scholarly journals Nanosuspension of Poorly Soluble Anti-Diabetic Drug for Enhancement of Solubility and Dissolution

2021 ◽  
Vol 23 (11) ◽  
pp. 516-541
Author(s):  
Parivallal Padmanaban ◽  
◽  
Punit R. Rachh ◽  
Keyword(s):  
Hydrophobic Interactions ◽  
Aqueous Dispersion ◽  
Fold Increase ◽  
Pluronic F127 ◽  
Drug Dissolution ◽  
Poly Vinyl Alcohol ◽  
Renal Tubules ◽  
Formulation Development ◽  
Poorly Soluble ◽  
Nano Formulation

Canagliflozin is an anti-diabetic drug used in the adjuvant therapy for type-II diabetes as the inhibitor of sodium‐glucose co‐transporter-2 in the renal tubules. The poor solubility and permeability of the drug show limitations in the formulation development and therapeutic plasma concentration. The objective of the work was to improve the solubility and dissolution of the BCS class IV drug through surfactant stabilized nanosuspension formulation. Nanoparticles were developed by Nano precipitation-solvent evaporation method using Poly vinyl alcohol and Pluronic as surfactants at 1%, 3% and 5% concentration. Formulation optimized with Pluronic exhibited nano size particles (81-117 nm) with monodisperse nature and high stability zeta potential. The nanosuspension prepared using 1% and 3% Pluronic F127 showed 2-fold and 5- fold increase in the drug dissolution compared to the pure drug aqueous dispersion. The drug and surfactant exhibited mild interactions due to hydrogen bonding and hydrophobic interactions as confirmed by the FTIR and TG-DSC analysis, which favoured the formation of stable nanoparticles. The SEM proved the formation of smooth surface spherical shaped nanoparticles. Hence, the development of Canagliflozin nano-formulation was evidenced be an optimized approach to enhance the dissolution of the drug.

scholarly journals Bioavailability Enhancement Techniques for Poorly Soluble Drugs: A Review

2020 ◽  
Vol 8 (2) ◽  
pp. 75-78
Author(s):  
Ravi Gupta ◽  
Vidhi Jain ◽  
Jagdish Chand Nagar ◽  
Aadil Ansari ◽  
Kapil Sharma ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
New Drugs ◽  
Drug Dissolution ◽  
Formulation Development ◽  
Bioavailability Enhancement ◽  
Novel Technologies ◽  
Drug Products ◽  
Bcs Class Ii ◽  
Poorly Soluble ◽  
Extent Of Absorption

Bioavailability is defined as the rate and extent of absorption of unchanged drug from its dosage form. The oral bioavailability of drugs with poor solubility and reasonable permeability is limited by the drug dissolution step from drug products. Low aqueous solubility is the major problem encountered with formulation development of new drugs. The article briefly highlights traditional and novel techniques that are used for solubility enhancement of BCS Class II drugs are discussed in this article. The Traditional techniques include use of co-solvents, hydrotrophy, micronization, change in dielectric constant of solvent, amorphous forms, chemical modification of drug, use of surfactants etc. Novel technologies are size reduction technologies, lipid based delivery system, micellar technologies, solid dispersion and many more.    

scholarly journals Formulation development and optimization of fast dissolving film containing carvedilol nanocrystals for improved bioavailability

2018 ◽  
Vol 8 (6) ◽  
pp. 74-81 ◽  
Author(s):  
Anju Sharma ◽  
P Sriganesan
Keyword(s):  
Drug Dissolution ◽  
Formulation Development ◽  
Casting Method ◽  
Box Behnken Design ◽  
Design Expert ◽  
Dissolution Properties ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
High Pressure Homogenizer

In this work, fast dissolving films (FDF) were prepared using nanocrystal formulations in order to optimise dissolution properties of lipophilic, poorly soluble drug Cavedilol. Drug nanocrystals are crystals with a size in the nanometer range, meaning that they are nanoparticles with a crystalline character. Carvedilol nanosuspensions were prepared using a high-pressure homogenizer, and then encapsulated in to films by solvent casting method using polymers such as maltodextrin and PVA in different concentrations. Propylene glycol used as a plasticizer. This study aimed to develop and evaluate the formulation of FDF containing Carvedilol nanocrystals for enhanced bioavailability and better compliance. The formulation of FDF was optimized by Box-Behnken Design (BBD) (design expert 11.03).In this design, 13 formulas were performed. One of the formula were suggested by design expert desirability = 1. Keywords: Carvedilol, Nanocrystal, FDF, Box-bhenken optimization, in-vitro drug dissolution study,

