scholarly journals A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

2021 ◽  
Vol 22 (22) ◽  
pp. 12406
Author(s):  
Emilia Jakubowska ◽  
Bartłomiej Milanowski ◽  
Janina Lulek
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Particle Morphology ◽  
Feed Concentration ◽  
Bottom Up ◽  
Antisolvent Precipitation ◽  
Process Characterization ◽  
Apparent Solubility ◽  
Poorly Soluble ◽  
Successful Approach

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form.

scholarly journals An impact of nanocrystals on dissolution rate of Lercanidipine: Supersaturation and crystallization by addition of solvent to antisolvent

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dolly Tulsibhai Gadhiya ◽  
Jayvadan K. Patel ◽  
Arti Arjanbhai Bagada
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Dissolution Rate ◽  
High Speed ◽  
Particle Morphology ◽  
In Vitro Dissolution ◽  
Antisolvent Precipitation ◽  
Pvp K30

Abstract Background Nanocrystals of any drug are pure solid drug particles with a mean diameter in nanometer range. Dissolution is a crucial factor for absorption of medicine in case of water-insoluble or poorly soluble drugs. The aim of this study was to develop nanocrystals of a hydrophobic drug, Lercanidipine, by addition of solvent to an antisolvent with high-speed homogenization to achieve dissolution and solubility enhancement. Addition of organic solvent to antisolvent results in genesis of nanosized particles due to fast nucleation process and rapid mixing. The nanosuspension was formulated using PVP K30 as a stabilizer. Further, nanosuspensions were lyophilized to convert into solid nanocrystals using mannitol as a cryoprotectant. The developed nanosuspensions were characterized for particle size, zeta potential, saturation solubility, and in vitro dissolution studies. Lyophilized solid nanocrystals were characterized for FTIR, SEM, XRD, and zeta potential (ζ). Results Central composite design was executed to study influence of amount of stabilizer and solvent to antisolvent ratio (independent variables) on particle size and % drug release at 10 min (dependent variables). The particle size of the developed Lercanidipine nanosuspensions were observed in the range of 302.00 ± 10.58 to 484.33 ± 6.51 nm measured by Zetatrac. A considerable increase was found in the solubility and dissolution rate of the nanocrystals as compared to pure drug. The drug release from Lercanidipine nanosuspensions was increased up to 88.95% within 10 min as compared to pure Lercanidipine which was only 21.53%. The X-ray diffraction study of lyophilized nanocrystals showed sharp and distinct peaks due to an increse in crystallinity of Lercanidipine Particle morphology was studied by scanning electron microscopy revealed that nanoprecipitated particles with lyophilization in the presence of mannitol exhibited dendrite needle-like crystals. Conclusion The nanocrystal development by antisolvent precipitation procedure using methanol as solvent, water as antisolvent, and low amounts of PVP K30 as stabilizer is a very promising and effective method to increase the dissolution rate of Lercanidipine. Graphical abstract

scholarly journals FABRICATION AND IN VITRO CHARACTERIZATION OF A NOVEL NANOSUSPENSION OF TELMISARTAN: A POORLY SOLUBLE DRUG PREPARED BY ANTISOLVENT PRECIPITATION TECHNIQUE USING 33 FACTORIAL DESIGN

2020 ◽  
pp. 286-294
Author(s):  
PRASANTA KUMAR MOHAPATRA ◽  
SIREESHA ◽  
VAIBHAV RATHORE ◽  
HARISH CHANDRA VERMA ◽  
BIBHUTI PRASAD RATH ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Dissolution Rate ◽  
Release Kinetics ◽  
Precipitation Method ◽  
Lauryl Sulfate ◽  
Poorly Soluble ◽  
Poorly Soluble Drug

