scholarly journals Solubility enhancement (Solid Dispersions) novel boon to increase bioavailability

2019 ◽  
Vol 9 (2) ◽  
pp. 583-590 ◽  
Author(s):  
Sandip R. Pawar ◽  
Shashikant D. Barhate
Keyword(s):  
Particle Size ◽  
Solid Dispersion ◽  
Water Solubility ◽  
New Technologies ◽  
Aqueous Media ◽  
Solubility Enhancement ◽  
Water Soluble ◽  
Formulation Development ◽  
Particle Size Reduction ◽  
Poorly Soluble

The solubility of a solute is the maximum quantity of solute that can dissolve in a certain quantity of solvent or quantity of solution at a specified temperature. Solubility is one of the important parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown. Solubility is essential for the therapeutic effectiveness of the drug, independent of the route of administration. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. Poorly soluble drugs are often a challenging task for formulators in the industry Conventional  approaches  for  enhancement  of  solubility  have  limited  applicability,  especially when  the  drugs  are  poorly  soluble  simultaneously  in  aqueous  and  in  non-aqueous  media. Drug with poor water solubility cause slow dissolution rates, generally show erratic and incomplete absorption leading to low bioavailability when administered orally. Solubilization may be affected by cosolvent water  interaction, micellar solubilization, reduction in  particle  size,  inclusion  complexes,  solid  dispersion,  and  change  in  polymorph.  Some  new technologies  are  also  available  to  increase  the  solubility  like  micro emulsion,  self-emulsifying drug  delivery  system  and  supercritical  fluid  technology. This present review details about the different approaches used for the enhancement of the solubility of poorly water-soluble drugs include particle size reduction, nanonization, pH adjustment, solid dispersion, complexation, co‐solvency, hydrotropy etc. The purpose of this article is to describe the techniques of solubilization for the attainment of effective absorption and improved bioavailability. Keywords: Solubility, Solubility Enhancement, bioavailability, solid dispersion, Solid Dispersion, Solubilization.

scholarly journals SOLUBILITY ENHANCEMENT OF POOR WATER SOLUBLE DRUGS BY SOLID DISPERSION: A REVIEW

2018 ◽  
Vol 8 (5) ◽  
pp. 44-49 ◽  
Author(s):  
SD Mankar ◽  
Punit R. Rach
Keyword(s):  
Solid Dispersion ◽  
High Throughput Screening ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Scale Up ◽  
Solubility Enhancement ◽  
Water Soluble ◽  
Formulation Development ◽  
Solubility Behavior ◽  
Poorly Water Soluble

The solubility behavior of drugs remains one of the most exigent aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased.  Among all the newly discovered chemical entities, about 40-45% drugs fail to reach market due to their poor water solubility. Because of solubility problem, bioavailability of drugs gets affected and hence solubility enhancement becomes necessary. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of drugs. Therefore, the application of this technique proves to be an important stratagem for pharmaceutical companies. However, the in - depth knowledge of the solid dispersion is desired for the scale up of formulation, from laboratory scale to industrial scale. There are various methods available to improve the solubility of the new drug in which solid dispersion emerged promising. A Solid dispersion generally composed of two components- the drug and the polymer matrix. Hence, this approach is expected to form a basis for the commercialization of many poorly water-soluble and water-insoluble drugs in their solid-dispersion formulations in the near future. This article reviews the various preparation techniques, carriers used, advantages and limitations of solid dispersions and compiles some of the recent advances. Keywords: Bioavailability, Solid Dispersion, Hydrophilic carriers, Polyethylene glycol.

scholarly journals SOLUBILITY ENHANCEMENT OF POORLY WATER SOLUBLE DRUGS BY VARIOUS TECHNIQUES

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Sakshi Minocha ◽  
Dr. Shilpa Pahwa ◽  
Dr. Vandana Arora
Keyword(s):  
Solid Dispersion ◽  
Water Solubility ◽  
Water Soluble ◽  
Formulation Development ◽  
Particle Size Reduction ◽  
Bioavailability Enhancement ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Poor Water Solubility