Insight into Delivery Approaches for Biopharmaceutics Classification System Class II and IV Drugs

2020 ◽  
Vol 10 (4) ◽  
pp. 255-277
Author(s):  
Shashank Chaturvedi ◽  
Raghav Mishra
Keyword(s):  
Class Ii ◽  
Crystal Habit ◽  
Extensive Literature ◽  
Formulation Development ◽  
Particle Size Reduction ◽  
Bioavailability Enhancement ◽  
Poor Solubility ◽  
Biopharmaceutics Classification System Class ◽  
Poorly Soluble ◽  
Physical And Chemical

: Formulation development of BCS Class II and IV drugs is a challenging task due to their poor solubility and permeability issue. : An extensive literature survey was conducted to explore the relevant pharmaceutical approaches that have been used for solving the issue of poor solubility and permeability in the recent past. : It has been found that a plethora of approaches have been investigated for addressing the issue of poor solubility and or permeability. These include physical modifications (modification of crystal habit, particle size reduction, complexation, polymorphism and drug dispersion in carriers), chemical modifications (salt formation), and formulation modifications (Nanotechnology-based approaches and hydrotropy). : The physical and chemical modification approaches can be effectively used to enhance the solubility and dissolution rate of poorly soluble drugs, but the additional problem of poor permeability has been better addressed by lipid-based drug delivery systems. As the latter presents the drug in the solubilized state, bypass first-pass effects, circumvent the effect of Para-glycoprotein mediated efflux of drugs, hence contributing to overall bioavailability enhancement.

Electrically Triggered Transdermal Drug Delivery Utilizing Poly(Acrylamide)-graft-Guar Gum: Synthesis, Characterization and Formulation Development

2019 ◽  
Vol 3 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Ravindra P. Birajdar ◽  
Sudha S. Patil ◽  
Vijaykumar V. Alange ◽  
Raghavendra V. Kulkarni
Keyword(s):  
Drug Delivery ◽  
Electric Current ◽  
Transdermal Drug Delivery ◽  
Guar Gum ◽  
Fold Increase ◽  
Formulation Development ◽  
Neutralization Equivalent ◽  
Electric Stimulus ◽  
Drug Permeation ◽  
Transdermal Drug Delivery Systems

Objective: The study aimed to prepare electrically-triggered transdermal drug delivery systems (ETDS) using electrically responsive polyacrylamide-graft-gaur gum (PAAm-g-GaG) copolymer. Methods: The PAAm-g-GaG copolymer was synthesized by adopting free radical polymerization grafting method. This PAAm-g-GaG copolymer hydrogel acts as a drug reservoir and blend films of Guar Gum (GaG) and Polyvinyl Alcohol (PVA) were included as Rate Controlling Membranes (RCM) in the system. The PAAm-g-GaG copolymer was characterized by FTIR, neutralization equivalent values, thermogravimetric analysis and elemental analysis. Results: On the basis of results obtained, it is implicit that the drug permeation decreased with an increase in the concentration of glutaraldehyde and RCM thickness; while drug permeation rate was increased with increasing applied electric current strength from 2 to 8 mA. A two fold increase in flux values was observed with the application of DC electric current. An increase in drug permeation was witnessed under on condition of electric stimulus and permeation was decreased when electric stimulus was "off". The skin histopathology study confirmed the changes in skin structure when electrical stimulus was applied. Conclusion: The electrically-sensitive PAAm-g-GaG copolymer is a useful biomaterial for transdermal drug delivery application.

scholarly journals Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Lise Vandevivere ◽  
Maxine Vangampelaere ◽  
Christoph Portier ◽  
Cedrine de Backere ◽  
Olaf Häusler ◽  
...  
Keyword(s):  
Dissolution Kinetics ◽  
Wet Granulation ◽  
Continuous Manufacturing ◽  
Formulation Development ◽  
Granulation Process ◽  
Low Viscosity ◽  
Twin Screw ◽  
Poorly Soluble ◽  
Selection For ◽  
The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