Objective: The motivation behind the current examination was to build the solvency and dissolution rate of an antihypertensive drug telmisartan by the planning of nanosuspension by precipitation method at the research facility scale. We researched the nanoparticle manufacture of telmisartan employing a 33 factorial experimental configuration considering the impacts of nanosuspension on the physical, morphological, and dissolution properties of telmisartan. Methods: To get ready, nanosuspension particles of an ineffectively dissolvable drug are moreover of a drug solution to the anti-solvent leads to abrupt supersaturation and precipitation the making of nanoparticles. The nanosuspension particles of a poorly soluble drug loaded with urea and surfactants (sodium lauryl sulfate (SLS), poloxamer 188, Tween 80) have been prepared by a precipitation method. The nanosuspension particles were characterized for particle size, zeta potential, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), in vitro drug release, and release kinetics. Results: The readily optimized batch nanosuspension particles evaluated and exhibited the particle size (750 nm), zeta potential (-24.33 mV), differential scanning calorimetry (DSC) drug exhibited a change in crystalline form to amorphous, in vitro dissolution (F12 was higher 95% within 5 min) and drug release kinetics. The formulation parameter of surfactant concentration is optimized. Conclusion: The formulation of the nanosuspension approach has been shown to substantial improvement in the dissolution rate, thereby enhancing the oral bioavailability with the future development of this technology.

scholarly journals Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation

2021 ◽  
Vol 30 (1) ◽  
pp. 144-153
Author(s):  
Rusul M. Alwan ◽  
Nawal A. Rajab
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Precipitation Method ◽  
Antisolvent Precipitation ◽  
Prostacyclin Receptor ◽  
Pulmonary Arterial ◽  
Formulation Parameters ◽  
Long Acting

Selexipag is an orally selective long-acting prostacyclin receptor agonist, which indicated for the treatment of pulmonary arterial hypertension. It is practically insoluble in water ( class II, according to BCS). This work aims to prepare and optimized Selexipag nanosuspensions to achieve an enhancement in the in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of nanosuspension, and the effect of formulation parameters (stabilizer type, drug: stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size and polydispersity index were studied. SLPNS prepared with Soluplus® as amain stabilizer (F15) showed the smallest particle size 47nm with PDI and Zeta potential value of 0.073 and -47mV, respectively. SLPNS exhibited an increase in the dissolution rate in phosphate buffer pH 6.8 (100% drug release during 60 min) compared to the pure drug ( 40% during the same time). This result indicates that SLPNS is an efficient way of improving the dissolution rate.  

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.

scholarly journals FORMULATION AND EVALUATION OF POLYMERIC NANOSUSPENSION OF NARINGENIN

2017 ◽  
Vol 9 (6) ◽  
pp. 60 ◽  
Author(s):  
R. Sumathi ◽  
S. Tamizharasi ◽  
T. Sivakumar
Keyword(s):  
Particle Size ◽  
High Pressure ◽  
Dissolution Rate ◽  
Oral Bioavailability ◽  
Safety Evaluation ◽  
Drug Formulation ◽  
High Pressure Homogenization ◽  
Erythrocyte Hemolysis ◽  
Poorly Soluble

