Design, Fabrication and Characterization of Esomeprazole Nanocrystals for Enhancing the Dissolution Rate and Stability

2020 ◽  
Vol 14 ◽  
Author(s):  
Vijay Agarwal ◽  
Meenakshi Bajpai
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Crystalline State ◽  
Physical Mixture ◽  
Water Soluble ◽  
Dissolution Behavior ◽  
Physical Treatment ◽  
Pxrd Pattern ◽  
Freeze Dried ◽  
Bulk Drug

Background: Poor solubility and low dissolution rate limit the work at poorly water-soluble drugs like Esomeprazole. To overcome this problem, different technologies had to be used but could not resolve the problem, significantly. The main aim of this study was to prepare the nanocrystals using evaporative precipitation ultrasonication method in order to improve the dissolution rate and stability of Esomeprazole (ESM). Methods: For getting the nanocrystals, different nanoformulations were prepared using the pluronic F-68 in different concentration, and then screened formulation was lyophilized in presence of two distinct cryoprotectants; mannitol and sucrose. The obtained nanocrystals were characterized for their re-dispersibility, crystalline state, dissolution behavior, particle size, polydispersibility index and morphology. Dissolution study of ESM nanocrystals was performed in buffer solution of pH-7.4, and compare to that of bulk ESM sample and ESM/pluronic F-68 physical mixture. Results: Cryoprotectant containing nanocrystals exhibit the re-dispersion in water after the manual shaking. 5% mannitol containing nanocrystals showed the least polydispersity index (0.42 ± 0.11) and narrowest particle size (186 ± 12.9 nm). The powder x-ray diffraction (PXRD) pattern and differential scanning calorimeter (DSC) thermograms revealed that crystalline state of drug was not changed after the different physical treatment. Freeze-dried nanocrystals showed a faster dissolution rate and almost 99.45% of drug was released within 60 min. However, the bulk drug and a physical mixture of bulk drug/pluronic F-68 showed only 22.65% and 21.3% of drug release, respectively, after 60 min. Conclusion: The different findings revealed that nanocrystals could be a potential alternate for solving the dissolution rate and stability issue of ESM like poorly soluble drugs.

Solubility Enhancement of the Poorly Water-Soluble Antiulcer Drug Famotidine by Inclusion Complexation

2013 ◽  
Vol 6 (1) ◽  
pp. 1983-1989 ◽  
Author(s):  
Shabnam Ain ◽  
V Gupta ◽  
Babita K ◽  
Q Ain ◽  
J Dahiya
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Phosphate Buffer ◽  
Physical Mixture ◽  
Water Soluble ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Distilled Water ◽  
Physicochemical Interaction ◽  
Mixture Phase

Aqueous solubility is a critical factor for optimum drug delivery. In the present study, we investigated the potential of drug-cyclodextrin complexation as an approach for improving the solubility and bioavailability of famotidine, an H2-receptor antagonist and acid reducing drug which has poor solubility and bioavailability. Solubility improvement of drug by β-cyclodextrin was done by simple complexation approach using physical, kneading and co-precipitation methods and compared with physical mixture. Phase solubility profile indicated that the solubility of famotidine was significantly increased in presence of β-cyclodextrin and shows a linear graph with β-cyclodextrin indicating formation of inclusion complexes in a 1:1 molar ratio. β-Cyclodextrin-famotidine mixture have maximum stability constant 1477.6 M-1. The inclusion complex ratio 1:1 of kneading mixture was selected based on drug release profile and compared with physical mixture. Further characterization was done by  using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) to identify the physicochemical interaction between drug and carrier and its effect on dissolution. Dissolution rate studies for selected inclusion complex was performed in 0.1 N HCl (pH 1.2), phosphate buffer (pH 7.5) and distilled water (pH 6.8) and compared these to pure drug profile which was found to be 2.34 fold increase in distilled water, 1.83 fold in HCl and 2.01 fold in phosphate buffer (pH 7.5). These results suggest that the kneaded complex of famotidine with β-cyclodextrin as hydrophilic complexation agent can substantially enhance the solubility and dissolution rate. Such complex has promising potential to improve the bioavailability of famotidine.  

scholarly journals Enhancement of Solubility and Improvement of Dissolution Rate of Atorvastatin Calcium Prepared as Nanosuspension

