scholarly journals In vitro and in vivo Evaluation of Ibuprofen Nanosuspensions for Enhanced Oral Bioavailability

2021 ◽  
Author(s):  
Mohsen Hedaya ◽  
Farzana Bandarkar ◽  
Aly Nada
Keyword(s):  
Particle Size ◽  
Tween 80 ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
In Vivo Evaluation ◽  
Poorly Soluble ◽  
Extent Of Absorption ◽  
Better Than

Introduction: The objectives were to prepare, characterize and in vivo evaluate different ibuprofen (IBU) nanosuspensions prepared by ultra-homogenization, after oral administration to rabbits. Methods: The nanosuspensions produced by ultra-homogenization were tested and compared with a marketed IBU suspension for particle size, in vitro dissolution and in vivo absorption. Five groups of rabbits received orally 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Serial blood samples were obtained after IBU administration. Results: The formulated nanosuspensions showed significant decrease in particle size. Polyvinyl Pyrrolidone K30 (PP) was found to improve IBU aqueous solubility much better than the other tested polymers. Addition of Tween 80 (TW), in equal amount as PP (IBU: PP:TW, 1:2:2 w/w) resulted in much smaller particle size and better dissolution rate. The Cmax achieved were 14.8±1.64, 11.1±1.37, 9.01±0.761, 7.03±1.38 and 3.23±1.03 μg/ml and the tmax were 36±8.2, 39±8.2, 100±17.3, 112±15 and 105±17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension were the highest for nanosuspension> unhomogenized suspension> nanoparticles> untreated IBU suspension. Conclusion: IBU/PP/TW nanosuspensions showed enhanced in vitro dissolution as well as faster rate and higher extent of absorption as indicated from the higher Cmax, shorter tmax and larger AUC. The in vivo data supported the in vitro results. Nanosuspensions prepared by ultra-high-pressure-homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.

DEVELOPMENT OF TOLCAPONE INCORPORATED SELF- MICRO EMULSIONS FOR SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (01) ◽  
pp. 32-37
Author(s):  
M Ganesh ◽  
◽  
B Chandra Shekar ◽  
Y. Madhusudan Rao
Keyword(s):  
Particle Size ◽  
Ternary Phase Diagram ◽  
In Vitro Dissolution ◽  
Size Analysis ◽  
Bioavailability Enhancement ◽  
Lipid Mixture ◽  
Poorly Soluble ◽  
Micro Emulsion

For BCS Class II and IV compounds, the main formulation objective is to increase the aqueous solubility of the API in the gastro - intestional fluids and maintain it in a solubilized state until it reaches the site of absorption. Lipid-based formulations including self-emulsifying formulations offer the potential for enhancing the absorption of poorly soluble and/or poorly permeable compounds. Self micro emulsion preparations are a obtained by a simple technique, with optimization of the composition based upon the ternary phase diagram. Tolcapone is an anti Parkinson agent, a poorly soluble drug, which is dissolved in the composition of oil and lipid mixture. Self micro emulsions are characterized by solubility study, particle size analysis, in vitro dissolution and in vivo bioavailability. The development of self micro emulsion formulations begins with the screening of excipients with the API in order to identify those that provides the best solubilization and chemical compatability. Particle size of the self micro emulsions below the 50 microns and the dispersive capacity of the multicomponent self micro emulsion gives homogenous emulsion in contact with aqueous media. In vitro drug release study showed that tolcapone self microemulsions increased in dissolution as compared to unformulated tolcapone drug and marketed product. In vivo increased absorption of the tolcapone micro emulsion formulation is 8.65 fold compared to the plain tolcapone and 1.07 fold compared to the marketed product.