Solubility is not the ability to dissolve or thaw a substance; it may happen not only due to dissolution but also because of a chemical reaction. Solubility is the phenomenon of dissolution of solid in liquid phase to provide a homogenous system. Solubility is one of the vital factors for accomplishing desired concentration of drug in systemic circulation for pharmacological response. Low aqueous solubility is the major problem seen with formulation development of new chemical entities as well as for the generic development. With all new discovered chemical entities about 40% drugs are lipophilic and doesn’t shown therapeutic range due to their poor water solubility. Drug with poor water solubility shows slow dissolution rates, incomplete absorption and low bioavailability when taken orally. Drug solubility and bioavailability enhancement are the important in the formulation of pharmaceuticals. The Biopharmaceutics Classification System shows that Class II and IV drugs have low water solubility, poor dissolution, and low bioavailability. This review mentions different approaches used for the enhancement of the solubility of poorly water-soluble drugs that includes particle size reduction, pH adjustment, and solid dispersion. This describes the techniques of solubilizaton for the attainment of effective absorption and improved bioavailability. Keywords: Solubility, BCS classification, Bioavailability, Solid-dispersion.

scholarly journals Enhancement of solubility of Metaclopramide using solid dispersion technique with different carriers (HPβCD, PVP K-30)

2019 ◽  
Vol 9 (6) ◽  
pp. 17-22
Author(s):  
Moumita Paul ◽  
Pintu Sarkar ◽  
Riyanka Sengupta ◽  
Saikat Bhunia ◽  
Payal Jana ◽  
...  
Keyword(s):  
Oral Administration ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Water Soluble ◽  
Particle Size Reduction ◽  
First Pass Effect ◽  
Systemic Bioavailability ◽  
First Pass ◽  
Poorly Water Soluble ◽  
Poor Water Solubility

Modern drug discovery has led to the development of drug molecules that exhibit high lipophilicity and poor water solubility, which leads to problematic bioavailability. Approaches have thus been made to enhance dissolution of poorly water soluble drugs through modifications and creation of specific formulations. Metaclopramide is an antiemetic and gastroprokinetic agent, commonly used to treat nausea and vomiting. It is absorbed well after oral administration but a significant first pass effect in some human patients may reduce systemic bioavailability to 30%.The Metaclopramide base is thus modified from Metaclopramide hydrochloride to enhance solubility .This has been achieved by the formulating in solid dispersion since Metaclopramide is poorly water soluble. Though it is absorbed well after oral administration, a significant first pass effect in some patients reduces systemic bioavailability, which can cause adverse side effects. This solid dispersion has then been used through transdermal drug delivery. Enhancement of solubility of poorly water soluble drug by solid dispersion may be attributed to particles modified characters such as particle size reduction, improved wettability, higher porosity, decreased lattice energy, amorphous state. The main objective thus includes modification of drug Metaclopramide  hydrochloride to Metaclopramide base, preparation of solid dispersion of modified Metaclopramide  base drug which has poor water solubility, experimental analysis of Metaclopramide base drug and solid dispersion products with carriers. Keywords: solubility, Metaclopramide, solid dispersion, carriers, HPβCD, PVP K-30

scholarly journals Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hongxing Wang ◽  
Qigui Li ◽  
Sean Reyes ◽  
Jing Zhang ◽  
Lisa Xie ◽  
...  
Keyword(s):  
Particle Size ◽  
Solid Dispersion ◽  
Antimalarial Activity ◽  
Fold Increase ◽  
Water Soluble ◽  
Size Reduction ◽  
Particle Size Reduction ◽  
Physical Form ◽  
Poorly Water Soluble ◽  
Nanoparticle Formulation

Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

scholarly journals Formulation and Evaluation of Silymarin Microcrystals by In- Situ Micronization Technique

2019 ◽  
Vol 28 (1) ◽  
pp. 1-16
Author(s):  
Ala'a Dheia Noor ◽  
Eman B.H. Al-Khedairy
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Water Solubility ◽  
Ultrasonic Method ◽  
Volume Ratio ◽  
Water Soluble ◽  
Particle Size Reduction ◽  
Enhanced Solubility ◽  
Water Soluble Drugs

Silymarin (SM) is a plant extract obtained from Silybum marianum( milk thistle) . It is class II type drug according to  Biopharmaceutics Classification System with low bioavailability due to its low solubility. Micro/nanonization during crystallization, surface modification and crystal structure modification may improve the dissolution rate of poorly water-soluble drugs. The aim of this study was to increase the water solubility and dissolution rate of SM by in-situ micronization using solvent change either by stirring or ultrasonic method. Stabilizers like Gelatin, PVP-K30, HPMC15, Pulullan were used to stabilize the prepared ultrafine crystals. Effect of type and concentration of hydrophilic polymer, solvent: antisolvent volume ratio and the effect of ultrasonic irradiation were studied. The prepared  microcrystals were evaluated for their %yield,  water solubility, crystals structure by XRD,DSC, and SEM. Particle size and  dissolution rate were also tested . Silymarin microcrystals prepared by ultrasonic method and stabilized by 0.1%gelatin using 1:2 solvent: anti-solvent volume ratio showed the best results with particle size reduction from mean diameter of 1.5µm (untrated silymarin) to 0.43µm with uniform morphology and enhanced solubility and  dissolution.

