scholarly journals Mechanism of Dissolution Enhancement and Bioavailability of Poorly Water Soluble Celecoxib by Preparing Stable Amorphous Nanoparticles

2010 ◽  
Vol 13 (4) ◽  
pp. 589 ◽  
Author(s):  
Yinghui Liu ◽  
Changshan Sun ◽  
Yanru Hao ◽  
Tongying Jiang ◽  
Li Zheng ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Water Soluble ◽  
Promising Method ◽  
Photoelectron Spectra ◽  
Drug Dissolution ◽  
X Ray ◽  
Antisolvent Precipitation ◽  
Ft Ir ◽  
Poorly Water Soluble

Purpose: Nanoparticle engineering offers promising methods for the formulation of poorly water soluble drug compounds. The aim of the present work was to enhance dissolution and oral bioavailability of poorly water-soluble celecoxib (CXB) by preparing stable CXB nanoparticles using a promising method, meanwhile, investigate the mechanism of increasing dissolution of CXB. Methods: CXB nanoparticles were produced by combining the antisolvent precipitation and high pressure homogenization (HPH) approaches in the presence of HPMC E5 and SDS (2:1, w/w). Then the CXB nanosuspensions were converted into dry powders by spray-drying. The effect of process variables on particle size and physical state of CXB were investigated. The physicochemical properties of raw CXB and CXB nanoparticles were characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), X-ray photoelectron spectra (XPS), fourier transform infrared (FT-IR) spectroscopy, diffrential scanning calorimetry (DSC), as well as, measuring the particle size and contact angle. Additionally, the studies of in-vitro drug dissolution and oral bioavailability in beagle dogs of nanoparticles were performed. Results: The images of SEM revealed spherical CXB nanoparticles. The DSC and XRPD results indicated that the antisolvent precipitation process led to the amorphization of CXB. Under storage, the amorphous CXB nanoparticles showed promising physical stability. The XPS data indicated the amorphous CXB nanoparticles exhibited different surface property compared to raw CXB. Hydrogen bonds were formed between the raw CXB and HPMC E5 as proven by the FT-IR spectra. CXB nanoparticles increased the saturation solubility of CXB fourfold. CXB nanoparticles completely dissolved in the dissolution medium of phosphate buffer (pH 6.8, 0.5% SDS) within 5 min, while there was only 30% of raw CXB dissolved. The Cmax and AUC0–24h of CXB nanoparticles were approximately threefold and twofold greater than those of the Celecoxib Capsules, respectively. Conclusions: The process by combining the antisolvent precipitation under sonication and HPH was a promising method to produce small, uniform and stable CXB nanoparticles with markedly enhanced dissolution rate and oral bioavailability due to an increased solubility that is attributed to a combination of amorphization and nanonization with increased surface area, improved wettability and reduced diffusion pathway.

In Vitro and In Vivo Evaluation of Olmesartan Medoxomil Microcrystals and Nanocrystals: Preparation, Characterization, and Pharmacokinetic Comparison in Beagle Dogs

2019 ◽  
Vol 16 (6) ◽  
pp. 500-510
Author(s):  
Rong Chai ◽  
Hailing Gao ◽  
Zhihui Ma ◽  
Meng Guo ◽  
Qiang Fu ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Olmesartan Medoxomil ◽  
Water Soluble ◽  
Size Reduction ◽  
Drug Dissolution ◽  
Beagle Dogs ◽  
Enhanced Solubility

Background: Olmesartan medoxomil (OLM) is a promising prodrug hydrolyzed to olmesartan (OL) during absorption from the gastrointestinal tract. OL is a selective angiotensin II receptor antagonist, with high drug resistance and low drug interaction. However, OLM has low solubility and low bioavailability. Therefore, it is extremely urgent to reduce the drug particle size to improve its biological bioavailability. Objective: The aim of the study was to improve the oral bioavailability of poorly water-soluble olmesartan medoxomil (OLM) by using different particle size-reduction strategies. Method: Raw drug material was micronized or nanosized by either jet or wet milling processes, respectively. The particle sizes of the prepared nanocrystals (100-300 nm) and microcrystals (0.5-16 μm) were characterized by DLS, SEM, and TEM techniques. Solid state characterization by XPRD and DSC was used to confirm the crystalline state of OLM after the milling processes. Results: We demonstrated that OLM nanocrystals enhanced solubility and dissolution in the non-sink condition in which high sensitivity was found in purified water. After 1 h, 65.4% of OLM was dissolved from nanocrystals, while microcrystals and OLMETEC® only showed 37.8% and 31.9% of drug dissolution, respectively. In the pharmacokinetic study using Beagle dogs, an increase in Cmax (～2 fold) and AUC (～1.6 fold) was observed after oral administration of OLM nanocrystals when compared to microcrystals and reference tablets, OLMETEC®. In contrast, OLM microcrystals failed to improve the oral bioavailability of the drugs. Conclusion: Particles size reduction to nano-scale by means of nanocrystals technology significantly increased in vitro dissolution rate and in vivo oral bioavailability of OLM.