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.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

scholarly journals Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

2007 ◽  
Vol 57 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Savita Vyas ◽  
Piyush Trivedi ◽  
Subhash Chaturvedi
Keyword(s):  
Human Plasma ◽  
Parent Drug ◽  
Aqueous Solubility ◽  
Spectrophotometric Analysis ◽  
In Vivo Evaluation ◽  
Gastrointestinal Side Effects ◽  
Molecular Masses ◽  
Anti Inflammatory

Ketorolac-dextran conjugates: Synthesis,in vitroandin vivoevaluationKetorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. Invitrohydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics.In vivobiological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

scholarly journals FORMULATION OF ATOVAQUONE TABLET USING BIOSURFACTANT IN A TERNARY SOLID DISPERSION SYSTEM: IN VITRO AND IN VIVO EVALUATION

2019 ◽  
pp. 44-49
Author(s):  
UDAYKUMAR B. BOLMAL ◽  
PRAMOD H. J.
Keyword(s):  
Ternary System ◽  
Solid Dispersion ◽  
Methyl Cellulose ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
In Vivo Evaluation ◽  
Enhanced Dissolution ◽  
Bioavailability Study

Objective: The goal of the present investigation was to improve the solubility and bioavailability of atovaquone tablet, using in-house biosynthesized biosurfactant in the ternary system of solid dispersion containing hydrophilic polymers with varying concentrations of biosurfactant. Atovaquone is an anti-malarial agent and belongs to biopharmaceutical classification system class IV. Methods: The solid dispersion of binary and ternary mixture was prepared using hydroxyl propyl methyl cellulose (HPMC) and biosurfactant respectively by a solvent evaporation method. All the atovaquone tablet formulations were prepared by incorporation of physical mixture, binary and ternary solid dispersed products with excipients by direct compression method. Pre-compression and post-compression parameters of atovaquone tablets were evaluated. In vivo bioavailability study was performed using female albino rabbits. Results: In vitro dissolution profile of binary and ternary system of solid dispersion products showed 8.65% and 34.64% respectively. Precompression and post-compression values of all atovaquone tablets formulations were within the specified limits. In vitro dissolution efficiency of F2 and F5 were 1.44 fold and 6.62 fold respectively, in accordance to the F1. In vivo study revealed that bioavailability of optimized formulation F5 was increased by 2.5 times and time to reach peak concentration was reduced to 1.4 h, in accordance to pure atovaquone suspension. Conclusion: Potential application of biosurfactant in the solid dosage form of atovaquone tablet was proved for enhanced dissolution rate and bioavailability of atovaquone for malaria treatment.

scholarly journals Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 328 ◽  
Author(s):  
Zhuang Ding ◽  
Lili Wang ◽  
Yangyang Xing ◽  
Yanna Zhao ◽  
Zhengping Wang ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Stability Study ◽  
Sprague Dawley ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0–∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

scholarly journals A Novel Sustained Anti-Inflammatory Effect of Atorvastatin—Calcium PLGA Nanoparticles: In Vitro Optimization and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1658
Author(s):  
Dalia H. Abdelkader ◽  
Ahmed Kh. Abosalha ◽  
Mohamed A. Khattab ◽  
Basmah N. Aldosari ◽  
Alanood S. Almurshedi
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
In Vitro Release ◽  
In Vivo Evaluation ◽  
Water Emulsion ◽  
Atorvastatin Calcium ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Atorvastatin Calcium (At-Ca) has pleiotropic effect as anti-inflammatory drug beside its main antihyperlipidemic action. Our study was conducted to modulate the anti-inflammatory effect of At-Ca to be efficiently sustained for longer time. Single oil-water emulsion solvent evaporation technique was used to fabricate At-Ca into polymeric nanoparticles (NPs). In vitro optimization survey was performed on Poly(lactide-co-glycolide) (PLGA) loaded with At-Ca regrading to particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (% EE), surface morphology and in vitro release pattern. In vitro drug-polymers interactions were fully scanned using Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning calorimetry (DSC) proving that the method of fabrication is an optimal strategy maintaining the drug structure with no interaction with polymeric matrix. The optimized formula with particle size (248.2 ± 15.13 nm), PDI (0.126 ± 0.048), zeta potential (−12.41 ± 4.80 mV), % EE (87.63 ± 3.21%), initial burst (39.78 ± 6.74%) and percent cumulative release (83.63 ± 3.71%) was orally administered in Male Sprague–Dawley rats to study the sustained anti-inflammatory effect of At-Ca PLGA NPs after carrageenan induced inflammation. In vivo results demonstrate that AT-Ca NPs has a sustained effect extending for approximately three days. Additionally, the histological examination revealed that the epidermal/dermal layers restore their typical normal cellular alignment with healthy architecture.

scholarly journals Formulation and Characterization of Felodipine as an Oral Nanoemulsions