2019 ◽  
Vol 28 (2) ◽  
pp. 46-57
Author(s):  
Ahmed H. Ali ◽  
Shaimaa N. Abd-Alhammid
Keyword(s):  
Particle Size ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Precipitation Method ◽  
Size Analysis ◽  
Dissolution Profile ◽  
Disintegration Time ◽  
Atorvastatin Calcium ◽  
Freeze Dried

       Atorvastatin have problem of very slightly aqueous solubility (0.1-1 mg/ml). Nano-suspension is used to enhance it’s of solubility and dissolution profile. The aim of this study is to formulate Atorvastatin as a nano-suspension to enhance its solubility due to increased surface area of exposed for dissolution medium, according to Noyes-Whitney equation.         Thirty one formulae were prepared to evaluate the effect of ; Type of polymer, polymer: drug ratio, speed of homogenization, temperature of preparation and inclusion of co-stabilizer in addition to the primary one; using solvent-anti-solvent precipitation method under high power of ultra-sonication. In this study five types of stabilizers (TPGS, PVP K30, HPMC E5, HPMC E15, and Tween80) were used in three different concentrations 1:1, 1:0.75 and 1:0.5 for preparing of formulations. At the same time, tween80 and sodium lauryl sulphate have been added as a co-stabilizer.          Atorvastatin nano-suspensions were evaluated for particle size, PDI, zeta potential, crystal form and surface morphology. Finally, results of particle size analysis revealed reduced nano-particulate size to 81nm for optimized formula F18 with the enhancement of in-vitro dissolution profile up to 90% compared to 44% percentage cumulative release for the reference Atorvastatin calcium powder in 6.8 phosphate buffer media. Furthermore, saturation solubility of freeze dried Nano suspension showed 3.3, 3.8, and 3.7 folds increments in distilled water, 0.1N Hcl and 6.8 phosphate buffers, respectively. Later, freeze dried powder formulated as hard gelatin capsules and evaluated according to the USP specifications of the drug content and the disintegration time.        As a conclusion; formulation of poorly water soluble Atorvastatin calcium as nano suspension significantly improved the dissolution of the drug and enhances its solubility.

scholarly journals Dissolution rate and bioavailability enhancement of co-ground mixtures of paliperidone, with different hydrophilic carriers

2013 ◽  
Vol 2 (3) ◽  
pp. 70-77 ◽  
Author(s):  
Anuja Pandey ◽  
Bhabagrahi Rath ◽  
Anil Kumar Dwivedi
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Methyl Cellulose ◽  
Pharmaceutical Journal ◽  
Water Soluble ◽  
Vinyl Pyrrolidone ◽  
Particle Size Reduction ◽  
Bioavailability Enhancement ◽  
Ground Mixture ◽  
Crystalline Nature

Co-ground mixtures of poorly water soluble drug Paliperidone (PAL) with different hydrophilic carriers [Polyvinylpyrrolidine (Plasdone K-25 and Plasdone S-630), Hydroxypropyl methyl cellulose (HPMC), Hydroxypropylcellulose (HPC) and Sodium alginate were prepared to improve the dissolution rate of PAL. Co-grinding with PVP, especially with PVP- S630 (Vinyl pyrrolidone/ vinyl acetate co-polymer), was more effective in reduction of particle size than milling of drug alone. DSC studies indicated that crystalline nature of drug was reduced after co-grinding with PVP grades as compared to their corresponding physical mixtures. The hydrophilic carriers other than PVP did not reduce the crystalline nature of the drug significantly. X-ray diffraction (XRD) was carried out for selected batches to confirm DSC results. Significant enhancement in dissolution rate as well as extent was observed with co-ground mixtures of drug and PVP. Among all the prepared batches in this study, co-ground mixture of PAL and Plasdone S-630 in 1:1 ratio showed best results in terms of extent of dissolution as well as dissolution rate in water. This effect was not only due to particle size reduction, but also loss of crystalline nature of the drug during co-grinding. PVP was found to be a better carrier among the different hydrophilic carriers used in the study for improving the dissolution characteristics of PAL. The extent of the mean plasma exposures of PAL was 7-fold higher in animals treated with co-ground mixture of PAL, Plasdone S630 (1:1) compared to animals treated with Pure PAL.DOI: http://dx.doi.org/10.3329/icpj.v2i3.13632 International Current Pharmaceutical Journal, February 2013, 2(3): 70-77 