Objective: The objective of this study was to formulate and evaluate the poorly soluble drug, naringenin (NAR) into nanosuspension to increase the solubility and enhance the dissolution rate and then improve its bioavailability.Methods: Nanosuspenion of naringenin (NARNS) was prepared using high-pressure homogenization method using Soya lecithin, Polaxamer-407, Polaxamer-188, Hydroxypropyl methyl cellulose (HPMC) and Tween-80. Ten formulations were prepared to show the effect of stabilizer and its ratio. D-α-Tocopheryl polyethene glycol succinate 1000 (TPGS) was added as a co-stabilizer. All these formulations were evaluated for their particle size, PDI, zeta potential, FT-IR study, drug content, saturation solubility studies, entrapment efficiency, in vitro permeability and in vitro drug release. The formulation was further evaluated for scanning electron microscope (SEM), differential scanning calorimetry (DSC) and Powder X-ray diffraction (P-XRD) and hemocompatibility assessment.Results: All the prepared formulations were in the nano size. The optimum concentration of the stabilizer was in the formulation was found 1:1.5:1 (drug: stabilizer: co-stabilizer ratio). Dramatic effect of the particle size reduction was found by the addition of the co-stabilizer (TPGS) in formulation N2 that has P. S 80.52±0.13 nm. The solubility and dissolution of NAR in the form of NARNS were significantly higher than those of pure NAR. SEM report shows that naringenin nanosuspension revealed a smooth texture. P-XRD crystallography diffraction and DSC studies indicated that the crystalline state of NAR was converted into amorphous nature. The safety evaluation showed that NARNS provided a lower rate of erythrocyte hemolysis. Conclusion: In this study, (NARNS) was successfully carried out by high-pressure homogenization technique and characterized. The physio-chemical characterization shown that crystalline naringenin was converted to a polymorphic form (DSC and P-XRD Study) which evidenced by enhanced dissolution rate in comparisons of the formulation with (NAR) pure drug. The NARNS has shown 7.5±0.4 fold increased relative bioavailability when compared to the NAR. The increased drug dissolution rate may have a significant impact in absorption which in turn the improved oral bioavailability of naringenin. Thus, this delivery system may prefer to improve the dissolution of poorly soluble drugs like NAR and thus enhanced oral bioavailability. The safety evaluation showed that nanoformulation (NF2) shows a lower rate of erythrocyte hemolysis. These findings suggest that the selected formulation may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.

Development and Characterization of Oral Nanosuspension Using Esomeprazole Magnesium Trihydrate

2020 ◽  
Vol 10 (6) ◽  
pp. 909-917
Author(s):  
Surya Goel ◽  
Vijay Agarwal ◽  
Monika Sachdeva
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Dissolution Rate ◽  
Research Work ◽  
In Vitro Dissolution ◽  
Top Down ◽  
Bottom Up ◽  
Poloxamer 188 ◽  
Esomeprazole Magnesium

Background: Nanosuspension has arisen as a lucrative, remunerative, as well as a potent approach to improve the solubility and dissolution rate of poorly soluble drug entities. Several challenges are still present in this technology which need more research. Objective: The prime aim of this research work is to develop, optimize and characterize the oral nanosuspension using esomeprazole magnesium trihydrate as a drug candidate. Methods: The drug nanosuspensions were prepared using both approaches; Top-down and Bottom-up as the combinational approach. Poloxamer 188 was used as a stabilizer in this study. All the important formulation variables, like concentration of stabilizers that may influence characteristics of the nanosuspensions, were optimized. Formulation screening was performed using the optimization process, and the optimized nanosuspension was evaluated for its particle size, polydispersity index, zeta potential, shape, in vitro drug release and stability. Results: For optimization of drug nanosuspension, the effect of Poloxamer 188 concentration and esomeprazole concentration was investigated and the optimal values were 0.3% w/v and 4 mg/ml, respectively. The particle size of nanosuspensions was in the range of 185 to 1048 nm with varying the zeta potential values from -11.2 to -27.5 mV. The in vitro dissolution rate of esomeprazole was increased up to 3-folds, approximately (92% in 90 min) as compared with crude esomeprazole drug (31% in 90 min) due to the decrease in particle size. Conclusion: The result indicated that the combination of top-down and bottom-up approach used for preparing the oral nanosuspension is a suitable approach for poorly aqueous soluble drug moieties like esomeprazole magnesium.

Formulation and Evaluation of Nanosuspension Formulations of Ramipril using Hydrophilic Polymers

2015 ◽  
Vol 8 (1) ◽  
pp. 2735-2741
Author(s):  
Pankaj P Nerker ◽  
Hitendra Mahajan ◽  
Sagar Deore ◽  
Pradyumn Ige
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Hydrophilic Polymers ◽  
In Vitro Dissolution ◽  
Average Particle ◽  
Antisolvent Precipitation ◽  
Enhanced Dissolution