2021 ◽  
Vol 30 (1) ◽  
pp. 209-217
Author(s):  
Sumaya B. Hamed ◽  
Shaimaa N. Abd Alhammid
Keyword(s):  
Particle Size ◽  
Oleic Acid ◽  
Zeta Potential ◽  
Water Solubility ◽  
Tween 80 ◽  
Aqueous Solubility ◽  
Compatibility Study ◽  
Drug Content ◽  
Drug Molecules

            Felodipine is a calcium-channel blocker with low aqueous solubility and bioavailability. Lipid dosage forms are attractive delivery systems for such hydrophobic drug molecules. Nanoemulsion (NE) is one of the popular methods that has been used to solve the dispersibility problems of many drugs. Felodipine was formulated as a NE utilizing oleic acid as an oil phase, tween 80 and tween 60 as surfactants and ethanol as a co-surfactant. Eight formulas were prepared, and different tests were performed to ensure the stability of the NEs, such as particle size, polydispersity index, zeta potential, dilution test, drug content, viscosity and in-vitro drug release. Results of characterization showed that felodipine nanoemulsion (F3) with (oleic acid 10%) ,(Smix 60% of tween80 :ethanol in a ratio of 3:1), (DDW 30%) was selected as the best formula, since it has a particle size of (17.01)nm, low PDI (0.392), zeta potential (-22.34mV), good dilution without drug precipitation , higher percent of drug content (99.098%) with  acceptable viscosity , and complete release of the drug after (45 min.) with significantly higher (P<0.05)   dissolution  rate in comparison with the pure drug powder. The selected formula (F3) subjected to further investigations as drug and excipient compatibility study by Fourier transform infrared spectroscopy (FTIR) The outcomes of the (FTIR) explain that the distinctive peaks for felodipine were not affected by other components and displayed the same functional group's band with very slight shifting. This indicates that there was no interaction between felodipine and other NE components. Therefore, these excipients were found to be compatible with felodipine. In conclusion, the NE was found to be an efficient method to enhance the dispersibility and permeatioins of drugs that have poor water solubility (lipophilic drugs).

scholarly journals Formulation and evaluation of self nano-emulsifying drug delivery system of ezetimibe for dissolution rate enhancement

2020 ◽  
Vol 11 (2) ◽  
pp. 1294-1301
Author(s):  
Geethanjali K ◽  
Vaiyana Rajesh C
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Dissolution Rate ◽  
Delivery System ◽  
Tween 80 ◽  
In Vitro Dissolution ◽  
Cinnamon Oil ◽  
Peg 400 ◽  
Solid Form

The present study was aimed to develop a Self Nano Emulsifying Delivery System of Ezetimibe (EZM) for enhancing its dissolution rate. Ezetimibe is a cholesterol absorption inhibitor, being a lipophilic drug due to its low solubility EZM shows a low dissolution profile. The SNEDDS formulation consisted of excipients Cinnamon oil, Tween 80, PEG 400 as the Oil, Surfactant and Co-surfactant. Twelve formulations with different ratios of Oil, Surfactant and Co-surfactant were prepared. The liquid SNEDDS were then converted into Solid form by adsorption technique using Avicel PH 101 and Aerosil 200 as adsorbents. The liquid SNEDDS was characterised for Particle size, Emulsification time, Dispersibility, percentage transmittance, PCM, Centrifugation, Cloud Point and Freeze thaw cycle. The solid form was characterized for the flow property, SEM, Drug content and in-vitro dissolution. Among the twelve formulations F6 formulation was found to have a particle size of 196 nm and PDI of 0.123. F6 formulation was selected as the best and it was made into solid by adsorption onto solid carriers. The F6 formulation consisted of the 25% Cinnamon oil, 50% tween 80 and 25% PEG 400. The in-vitro dissolution rate of the prepared formulation was compared with the marketed formulation. The in-vitro dissolution data showed that the drug release at the end of 60 mins from marketed formulation was 63.75 % and from SNEDDS formulation was         90.62 %. The dissolution rate of the prepared SNEDDS was increased by 1.42 times than the marketed formulation. The increase in the dissolution rate shows that SNEDDS is a suitable drug delivery system to enhance the rate of dissolution of Ezetimibe.

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