scholarly journals Dissolution rate enhancement of gliclazide by ordered mixing

2011 ◽  
Vol 61 (3) ◽  
pp. 323-334 ◽  
Author(s):  
Vikas Saharan ◽  
Pratim Choudhury
Keyword(s):  
Particle Size ◽  
Sodium Chloride ◽  
Dissolution Rate ◽  
Drug Concentration ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Cube Root ◽  
Particle Size Range ◽  
Rate Enhancement ◽  
Dissolution Rate Enhancement

Dissolution rate enhancement of gliclazide by ordered mixingThe poorly water soluble antidiabetic drug gliclazide was selected to study the effect of excipients on dissolution rate enhancement. Ordered mixtures of micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium chloride were prepared by manual shaking of glass vials containing the drug and excipient(s). Different water soluble excipients, addition of surfactant and superdisintegrant, drug concentration and carrier particle size influenced the dissolution rate of the drug. Dissolution rate studies of the prepared ordered mixtures revealed an increase in drug dissolution with all water soluble excipients. The order of dissolution rate improvement for gliclazide was mannitol > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the particle size range 355-710 μm were superior in increasing the drug dissolution rate from ordered mixtures. Reducing the carrier particle size decreased the dissolution rate of the drug as well as the increase in drug concentration. Kinetic modeling of drug release data fitted best the Hixson-Crowell model, which indicates that all the ordered mixture formulations followed the cube root law fairly well.

scholarly journals Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2061
Author(s):  
Jeong-Soo Kim ◽  
Heejun Park ◽  
Eun-Sol Ha ◽  
Kyu-Tae Kang ◽  
Min-Soo Kim ◽  
...  
Keyword(s):  
Particle Size ◽  
Surface Layer ◽  
Dissolution Rate ◽  
Spray Drying ◽  
Supercritical Fluid ◽  
Water Soluble ◽  
Size Reduction ◽  
Particle Size Reduction ◽  
Surface Active ◽  
Poorly Water Soluble

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 μm) compared to that of unprocessed fenofibrate (approximately 20 μm) and SD-processed particles (approximately 40 μm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

scholarly journals Effect of Carrier Lipophilicity and Preparation Method on the Properties of Andrographolide–Solid Dispersion

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 74 ◽  
Author(s):  
Guowei Zhao ◽  
Qingyun Zeng ◽  
Shoude Zhang ◽  
Youquan Zhong ◽  
Changhao Wang ◽  
...  
Keyword(s):  
Surface Morphology ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Preparation Method ◽  
Water Soluble ◽  
Vacuum Drying ◽  
Dissolution Behavior ◽  
Drying Method ◽  
Carrier Material ◽  
Poorly Water Soluble

Solid dispersion (SD) is a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble drugs. This work investigated the effects of carrier material lipophilicity and preparation method on the properties of andrographolide (AG)–SD. The SDs of AG and the carrier materials, polyethylene glycol (PEG) and PEG grafted with carbon chains of different length (grafted PEG), have been prepared by spray-drying and vacuum-drying methods. In AG–SDs prepared by the different preparation methods with the same polymer as carrier material, the intermolecular interaction, 5% weight-loss temperature, the melting temperature (Tm), surface morphology, crystallinity, and dissolution behavior have significant differences. In the AG–SDs prepared by the same spray-drying method with different grafted PEG as carrier material, Tm, surface morphology, crystallinity, and dissolution behavior had little difference. In the AG–SDs prepared by the same vacuum-drying method with different grafted PEG as carrier material, the crystallinity and Tm decreased, and the dissolution rate of AG increased with the increase of grafted PEG lipophilicity. The preparation method has an important effect on the properties of SD. The increase of carrier material lipophilicity is beneficial to the thermal stability of SD, the decrease of crystallinity and the increase of dissolution rate of a poorly water-soluble drug in the SD.

