scholarly journals Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 605 ◽  
Author(s):  
Mary-Carmel Kearney ◽  
Peter E. McKenna ◽  
Helen L. Quinn ◽  
Aaron J. Courtenay ◽  
Eneko Larrañeta ◽  
...  
Keyword(s):  
Nile Red ◽  
Aqueous Solubility ◽  
Log P ◽  
Reservoir Properties ◽  
Peg 400 ◽  
Drug Molecules ◽  
Hydrophobic Compounds ◽  
Custom Made ◽  
Poorly Soluble ◽  
Poly Ethylene

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.

scholarly journals Solubility Enhancement of Cox-II Inhibitors by Cosolvency Approach

1970 ◽  
Vol 7 (2) ◽  
pp. 119-126 ◽  
Author(s):  
PR Sathesh Babu ◽  
CVS Subrahmanyam ◽  
J Thimmasetty ◽  
R Manavalan ◽  
K Valliappan ◽  
...  
Keyword(s):  
Interaction Mechanism ◽  
Chemical Properties ◽  
Aqueous Solubility ◽  
Dosage Forms ◽  
Solubility Enhancement ◽  
Peg 400 ◽  
Drug Molecules ◽  
Poorly Soluble ◽  
Solvent Blends ◽  
Major Factors

Solubility enhancement of meloxicam and rofecoxib, which are poorly soluble in water, was attempted. These are available in the form of solid dosage forms but not in solution dosage forms due to their low aqueous solubility. In this work, aqueous solubility of meloxicam and rofecoxib was improved using the biocompatible solvents such as ethanol, propylene glycol, glycerin, and PEG 400. Physico-chemical properties of the solvents such as intermolecular interactions and the ability of the solvent to form a hydrogen bond with the drug molecules were found to be the major factors involved in the dissolution of drugs. It was found that less polar solvents were found to increase solubility by greater extent, thus accentuating hydrophobic interaction mechanism. Among the solvent blends studied, water-PEG 400 had highest solubilization potential. Thus, the study generated an important dataset so as to compare effect of various cosolvents on the solubility of the drugs. Key words: Aqueous solubility, Meloxicam, Rofecoxib, Cosolvency. doi: 10.3329/dujps.v7i2.2166     Dhaka Univ. J. Pharm. Sci. 7(2): 119-126, 2008 (December)

scholarly journals Nanosuspension Technologies for Delivery of Poorly Soluble Drugs

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Roya Yadollahi ◽  
Krasimir Vasilev ◽  
Spomenka Simovic
Keyword(s):  
Aqueous Solubility ◽  
Drug Formulation ◽  
Preparation Methods ◽  
Administration Routes ◽  
Drug Molecules ◽  
Advanced Therapies ◽  
Poorly Soluble ◽  
Minimal Damage ◽  
Processing Techniques ◽  
Cancer Tissues

Poor aqueous solubility of some drug molecules is a major problem in drug formulation. Drug nanosuspensions emerged as one solution to delivering such hydrophobic drugs. Scaling down to nanoparticles enhances drug aqueous solubility and bioavailability by increasing drug surface area that comes into contact with biological media. Nanosuspensions that have attracted particular attention are those sterically stabilised by steric polymers such as polyethylene glycol (PEG) with a typical size range of 10–100 nm. These nanoparticles are capable of accumulating in targeted areas such as cancer tissues and infarct zones with minimal damage to healthy tissues. Nanosuspensions are often prepared by commercially available methods such as high pressure homogenization, media milling, emulsification, and melt emulsification. Solidification and surface modification methods are post-processing techniques used to add particular properties for advanced therapies. In this review, we firstly describe preparation methods for nanosuspensions. Secondly, we highlight typical characterization techniques. Finally, we describe several practical application of applications for drug delivery design and different administration routes such as parenteral, pulmonary, oral, and ocular.

scholarly journals Poly(ester amide)-Poly(ethylene oxide) Graft Copolymers: Towards Micellar Drug Delivery Vehicles

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gregory J. Zilinskas ◽  
Abdolrasoul Soleimani ◽  
Elizabeth R. Gillies
Keyword(s):  
Drug Delivery ◽  
Ethylene Oxide ◽  
Graft Copolymers ◽  
Nile Red ◽  
Biological Properties ◽  
Amphiphilic Copolymers ◽  
Drug Molecules ◽  
Poly Ethylene Oxide ◽  
Model Drug ◽  
Poly Ethylene

Micelles formed from amphiphilic copolymers are promising materials for the delivery of drug molecules, potentially leading to enhanced biological properties and efficacy. In this work, new poly(ester amide)-poly(ethylene oxide) (PEA-PEO) graft copolymers were synthesized and their assembly into micelles in aqueous solution was investigated. It was possible to tune the sizes of the micelles by varying the PEO content of the polymers and the method of micelle preparation. Under optimized conditions, it was possible to obtain micelles with diameters less than 100 nm as measured by dynamic light scattering and transmission electron microscopy. These micelles were demonstrated to encapsulate and release a model drug, Nile Red, and were nontoxic to HeLa cells as measured by an MTT assay. Overall, the properties of these micelles suggest that they are promising new materials for drug delivery systems.

