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.

scholarly journals FORMULATION AND EVALUATION OF OPTIMISED MALTODEXTRIN BASED PRONIOSOME POWDERS CONTAINING BAZEDOXIFENE ACETATE FOR ORAL DELIVERY

2020 ◽  
pp. 56-66
Author(s):  
SMITHA GANDRA
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Ionic Surfactant ◽  
Bioavailability Enhancement ◽  
Cholesterol Ratio

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and/or intestinal permeability. Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 40 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as a 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: Physico-chemical studies help in the optimization of formulations. Enhancement in dissolution is due to the incorporation of bazedoxifene acetate 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 the gastrointestinal membrane compared to control. Conclusion: In conclusion, proniosomes provide a powerful and functional way of the distribution of inadequately soluble bazedoxifene acetate drug, which is proved from in vivo studies based on the enhanced oral delivery.

scholarly journals ENHANCED INTESTINAL ABSORPTION AND BIOAVAILABILITY VIA PRONIOSOMES FOR BAZEDOXIFENE ACETATE DRUG

2020 ◽  
pp. 31-42
Author(s):  
SMITHA GANDRA
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Ex Vivo ◽  
Angle Of Repose ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Ionic Surfactant ◽  
Enhanced Absorption ◽  
Span 60

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and intestinal permeability. Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 60 and cholesterol ratio in the range of 0.8:0.2 to 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 60 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: Physico-chemical studies among various formulations helped in optimization of batch. Good flow properties confirmed from angle of repose values indicate easy filling into capsules. Enhancement in dissolution is due to incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Solid state characterization studies prove the transformation to amorphous form with small particle size improving permeation. No drug excipient interaction was observed and sample is stable in refrigerated conditions. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Invivo studies proved enhanced absorption of bazedoxifene acetate drug by oral route. Conclusion: In conclusion, proniosomes provide a powerful and functional way of distribution of inadequately soluble bazedoxifene acetate drug which is proved from in vivo studies based on the enhanced oral delivery.

Biopharmaceutical and Preclinical Studies of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants for Oral Delivery

1970 ◽  
Vol 9 (1) ◽  
pp. 3102-3111
Author(s):  
Narendar Dudhipala ◽  
Arjun Narala ◽  
Dinesh Suram ◽  
Karthik Yadav Janga
Keyword(s):  
Oral Delivery ◽  
Molecular State ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Phase Solubility ◽  
Microscopic Studies ◽  
Pure Drug

The objective of this present study is to develop a semisolid dispersion (SSD) of zaleplon with the aid of self-emulsifying lipid based amphiphilic carriers (TPGS E or Gelucire 44/14) addressing the poor solubility of this drug. A linear relationship between the solubility of drug with respect to increase in the concentration of lipid surfactant in aqueous medium resulting in AL type phase diagram was observed from phase solubility studies. Fusion method was employed to obtain semisolid dispersions (SSD) of zaleplon which showed high content uniformity of drug. The absence of chemical interactions between the pure drug, excipients and formulations were conferred by Fourier transmission infrared spectroscopic examinations. The photographic images from polarized optical microscopic studies revealed the change in crystalline form of drug to amorphous or molecular state. The superior dissolution parameters of zaleplon from SSD over pure crystalline drug interpreted from in vitro dissolution studies envisage the ability of these lipid surfactants as solubility enhancers. Further, the caliber of TPGS E or Gelucire 44/14 in encouraging the GI absorption of drug was evident with the higher human effective permeability coefficient and fraction oral dose of drug absorbed from SSD in situ intestinal permeation study. In conclusion, in vivo studies in Wister rats demonstrated an improvement in the oral bioavailability of zaleplon from SSD over control pure drug suspension suggesting the competence of Gelucire 44/14 and TPGS E as conscientious carriers to augment the dissolution rate limited bioavailability of this active

Optimization of Nanostructured Lipid Carriers of Fenofibrate Using a Box-Behnken Design for Oral Bioavailability Enhancement

2021 ◽  
Vol 18 ◽  
Author(s):  
Huijuan Wang ◽  
Wei Hong ◽  
Xiangyu Li ◽  
Qian Jin ◽  
Weifeng Yea ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Nanostructured Lipid Carrier ◽  
Bioavailability Enhancement ◽  
Box Behnken Design ◽  
Predicted Values

Background: Fenofibrate (FNB) is a commonly used hypolipidemic agent. However, the oral bioavailability of FNB is limited by slow dissolution due to its low solubility. Thus, investigations on novel FNB formulations are necessary for their use. Objective: To enhance the oral bioavailability of FNB using optimized Nanostructured Lipid Carrier (NLC) formulations. Methods: Hot homogenization followed by ultrasonication was used to prepare FNB-NLCs. These formulations were optimized using a Box-Behnken design, where the amount of FNB (X1), a ratio of solid lipid/liquid lipid (X2), and the percentage of emulsifier (X3), were set as independent variables, while the particle size (Y1), and Entrapment Efficiency (EE%) (Y2), were used as dependent factors. An in vitro dissolution test was then performed using a paddle method, while an in vivo pharmacokinetic study of FNB-NLC formulation was performed in rats. Results: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. Results: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. Conclusion: A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

2019 ◽  
Vol 16 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Hadas Han ◽  
Sara Eyal ◽  
Emma Portnoy ◽  
Aniv Mann ◽  
Miriam Shmuel ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Nanoparticle Distribution ◽  
Spontaneous Seizures ◽  
Systemic Distribution ◽  
Hippocampal Ca1 ◽  
Pilocarpine Model

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

2001 ◽  
Vol 20 (10) ◽  
pp. 533-550 ◽  
Author(s):  
V Ciaravino ◽  
T McCullough ◽  
A D Dayan
Keyword(s):  
Ex Vivo ◽  
Reproductive Toxicity ◽  
In Vivo Studies ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Baxter Healthcare ◽  
Safety Margins ◽  
Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

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