Design, Optimization and in vitro Characterization of Dasatinib loaded PLGA Nano carrier for Targeted cancer therapy: A Preliminary Evaluation

2021 ◽  
pp. 2095-2100
Author(s):  
Shyam S Kumar ◽  
G. Gopalakrishnan ◽  
N. L. Gowrishankar
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Surface Morphology ◽  
Dissolution Rate ◽  
Water Soluble ◽  
Spherical Particles ◽  
Preliminary Evaluation ◽  
Pluronic F68

Objective: Drug nanoparticles offer a versatile platform for enhancing the dissolution rate and bioavailability of poorly water soluble drugs The present study was aimed to design and develop dasatinib (DAS) loaded Poly lactide co glycolic acid (PLGA) to enhance the dissolution rate and to study the effect of formulation variables for the BCS class II drug dasatinib for the treatment of chronic myeloid leukemia. Methods: The DAS loaded Nps were prepared by using modified double emulsion solvent evaporation method (DESE) using different stabilizers, the formulated Nps were characterized for particle size, zeta potential, Poly Dispersity Index, Surface morphology, Drug entrapment and Invitro drug release. Results: The DAS loaded NP s showed the lowest particles size of 123 nm and zeta potential of – results of Pluronic F68 loaded NP showed the lowest particle size of – and highest zeta potential of --. Surface morphology of NPs with DMAB showed distinct smooth spherical particles with the size range of 50nm. Morphology of Pluronic F68 formulated NPs showed the high degree of aggregation. In vitro drug release showed up to 24hrs in a sustained manner. Conclusion: The result of our study indicates the use of PLGA as a sustained release polymer and using DMAB as a stabilizer for better stable formulation.

scholarly journals Preparation and Characterization of Nimesulide Nanoparticles For Dissolution Improvement

2018 ◽  
pp. 46-60
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Precipitation Method ◽  
Scanning Calorimetry ◽  
Decrease Particle Size ◽  
Antisolvent Precipitation ◽  
Particle Size Analyzer ◽  
Particle Size Increase ◽  
Freeze Dried ◽  
Inflammatory Drugs

Nimesulide is one of the types of non-steroidal anti-inflammatory drugs, widely used as analgesic and antipyretic. It is classified as class II drugs according to BCS guidance because of low solubility in water that leads to decrease in dissolution rate. So, the objective of this study was to decrease particle size, increase solubility and dissolution rate of nimesulide by preparation of nimesulide nanoparticles using solvent/antisolvent precipitation method by addition of organic solution of drug onto the solution of stabilizer. The size of nimesulide nanoparticles were studied and considered by particle size analyzer, drug content and loading efficiency. The freeze-dried nanoparticles were characterized by field emission electron microscope, X-Ray powder diffraction, differential scanning calorimetry and saturated solubility measurement. Tablet was manufactured by direct compression. The tablets were evaluated for drug release to measure the effect of nanoparticles on the dissolution improvement of drug.

Dissolution behavior of Olmesartan Medoxomil drug in Polymeric Micelles of Soluplus and Pluronic F127

2021 ◽  
pp. 2200-2204
Author(s):  
Suchetana Dutta ◽  
P. K. Kulkarni ◽  
Shailesh T.
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Olmesartan Medoxomil ◽  
Water Soluble ◽  
Pluronic F127 ◽  
Dissolution Behavior ◽  
Compatibility Study ◽  
Poorly Water Soluble

The aim of the present work was to study the dissolution behaviour of a poorly water-soluble Olmesartan Medoxomil (class II drug), by forming polymeric micelles (PMs) of SoluPlus and Pluronic F127. Polymeric Micelles of SoluPlus and Pluronic F127 were prepared by the co-solvent evaporation method. Drug and excipient compatibility study were carried out by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry. The formulations were evaluated for particle size, Zeta Potential, Solubility studies, drug loading and encapsulation efficiency. Scanning Electron Microscopy (SEM) analysis was performed to study the surface morphology of the PMs. The SEM images showed spherical surface of the micelles. The drug loading efficiency was more for SoluPlus micelles compared to Pluronic F127 micelles. The Polymeric micelles showed negative zeta potential value indicating that they are stable and resist aggregation. The particle size was around 100nm and polydispersity index was less than 1 indicating uniform size distribution. The drug release from the SoluPlus micelles was higher than the Pluronic micelles. These results suggest that the polymeric micelles can be used to increase the solubility of poorly water-soluble drugs.

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