FORMULATION AND OPTIMIZATION OF RITONAVIR NASAL NANOSUSPENSION FOR BRAIN TARGETING

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (4) ◽  
pp. 28-41
Author(s):  
Tapasya R. Mulam ◽  
Sanjay J. Kshirsagar ◽  
Smita P. Kakad ◽  
Keyword(s):  
Enzyme Inhibitor ◽  
Ex Vivo ◽  
Hepatic Metabolism ◽  
Oral Route ◽  
Brain Targeting ◽  
Onset Of Action ◽  
Protease Enzyme ◽  
The Central Nervous System ◽  
Ex Vivo Permeation Study

Nowadays, HIV associated neurological disorder especially HIV-1 virus infection is enhanced. Current available HIV therapies only reduce the plasma viral level and do not kill the virus completely. Administered dosage form does not reach the central nervous system (CNS) completely by the conventional approach. The oral route of drug administration,causes gastrointestinal irritation, hepatic metabolism and slow onset of action and some methods are invasive, resulting in the patient's non compliance. To overcome these problems, an effective novel formulation that will directly reach the CNS or brain needs to be developed.This study aims to formulate intranasal nanosuspension of ritonavir. Ritonavir is widely used as an antiretroviral agent and it is a protease enzyme inhibitor which is poorly soluble in water. High pressure homogenization technique was used for preparation prepare and optimization of nanosuspension by using 2 factors 3 level full factorial design, which is further characterized for particle size, polydispersity index, zeta potential, pH, drug content, in vitro drug diffusion and ex vivo permeation study. For stability of nanosuspension, lyophilization of optimized formulation was done. A comparison study between plain drug, nanosuspension and the lyophilized formulation was carried out, and it showed a significant increase in drug release from the membrane.

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.

FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILMS OF PROCHLORPERAZINE MALEATE

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (12) ◽  
pp. 23-33
Author(s):  
R. Kanekar ◽  
◽  
P. M. Dandagi ◽  
A. P. Gadad
Keyword(s):  
Ex Vivo ◽  
Rapid Onset ◽  
Drug Release Profile ◽  
Onset Of Action ◽  
In Vitro Drug Release ◽  
Physico Chemical ◽  
Film Forming ◽  
Oral Films ◽  
Ex Vivo Study

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.

scholarly journals Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

2020 ◽  
Vol 21 (10) ◽  
pp. 3631 ◽  
Author(s):  
Raffaella Boggia ◽  
Federica Turrini ◽  
Alessandra Roggeri ◽  
Guendalina Olivero ◽  
Francesca Cisani ◽  
...  
Keyword(s):  
Oral Administration ◽  
Ellagic Acid ◽  
Ex Vivo ◽  
Behavioral Skills ◽  
Aged Mice ◽  
Age Related ◽  
The Central Nervous System ◽  
The Impact ◽  
Old Mice

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.

scholarly journals Sensory Stimuli Directly Acting at the Central Nervous System Regulate Gastric Ghrelin Secretion. An ex Vivo Organ Culture Study

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3998-4006 ◽  
Author(s):  
Luisa M. Seoane ◽  
Omar Al-Massadi ◽  
J. Eduardo Caminos ◽  
Sulay A. Tovar ◽  
Carlos Dieguez ◽  
...  
Keyword(s):  
Organ Culture ◽  
Ex Vivo ◽  
Negative Energy ◽  
Gastrointestinal Hormone ◽  
Suitable Model ◽  
Sensory Stimuli ◽  
Orexigenic Peptide ◽  
The Central Nervous System ◽  
Ghrelin Secretion

Ghrelin, a novel gastrointestinal hormone involved in GH regulation, has been postulated as a relevant orexigenic peptide released by splanchnic tissues. Descriptive studies have shown that plasma ghrelin levels increase in states of negative energy balance or fasting, while decreasing in obesity and after feeding. In the present study, a novel organ-culture model of gastric tissue explants obtained from rat donors has been validated for ex vivo experiments. Fasting induced gastric ghrelin release as well as ghrelin mRNA expression that were reflected in plasma. Interestingly, those changes were fully reverted by 15 min of refeeding before stomach extraction. Unexpectedly, when animals were allowed 15 min before explant extraction to see or smell, but not eat, the food (tease feeding), ghrelin secretion was suppressed just like in gastric explants from refed animals. This effect was blocked when the animals were subjected to surgical vagotomy or treated with atropine sulphate. In conclusion, gastric explants were a suitable model for testing ghrelin mechanism of secretion in vitro, and they were found to maintain memory of the previously received signals. Similar to feeding, tease feeding resulted in suppression of ghrelin discharge by explants.

Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism

2020 ◽  
Author(s):  
Valentina S. Klaus ◽  
Sonja C. Schriever ◽  
Andreas Peter ◽  
José Manuel Monroy Kuhn ◽  
Martin Irmler ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Hepatic Metabolism ◽  
Omics Data ◽  
Network Integration ◽  
Data Set ◽  
Metabolomics Data ◽  
Different Types ◽  
Hepatic Fat ◽  
Liver Biopsies

ABSTRACTThe steadily increasing amount of newly generated omics data of various types from genomics to metabolomics is a chance and a challenge to systems biology. To fully use its potential, one key is the meaningful integration of different types of omics. We here present a fully unsupervised and versatile correlation-based method, termed Correlation guided Network Integration (CoNI), to integrate multi-omics data into a hypergraph structure that allows for identification of effective regulators. Our approach further unravels single transcripts mapped to specific densely connected metabolic sub-graphs or pathways. By applying our method on transcriptomics and metabolomics data from murine livers under standard chow or high-fat-diet, we isolated eleven genes with a regulatory effect on hepatic metabolism. Subsequent in vitro and ex vivo experiments in human liver cells and human obtained liver biopsies validated seven candidates including INHBE and COBLL1, to alter lipid metabolism and to correlate with diabetes related traits such as overweight, hepatic fat content and insulin resistance (HOMA-IR). Last, we successfully applied our methods to an independent data-set to confirm its versatile and transferable character.

scholarly journals Formulation and Evaluation of Tacrolimus Transdermal Gel

2019 ◽  
Vol 9 (6-s) ◽  
pp. 110-118
Author(s):  
CH. Suryakumari ◽  
M. Narender ◽  
K. Umasankar ◽  
Siva Prasad Panda ◽  
S.N. Koteswara Rao ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Release Kinetics ◽  
In Vitro Drug Release ◽  
Surface Ph ◽  
Abdominal Skin ◽  
Ex Vivo Permeation ◽  
Ex Vivo Permeation Study ◽  
Carbopol 934P

The present investigation is concerned with formulation and evaluation of Transdermal gels of Tacrolimus, anti-psoriasis drug, to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. Twelve formulations were developed with varying concentrations of polymers like Carbopol 934P, HPMCK4M and Sodium CMC. The gels were tested for clarity, Homogeneity, Spreadability, Extrudability, Viscosity, surface pH, drug Content uniformity, in-vitro drug diffusion study and ex-vivo permeation study using rat abdominal skin. FTIR studies showed no evidence on interactions between drug, polymers and excipients. The best in-vitro drug release profile was achieved with the formulation F4 containing 0.5 mg of exhibited 6 hr drug release i.e. 98.68 % with desired therapeutic concentration which contains the drug and Carbopol 934p in the ratio of 1:2. The surface pH, drug content and viscosity of the formulation F4 was found to be 6.27, 101.3% and 3, 10,000cps respectively. The drug permeation from formulation F4 was slow and steady and 0.89gm of tacrolimus could permeate through the rat abdominal skin membrane with a flux of 0.071 gm hr-1 cm-2. The in-vitro release kinetics studies reveal that all formulations fit well with zero order kinetics followed by non-Fickian diffusion mechanism. Keywords: Transdermal gel, Viscosity, In-vitro drug release, In-vitro drug release kinetics study, Ex-vivo permeation study

scholarly journals FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILM OF ANTI-ALLERGIC DRUG

2018 ◽  
Vol 6 (3) ◽  
pp. 5-16 ◽  
Author(s):  
ABRAHAM LINKU ◽  
JOSEPH SIJIMOL
Keyword(s):  
Ex Vivo ◽  
Methyl Cellulose ◽  
Moisture Loss ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Onset Of Action ◽  
Disintegration Time ◽  
Permeation Study ◽  
Weight Variation