scholarly journals NOVEL APPLICATION OF MIXED HYDROTROPIC SOLUBILIZATION TECHNIQUE IN THE FORMULATION AND EVALUATION OF SOLID DISPERSION OF FLUPIRTINE MALEATE

2018 ◽  
Vol 8 (5) ◽  
pp. 481-488
Author(s):  
Nisha Kumari Yadav ◽  
Tripti Shukla ◽  
Neeraj Upmanyu ◽  
Sharad Prakash Pandey ◽  
Mohammad Azaz Khan
Keyword(s):  
Particle Size ◽  
Solid Dispersion ◽  
Sodium Benzoate ◽  
Oral Bioavailability ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Evaporation Technique ◽  
Poorly Water Soluble

Flupirtine is an amino pyridine derivative that functions as a centrally acting non-opioid, non-steroidal analgesic. It is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties. Its muscle relaxant properties make it popular for back pain and other orthopedics uses. In the present investigation, recently developed mixed hydrotropic solid dispersion technology precludes the use of organic solvent and also decreases the individual concentration of hydrotropic agents, simultaneously decreasing their toxic potential. Mixed-hydrotropic solubilisation technique is the experience to increase the solubility of poorly water soluble drugs in the aqueous solution containing blends of hydrotropic agents, which may give synergistic enhancement effect on solubility of poorly water-soluble drugs and to reduce concentrations of each individual hydrotropic agent to minimize their toxic effects due to high concentration of hydrotropic agents. The Flupirtine loaded solid dispersion was prepared by a solvent evaporation technique using sodium benzoate and a niacinamide hydrotropic mixture. The prepared solid dispersions were valuated regarding their solubility, mean particle size, in-vitro drug release. The prepared solid dispersions were found very stable (chemically). The superior dissolution rate due to its reduced particle size may have contributed to the increased oral bioavailability. This study demonstrated that mixed-solvency may be an alternative approach for poorly soluble drugs to improve their solubility and oral bioavailability. Keywords: Flupirtine, Solid dispersion, Mixed-hydrotropic solubilisation, Solvent evaporation technique, Sodium benzoate, Niacinamide

scholarly journals Formulation and In Vitro Evaluation of Casein Nanoparticles as Carrier for Celecoxib

2020 ◽  
Vol 10 (3) ◽  
pp. 408-417
Author(s):  
Jyotsana R. Madan ◽  
Izharahemad N. Ansari ◽  
Kamal Dua ◽  
Rajendra Awasthi
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Water Soluble ◽  
Polydispersity Index ◽  
Drug Dissolution ◽  
Permeation Studies ◽  
Poorly Water Soluble

Purpose : The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). Methods: The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further, in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. Results: The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. The in vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time point than that of the pure CLXB. Conclusion: The study explored the potential of CAS as a carrier for solubility enhancement of poorly water soluble drugs.

DISSOLUTION ENHANECEMENT OF AN ANTIHYPERTENSIVE AGENT BY SOLID DISPERSION

2013 ◽  
pp. 21-24
Author(s):  
Keyword(s):  
Solid Dispersion ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
X Ray Diffraction ◽  
Peg 6000 ◽  
X Ray ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Purposes: To evaluate dissolution enhancement of IS, a poorly water-soluble drug, by PEG 6000-based solid dispersion and investigate mechanism of dissolution enhancement from the solid dispersion. Methods: Solid dispersion was prepared by melting method. Dissolution test was performed at pH 6.8. Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) were used to investigate the drug crystallinity as well as the interaction between drug and polymer. Results: Dissolution rate of IS from the solid dispersion was significantly increased at pH 6.8 as compared to the pure drug. Drug crystallinity was reduced. FTIR showed the interaction between polymer and IS in the solid dispersion. Conclusions: PEG 6000 was successfully used to increase the dissolution of IS. Moreover, mechanism of the dissolution enhancement was fully explained in the study. Key words: poorly water-soluble drug, dissolution, solid dispersion.