Formulation Development and Evaluation of Novel Vesicular Carrier for Enhancement of Bioavailability of Poorly Soluble Drug

2020 ◽  
Vol 08 ◽  
Author(s):  
Sumit Sharma ◽  
Shailendra Bhatt ◽  
Vipin Saini
Keyword(s):  
Particle Size ◽  
Entrapment Efficiency ◽  
Water Soluble ◽  
Pharmacokinetic Parameters ◽  
Formulation Development ◽  
Carrier System ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
Lurasidone Hydrochloride

Background:: Niosomes are a vesicular carrier system comprised of a Nonionic surfactant bilayer surrounding an aqueous compartment. Niosomes are presumed to raise the intake of the poorly water-soluble drugs by M cells of Peyer's patches present in the intestine's lymphatic tissues, thereby avoiding the first-pass metabolism and increasing its oral bioavailability. Biodegradability, Nonimmunogenic nature, minimal side effects, low cost, good stability, and flexibility to incorporate hydrophilic and lipophilic drugs are other advantages of niosomes. Objective:: To formulate and evaluate a novel vesicular carrier system of a poorly soluble drug Lurasidone hydrochloride for the enhancement of its solubility and bioavailability Methods:: The thin-film hydration technique used to prepare Lurasidone hydrochloride loaded niosomes using different grades of nonionic surfactants like Brij, Span, and Tween. They evaluated for particle size, zeta potential, percent entrapment efficiency, in-vitro drug release, and in-vivo study. Results:: Niosomes comprised of Brij S-100 in drug: cholesterol: surfactant (1:1:1) showed particle size (1.15 ± 0.21 μm) and percent entrapment efficiency (97.02 ± 0.21%) and was selected for further studies. Various pharmacokinetic parameters like Cmax (281.27ng/ml), Tmax (5 h), and AUC (2640.197) were found to be significantly improved compared to plain drug solution. Conclusion:: The Niosomal formulation could be the promising drug delivery system for the controlled and sustained release of Lurasidone.

scholarly journals Fabrication of Submicrometer-Sized Meloxicam Particles Using Femtosecond Laser Ablation in Gas and Liquid Environments

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 996
Author(s):  
Eszter Nagy ◽  
Attila Andrásik ◽  
Tamás Smausz ◽  
Tibor Ajtai ◽  
Fruzsina Kun-Szabó ◽  
...  
Keyword(s):  
Particle Size ◽  
Laser Ablation ◽  
Water Solubility ◽  
Chemical Change ◽  
Pulsed Laser ◽  
Pulsed Laser Ablation ◽  
Water Soluble ◽  
Size Reduction ◽  
Distilled Water ◽  
Particle Size Reduction

In pharmaceutical development, more and more drugs are classified as poorly water-soluble or insoluble. Particle size reduction is a common way to fight this trend by improving dissolution rate, transport characteristics and bioavailability. Pulsed laser ablation is a ground-breaking technique of drug particle generation in the nano- and micrometer size range. Meloxicam, a commonly used nonsteroidal anti-inflammatory drug with poor water solubility, was chosen as the model drug. The pastille pressed meloxicam targets were irradiated by a Ti:sapphire laser (τ = 135 fs, λc = 800 nm) in air and in distilled water. Fourier transform infrared and Raman spectroscopies were used for chemical characterization and scanning electron microscopy to determine morphology and size. Additional particle size studies were performed using a scanning mobility particle sizer. Our experiments demonstrated that significant particle size reduction can be achieved with laser ablation both in air and in distilled water without any chemical change of meloxicam. The size of the ablated particles (~50 nm to a few microns) is approximately at least one-tenth of the size (~10–50 micron) of commercially available meloxicam crystals. Furthermore, nanoaggregate formation was described during pulsed laser ablation in air, which was scarcely studied for drug/organic molecules before.

scholarly journals Drug Solubility: Importance and Enhancement Techniques

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ketan T. Savjani ◽  
Anuradha K. Gajjar ◽  
Jignasa K. Savjani
Keyword(s):  
Crystal Engineering ◽  
Water Solubility ◽  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Formulation Development ◽  
Particle Size Reduction ◽  
New Chemical Entities ◽  
Poorly Soluble ◽  
Physical And Chemical ◽  
Site Of Absorption

Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.

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.

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.

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