The aim of present work was the development of fast dissolving oral film of Loratadine to overcome the limitations of current routes of administration, to provide immediate action and increase the patient compliance. To improve the bioavailability of the drug, fast dissolving oral film were formulated using different grades of Hydroxy Propyl Methyl Cellulose(HPMC) and various plasticizers like Polyethylene Glycol(PEG) 400, glycerol, Propylene glycol(PG) by solvent casting method. The formulated films were evaluated for film thickness, surface pH, folding endurance, weight variation, % moisture loss, exvivo permeation study, tensile strength, % elongation, drug content uniformity, in vitro dissolution studies,in vitro disintegration test and in vivo study. The optimized formulation (F9) containing HPMC E5 and glycerol showed minimum disintegration time (10.5 s), highest in vitrodissolution (92.5%) and satisfactory stability. Ex vivo permeation study of optimized formulation showed a drug release of 80.6% within 10 min. The milk induced leucocytosis inrat proved that fast dissolving oral films of Loratadine produced a faster onset of action compared to the conventional tablets. These findings suggest that fast dissolving oral film of Loratadine could be potentially useful for treatment of allergy where quick onset of action is required.

scholarly journals Cannabinoid WIN 55,212-2 Inhibits Human Glioma Cell Growth by Triggering ROS-Mediated Signal Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kun Wang ◽  
Qian Wang ◽  
Qinghao Li ◽  
Zhaoqiang Zhang ◽  
Jing Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Ex Vivo ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Human Glioma ◽  
U251 Cell ◽  
The Central Nervous System

Glioblastoma is a highly invasive primary malignant tumor of the central nervous system. Cannabinoid analogue WIN 55,212-2 (WIN) exhibited a novel anticancer effect against human tumors. However, the anticancer potential and underlying mechanism of WIN against human glioma remain unclear. Herein, the anticancer efficiency and mechanism of WIN in U251 human glioma cells were investigated. The results showed that WIN dose-dependently inhibited U251 cell proliferation, migration, and invasion in vitro. WIN treatment also effectively suppressed U251 tumor spheroids growth ex vivo. Further studies found that WIN induced significant apoptosis as convinced by the caspase-3 activation and release of cytochrome C. Mechanism investigation revealed that WIN triggered ROS-mediated DNA damage and caused dysfunction of VEGF-AKT/FAK signal axis. However, ROS inhibition effectively attenuated WIN-induced DNA damage and dysfunction of VEGF-AKT/FAK signal axis and eventually improved U251 cell proliferation, migration, and invasion. Taken together, our findings validated that WIN had the potential to inhibit U251 cell proliferation, migration, and invasion and induce apoptosis by triggering ROS-dependent DNA damage and dysfunction of VEGF-AKT/FAK signal axis.

scholarly journals Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

1994 ◽  
Vol 5 (5) ◽  
pp. 304-311 ◽  
Author(s):  
K. J. Doshi ◽  
F. D. Boudinot ◽  
J. M. Gallo ◽  
R. F. Schinazi ◽  
C. K. Chu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Brain Targeting ◽  
The Central Nervous System ◽  
Intravenous And Oral Administration ◽  
The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

scholarly journals Sublingual Delivery of Frovatriptan: An Indication of Potential Alternative Route

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Hitesh Verma ◽  
Surajpal Verma ◽  
Shyam Baboo Prasad ◽  
Harmanpreet Singh
Keyword(s):  
Migraine Attack ◽  
Ex Vivo ◽  
Acute Migraine ◽  
Onset Of Action ◽  
Permeation Studies ◽  
Potential Alternative ◽  
Histopathological Studies ◽  
Sublingual Delivery ◽  
Acute Migraine Attack

Frovatriptan, a 5-HT1B and 5-HT1D receptor agonist, is used for the treatment of acute migraine attack. This molecule is classified into second line therapy because of its slow onset of action (peak response obtained after 4 hours of administration) and low bioavailability (25%). Moreover, its therapy is the most costly among all triptans. Attempt has been made in present work to suggest a way out to fasten its onset of action and to enhance its bioavailability. Prepared tablets were evaluated by physicochemical tests, in vitro permeation studies, ex vivo permeation studies, and histopathological studies. Suitable mathematical calculations were performed to calculate the minimum amount of bioavailability that could be enhanced. Tablets containing chitosan (5% w/w) were found to give optimum results. Prepared tablets can double the bioavailability of frovatriptan and can initiate its response within 10 minutes of its administration. Suggestive alternative has the potential to increase the efficacy of frovatriptan for treating acute migraine attack.

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