Behaviour of Lipid-Based Formulations Containing Nifedipine in Aqueous Media as Observed by Small Angle X-Ray Scattering

2013 ◽  
Vol 747 ◽  
pp. 139-142 ◽  
Author(s):  
Yotsanan Weerapol ◽  
Mont Kumpugdee-Vollrath ◽  
Pornsak Sriamornsak
Keyword(s):  
Small Angle ◽  
Castor Oil ◽  
Aqueous Media ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
X Ray ◽  
X Ray Scattering ◽  
Poorly Water Soluble ◽  
Ray Scattering

Lipid-based formulations (LBF) including self-emulsifying drug delivery system have been used to improve drug dissolution and bioavailability by avoiding rate-limiting step during dissolution of poorly water-soluble drugs. This study was aimed to investigate the behavior of lipid-based formulations upon dilution in aqueous media by using small angle X-ray scattering (SAXS). LBF is composed of oil (caprylic/capric glyceride), surfactants (polyoxyl 35 castor oil or polyoxyl 40 hydrogenated castor oil), and co-solvent (diethylene glycol monoethyl ether) at a weight ratio of 1:1:8. Nifedipine, a poorly water-soluble drug, was used as a model drug. A 100-fold dilution of the LBF in aqueous media (i.e., simulated gastric fluid USP without pepsin (SGF) and distilled water) resulted in nanosized emulsion (less than 200 nm). The selected formulations were diluted in aqueous media at various ratios (e.g., 0.01, 0.02, 0.04, 0.06, 0.09, 0.11, 0.18, 0.25, 0.67, 1.5, 4, 99, 199 and 300 folds) and then, after equilibrium, monitored by SAXS in order to observe the surfactant rearrangement. The results from SAXS scattering curves (qof 0.027-0.980 Å-1) demonstrated that a lamellar phase or liquid crystalline was not formed upon dilution. The emulsions were formed without the ordered structure.

NANO-SIZED SOLID DISPERSION OF A POORLY WATER-SOLUBLE DRUG

2012 ◽  
pp. 31-35
Author(s):  
Truong Dinh Thao Tran ◽  
Ha Lien Phuong Tran ◽  
Nghia Khanh Tran ◽  
Van Toi Vo
Keyword(s):  
Drug Release ◽  
Droplet Size ◽  
Solid Dispersion ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
Particle Size Reduction ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Purposes: Aims of this study are dissolution enhancement of a poorly water-soluble drug by nano-sized solid dispersion and investigation of machenism of drug release from the solid dispersion. A drug for osteoporosis treatment was used as the model drug in the study. Methods: melting method was used to prepare the solid dispersion. Drug dissolution rate was investigated at pH 1.2 and pH 6.8. Drug crystallinity was studied using differential scanning calorimetric and powder X-ray diffraction. In addition, droplet size and contact angle of drug were determined to elucidate mechanism of drug release. Results: Drug dissolution from the solid dispersion was significantly increased at pH 1.2 and pH 6.8 as compared to pure drug. Drug crystallinity was changed to partially amorphous. Also dissolution enhancement of drug was due to the improved wettability. The droplet size of drug was in the scale of nano-size when solid dispersion was dispersed in dissolution media. Conclusions: nano-sized solid dispersion in this research was a successful preparation to enhance bioavailability of a poorly water-soluble drug by mechanisms of crystal changes, particle size reduction and increase of wet property.

scholarly journals Modification of Wood with Monoethanolamino-borate by The Data of X-Ray Photoelectron Spectroscopy

2018 ◽  
Vol 196 ◽  
pp. 04005
Author(s):  
Irina Stepina ◽  
Irina Kotlyarova
Keyword(s):  
Particle Size ◽  
Photoelectron Spectroscopy ◽  
Model Compound ◽  
Hydrolytic Stability ◽  
Photoelectron Spectra ◽  
Wood Cellulose ◽  
Rapid Loss ◽  
X Ray ◽  
Wood Protection ◽  
Cellulose Materials

The difficulty of wood protection from biocorrosion and fire is due to the fact that modifiers in use are washed out from the surface of the substrate under the influence of environmental factors. This results in a rapid loss of the protective effect and other practically important wood characteristics caused by the modification. To solve this problem is the aim of our work. Here, monoethanolaminoborate is used as a modifier, where electron-donating nitrogen atom provides a coordination number equal to four to a boron atom, which determines the hydrolytic stability of the compounds formed. Alpha-cellulose ground mechanically to a particle size of 1 mm at most was used as a model compound for the modification. X-ray photoelectron spectra were recorded on the XSAM-800 spectrometer (Kratos, UK). Prolonged extraction of the modified samples preceded the registration of the photoelectron spectra to exclude the fixation of the modifier molecules unreacted with cellulose. As a result of the experiment, boron and nitrogen atoms were found in the modified substrate, which indicated the hydrolytic stability of the bonds formed between the modifier molecules and the substrate. Therefore monoethanolaminoborate can be considered as a non-extractable modifier for wood-cellulose materials.

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