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.

Enhancement of Solubility and Dissolution Rate of Poorly Water Soluble Drug using Cosolvency and Solid Dispersion Techniques

1970 ◽  
Vol 1 (4) ◽  
pp. 349-356
Author(s):  
Meka Lingam ◽  
Vobalaboina Venkateswarlu
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physicochemical Characterization ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
Peg 400 ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

The low aqueous solubility of celecoxib (CB) and thus its low bioavailability is a problem.    Thus, it is suggested to improve the solubility using cosolvency and solid dispersions techniques. Pure CB has solubility of 6.26±0.23µg/ml in water but increased solubility of CB was observed with increasing concentration of cosolvents like PEG 400, ethanol and propylene glycol. Highest solubility (791.06±15.57mg/ml) was observed with cosolvency technique containing the mixture of composition 10:80:10%v/v of water: PEG 400: ethanol. SDs with different polymers like PVP, PEG were prepared and subjected to physicochemical characterization using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), solubility and dissolution studies. These studies reveals that CB exists mainly in amorphous form in prepared solid dispersions of PVP, PEG4000 and PEG6000 further it can also be confirmed by solubility and dissolution rate studies. Solid dispersions of PV5 and PV9 have shown highest saturation solubility and dissolution rate

Self-microemulsion Technology for Water-insoluble Drug Delivery

2019 ◽  
Vol 15 (6) ◽  
pp. 576-588 ◽  
Author(s):  
Beibei Yan ◽  
Yu Gu ◽  
Juan Zhao ◽  
Yangyang Liu ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Aqueous Solubility ◽  
Delivery Systems ◽  
Poorly Soluble Drugs ◽  
New Chemical Entities ◽  
Poorly Soluble ◽  
Water Insoluble Drug ◽  
Semi Solid ◽  
Solidification Technology

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

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.

scholarly journals Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19)

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 460
Author(s):  
Amr El-Demerdash ◽  
Ahmed M. Metwaly ◽  
Afnan Hassan ◽  
Tarek Mohamed Abd El-Aziz ◽  
Eslam B. Elkaeed ◽  
...  
Keyword(s):  
In Silico ◽  
Active Sites ◽  
Specific Treatment ◽  
Aqueous Solubility ◽  
Maximum Tolerated Dose ◽  
Binding Energies ◽  
Log P ◽  
Binding Affinities ◽  
Structural Protein ◽  
Guanidine Alkaloids

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (ΔG = −8.05 kcal/mol), nucleocapsid phosphoprotein (ΔG = −6.49 kcal/mol), and nsp10 (ΔG = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (ΔG = −7.99 kcal/mol), spike glycoproteins (ΔG = −6.95 kcal/mol), and nucleocapsid phosphoprotein (ΔG = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and 13 showed promising docking, ADMET, toxicity and MD results which open the door for further investigations for them against SARS-CoV-2.

scholarly journals Synthesis, Characterization, and Evaluation of Radical Scavenging Ability of Ellagic Acid-Loaded Nanogels

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Gautam Behl ◽  
Monal Sharma ◽  
Saurabh Dahiya ◽  
Aruna Chhikara ◽  
Madhu Chopra
Keyword(s):  
Ellagic Acid ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Radical Scavenging ◽  
Aqueous Solubility ◽  
Loading Level ◽  
Human Cervical Cancer Cell ◽  
Poly Ethylene ◽  
Radical Scavenging Ability ◽  
Acid Loading

Ellagic acid (EA), a potential antioxidant phytochemical has low aqueous solubility and bioavailability. In this paper, encapsulation of ellagic acid has been carried out into the biodegradable disulfide crosslinked poly (ethylene glycol) PEO-based nanogels synthesized via AGET (activator generated electron transfer) ATRP (atom transfer radical polymerization), and their radical scavenging ability was evaluated. The encapsulation of the EA was carried out at two drug loading percentages, that is, 10 and 20 wt.% of the nanogels. 1,1-Diphenyl-2-picryldrazyl (DPPH) assay was utilized in order to assess the radical scavenging ability of the ellagic acid-loaded nanogels. A drug-loading level of about 2.5 wt.% was achieved with encapsulation efficiency of about 25% at 10 wt.% of the EA w.r.t nanogels, which was found to increase to about 4.7 wt.% with decreased encapsulation efficiency of 23.5% as EA content was increased to 20wt.% of the nanogels. Ellagic acid loading was found to be accompanied with increase in the size of the nanogels from144.6±39.52 nm for neat nanogels to217.8±105.5and633±160.1 nm at 2.5 and 4.7 wt.% drug loading level. The nanogels were found to be capable of scavenging radicals and biocompatible on human cervical cancer cell lines (HeLa cells) at appropriate concentrations.

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