatory effect able to counteract carrageenan-induced pain and paw oedema. Similar anti-hyperalgesic and anti-allodynic results were obtained when inflammation was induced by IL-1β. In the formalin test, the pre-treatment with POE significantly reduced the nocifensive behavior. Moreover, POE was able to evoke an analgesic effect in naïve animals. Ex vivo, POE reduced the myeloperoxidase activity as well as TNF-α and IL-1β levels; further antioxidant properties were highlighted as a reduction in NO concentration. POE is the candidate for a new valid strategy against inflammation and pain.

scholarly journals FORMULATION OF RIZATRIPTAN BENZOATE SUBLINGUAL TABLETS PREPARED BY DIRECT COMPRESSION WITH DIFFERENT BIOADHESIVE POLYMER: IN VITRO AND EX VIVO EVALUATION

2017 ◽  
Vol 10 (16) ◽  
pp. 36
Author(s):  
Harmanpreet Singh ◽  
Pooja Jaiswal ◽  
Suksham Gupta ◽  
Simerjit Singh
Keyword(s):  
Ex Vivo ◽  
Methyl Cellulose ◽  
Systemic Circulation ◽  
Direct Compression ◽  
Compression Process ◽  
Rizatriptan Benzoate ◽  
Dissolution Tests ◽  
Ex Vivo Permeation ◽  
Bioadhesive Polymers

  Objective: The current investigation deals with formulation and evaluation of fast disintegrating sublingual tablets of rizatriptan benzoate (RTB) to produce its intended therapeutic effect for acute treatment of migraine. When the drug is given by sublingual route, it overcomes the first pass metabolism and quick entry of drug in systemic circulation is obtained. It would result in fast pharmacological response hence faster relief from migraine which is an important criterion in migraine therapy.Methods: In this study, RTB sublingual tablets were prepared using direct compression process using various bioadhesive polymers such as sodium carboxymethyl cellulose, hydroxyl propyl methyl cellulose-K4M, and chitosan at various concentration ranging 0.5-5% w/w along with sodium starch glycolate (SSG) or cross carmellose sodium (CCS) as super disintegrants at different concentration ranging 2-8% w/w.Results: The tablets disintegrated quickly and dissolution tests conclude that RTB was released from the formulation within the compendial limits. The formulations batches (A8 and B8) containing 2% w/w chitosan along with 2% w/w SSG or CCS which disintegrate rapidly and show high dissolution and ex vivo permeation were selected as optimized formulations.Conclusion: The results obtained from the study showed that the bioavailability problem of the drug has been solved as the drug is given by sublingual route and it directly enters into systemic circulation. Furthermore, the formulation overcomes the problems associated with migraine attack as fast disintegrating technology is used.

scholarly journals Olive Oil Based Organogels for Effective Topical Delivery of Fluconazole: In-vitro Antifungal Study

2020 ◽  
pp. 29-36
Author(s):  
Mohammad Muqtader Ahmed ◽  
Farhat Fatima ◽  
Abdul Bari Mohammed
Keyword(s):  
Olive Oil ◽  
Ex Vivo ◽  
Similarity Index ◽  
Ex Vivo Permeation ◽  
Efficient Delivery ◽  
In Vitro Diffusion ◽  
Permeation Studies ◽  
The Stability ◽  
Hot Melt

The objective of the study was to formulate olive oil based organogels for the topical application of fluconazole (FLZ), to ensure the efficient delivery of the drug deeper in to the skin layers. Methods: Nine formulations developed by hot-melt method using olive oil, sorbitan monostearate (SMS) and FLZ. Prepared formulations characterized for macro evaluations, pH, spreadibility, viscosity, gel-sol transition, in-vitro diffusion study. Further optimized formulation evaluated for ex-vivo percutaneous permeation, in-vitro antifungal studies and stability studies by similarity index. Results: The results of evaluated parameters ensure the stability and effectiveness of the prepared olive oil based organogels. In-vitro diffusion studied reflects decrease in drug release with increase in surfactant concentration due to increase in viscosity. Moreover, ex-vivo permeation studies revealed that the permeation of FLZ was enhanced for optimized formulations (F6) as compared to the marketed gel formulation. Further, the optimized formulation exhibits the broad zone of inhibition against fungal strains in comparison to control and marketed product during in-vitro antifungal study. Conclusion: The olive oil based organogels formulation shown the enhanced permeation of FLZ from organogel network structure with good antifungal activity as compared to the marketed formulation. Henceforth, the FLZ organogel formulations could be used topically for the effective treatment of fungal infection.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

scholarly journals Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Hsin-Ling Yang ◽  
Ting-Yu Yang ◽  
Yugandhar Vudhya Gowrisankar ◽  
Chun-Huei Liao ◽  
Jiunn-Wang Liao ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Ex Vivo ◽  
Root Extract ◽  
Piper Methysticum ◽  
Serum Lipase ◽  
Antioxidant Genes ◽  
Anti Inflammatory

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

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