Thermodynamics and acoustic effects of quercetin on micellization and interaction behaviour of CTAB in different hydroethanol solvent systems

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Vikrant Abbot ◽  
Poonam Sharma
Keyword(s):  
Pharmaceutical Industry ◽  
Hydrophobic Interactions ◽  
Chemical Properties ◽  
Formulation Development ◽  
Surfactant Interactions ◽  
Physico Chemical ◽  
Ultrasonic Sound ◽  
Apparent Molar Compressibility ◽  
Solvent Systems ◽  
Thermoacoustic Properties

AbstractFlavonoids amongst the class of secondary metabolites possess numerous health benefits, are known for its use in pharmaceutical industry. Quercetin, a flavonoid has more prominent medical advantages however its utilization is constrained because of various instability and insolubility issues and therefore, taken into consideration for studying its physico-chemical properties. In view of that, the thermodynamic and thermoacoustic properties of quercetin were examined in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB) at different hydroethanolic concentrations and temperatures. The conductivity studies were used to calculate change in enthalpy (∆Hom), change in entropy (∆Som) and change in Gibbs free Energy (∆Gom) of micellization. The interactions between quercetin and CTAB were found to be endothermic, entropically controlled and spontaneous. Further, ultrasonic sound velocity and density studies were carried out and utilized for the calculation of thermoacoustic parameters i.e. apparent molar volume and apparent molar compressibility. Thermoacoustic properties revealed that at higher surfactant concentration, hydrophobic interactions are dominant. The results suggested that the flavonoid-surfactant interactions in hydroethanolic solutions is more favourable as compared with aqueous solution. Overall, the data is favourable for the framework to be used for detailing advancement, drug development, drug industry, pharmaceutical industry, medical administration and formulation development studies.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 101 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

Temperature Responsive Gels Based on Pluronic F127 and Poly(vinyl alcohol)

2011 ◽  
Vol 50 (7) ◽  
pp. 4199-4206 ◽  
Author(s):  
Maria Bercea ◽  
Raluca Nicoleta Darie ◽  
Loredana Elena Niţă ◽  
Simona Morariu
Keyword(s):  
Vinyl Alcohol ◽  
Pluronic F127 ◽  
Poly Vinyl Alcohol ◽  
Temperature Responsive ◽  
Responsive Gels

Expression of bcl-2 and bax in regenerating rat renal tubules following ischemic injury

1997 ◽  
Vol 272 (5) ◽  
pp. F640-F647 ◽  
Author(s):  
D. P. Basile ◽  
H. Liapis ◽  
M. R. Hammerman
Keyword(s):  
Proximal Tubule ◽  
Ischemic Injury ◽  
Fold Increase ◽  
Renal Tubules ◽  
Proximal Tubule Cells ◽  
Protein Levels ◽  
Bax Protein ◽  
Adult Kidney ◽  
Predictable Pattern

To define potential roles for bcl-2 and bax in adult kidney as regulators of regeneration, their expressions were characterized postischemic injury. A 2.1-fold increase in levels of renal bcl-2 mRNA occurred within 24 h of injury relative to levels in kidney of sham-operated control rats. The levels of bcl-2 mRNA remained elevated for 3 days but returned to baseline by day 5 postischemia. In situ hybridization of kidneys from sham-operated rats demonstrated faint expression of bcl-2 mRNA localized diffusely throughout the nephron. After renal injury, the expression of bcl-2 mRNA was markedly enhanced in regenerating proximal tubule cells relining the basement membrane. Immunohistochemistry showed a similar localization for bcl-2 protein. Levels of bax mRNA in kidney were elevated beginning at 24 h postischemia and remained elevated for 7 days postinjury. Bax mRNA and bax protein were colocalized to regenerating proximal tubules postischemia and were prominently expressed in papillary proliferations. We conclude that the expressions of bcl-2 and bax in kidney are enhanced in a predictable pattern following acute ischemic injury. Our findings suggest that these regulators of apoptosis play key roles in the process of repair of the damaged proximal tubule postischemia.

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