Nanosuspensions provide convenient formulations for improving the bioavailability and drug delivery. The objective of the investigation was to develop stable nanosuspension formulation of ramipril, with minimum surfactant concentration that could improve its solubility, stability and oral bioavailability. Ramipril is a potent antihypertensive drug, which act by inhibiting the angiotensin-converting enzyme. Nanosuspension was developed by antisolvent precipitation followed by high-pressure homogenization using hydrophilic polymers such as HPMC E5, HPMC E15, PVP K30, PVP K25, and PVA. The resulting nanosuspension was transformed into dry powder by freeze-drying process. Among all five formulations a formulation was choosen on the basis of results obtained from comparative study between different polymers based nanosuspension formulation of ramipril. The nanosuspension prepared was then evaluated for particle size, polydispesivity index, zeta potential, entrapment efficiency, saturated solubility study, scanning electron microscopy, differential scanning colorometry, and X ray diffraction. The combination of soya lecithin and pluronic F-68 as stabilizers yield nanosuspension with the smallest average particle size. The formulation of ramipril based on HPMC E 15 (Formulation B) shown enhanced dissolution rate. In which more than 60% of the drug was dissolved in the first 20 min compared to less than 25% of the pure drug within the same time period. The increase in the in vitro dissolution rate, nano size may favourably affect bioavailability.

Development, Characterization and Evaluation of Ritonavir Nanosuspension Treatment of Antiretroviral Therapy

2021 ◽  
pp. 297-304
Author(s):  
Shital V. Sonawane ◽  
Avish D. Maru ◽  
Mitesh P. Sonawane
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Poloxamer 407 ◽  
Precipitation Method ◽  
Average Particle ◽  
Solubility Study ◽  
Drug Content ◽  
Antisolvent Precipitation

Oral nanosuspension of ritonavir was prepared by antisolvent precipitation method using various polymers such as Eudragit RS100, Poloxamer 407, SLS and Methanol.The effect of eudragit RS100 and poloxamer 407 used stabilizer and SLS is surfactant was investigated on particle size and distribution, drug content, entrapment efficiency was observed. Ritonavir is having low solubility and low permeability drug belonging to class-IV according to BCS. Drug-excipient compatibility and amorphous nature of ritonavir drug is prepared nanosuspension was confirmed by FTIR, DSC and Motic microscope studies, respectively. The nanosuspension was further evaluated for drug content, saturation solubility study and entrapment efficiency. The average particle size of ritonavir nanaosuspensions formulas was observed from 0.006 µm to 0.017 µm. The studied in the solubility and dissolution rate there are the increase solubility and dissolution rate of ritonavir nanosuspension.

Dissolution Rate and Apparent Solubility of Poorly Soluble Drugs in Biorelevant Dissolution Media

2010 ◽  
Vol 7 (5) ◽  
pp. 1419-1430 ◽  
Author(s):  
Jonas H. Fagerberg ◽  
Oksana Tsinman ◽  
Na Sun ◽  
Konstantin Tsinman ◽  
Alex Avdeef ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Poorly Soluble Drugs ◽  
Biorelevant Dissolution ◽  
Apparent Solubility ◽  
Poorly Soluble ◽  
Biorelevant Dissolution Media

Solubility Enhancement of Poorly Soluble Drug Simvastatin by Solid Dispersion Technique

2016 ◽  
Vol 2 (2) ◽  
pp. 91-95
Author(s):  
Neelima Rani T ◽  
Pavani A ◽  
Sobhita Rani P ◽  
Srilakshmi N
Keyword(s):  
Dissolution Rate ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Onset Of Action ◽  
Kneading Method ◽  
Wetting Property ◽  
Poorly Soluble ◽  
Dispersion Technique ◽  
Low Solubility

This study aims to formulate solid dispersions (SDs) of Simvastatin (SIM) to improve the aqueous solubility, dissolution rate and to facilitate faster onset of action. Simvastatin is a BCS class II drug having low solubility & therefore low oral bioavailability. In the present study, SDs of simvastatin different drug-carrier ratios were prepared by kneading method. The results showed that simvastatin solubility & dissolution rate enhanced with polymer SSG in the ratio 1:7 due to increase in wetting property or possibly may be due to change in crystallinity of the drug.

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