Exploration on the Drug Solubility Enhancement in Aqueous Medium with the Help of Endo-Functionalized Molecular Tubes: A Computational Approach

2021 ◽  
Author(s):  
Rabindranath Paul ◽  
Sandip Paul
Keyword(s):  
Pharmaceutical Industry ◽  
Aqueous Medium ◽  
Aqueous Solubility ◽  
Solubility Enhancement ◽  
Computational Approach ◽  
Drug Solubility ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Molecular Tubes

One major problem in the pharmaceutical industry is the aqueous solubility of newly developed orally administered drug candidates. More than 50 % of the newly developed drug molecules suffer from...

scholarly journals Basic Review: Solubility Enhancement by Using Various Approaches

2021 ◽  
Vol 68 (2) ◽  
Author(s):  
Baldha Krunal ◽  
Sanjay Savaliya ◽  
Payal N Vaja ◽  
Dr. Chetan H Borkhtaria
Keyword(s):  
Pharmaceutical Industry ◽  
Water Solubility ◽  
Development Stage ◽  
Solubility Enhancement ◽  
Therapeutic Action ◽  
Drug Solubility ◽  
Formulation Development ◽  
Bioavailability Enhancement ◽  
Screening Programs ◽  
New Chemical Entities

The solubility enhancement process of drugs plays a key role in the formulation development to achieve the bioavailability and therapeutic action of the drug at the target site. About 40% of the new chemical entities identified by pharmaceutical industry screening programs face numerous problems in the formulation and development stage because of poor water solubility and low bioavailability. Drug solubility and bioavailability enhancement are the important challenges in the field of formulation of pharmaceuticals.

A Computational Approach on the Stereoselective Binding of Peptides from Aqueous Medium with Endo-Functionalized Molecular Tubes

2021 ◽  
Author(s):  
Rabindranath Paul ◽  
Aritra Mitra ◽  
Sandip Paul
Keyword(s):  
Amino Acids ◽  
Aqueous Medium ◽  
Computational Approach ◽  
Enantiomerically Pure ◽  
Pharmaceutical Industries ◽  
Molecular Tubes

The need to obtain enantiomerically pure isomers of amino acids and peptides is often realized in the field of biology and in the pharmaceutical industries. Research is underway to devise...

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 ADME prediction with KNIME: A retrospective contribution to the second “Solubility Challenge”

ADMET & DMPK ◽  
2021 ◽  
Author(s):  
Gabriela Falcón-Cano ◽  
Christophe Molina ◽  
Miguel Angel Cabrera-Pérez
Keyword(s):  
Computational Models ◽  
Model Performance ◽  
Aqueous Solubility ◽  
Drug Solubility ◽  
Training Set ◽  
Drug Candidates ◽  
Creative Commons ◽  
Solid Form ◽  
Open Access Article

Computational models for predicting aqueous solubility from the molecular structure represent a promising strategy from the perspective of drug design and discovery. Since the first “Solubility Challenge”, these initiatives have marked the state-of-art of the modelling algorithms used to predict drug solubility. In this regard, the quality of the input experimental data and its influence on model performance has been frequently discussed. In our previous study, we developed a computational model for aqueous solubility based on recursive random forest approaches. The aim of the current commentary is to analyse the performance of this already trained predictive model on the molecules of the second “Solubility Challenge”. Even when our training set has inconsistencies related to the pH, solid form and temperature conditions of the solubility measurements, the model was able to predict the two sets from the second “Solubility Challenge” with statistics comparable to those of the top ranked models. Finally, we provided a KNIME automated workflow to predict the aqueous solubility of new drug candidates, during the early stages of drug discovery and development, for ensuring the applicability and reproducibility of our model. ©2021 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).  

scholarly journals Solubility EnhancementTechniques forPoorly Soluble Pharmaceuticals: A Review

2019 ◽  
Vol 7 (02) ◽  
pp. 09-16
Author(s):  
Jyoti Gupta ◽  
Anjana Devi
Keyword(s):  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Peptic Ulcers ◽  
Drug Solubility ◽  
Formulation Development ◽  
Drug Candidates ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
New Formulation ◽  
Rate Limiting

Among newly discovered chemical entities about 40% drugs are hydrophobic which are failed to reach market due to their low aqueous solubility. For orally administered drugs solubility is one of the rate limiting parameter to achieve their desired concentration in systemic circulation for pharmacological response.Drug efficacy can be limited due to poor aqueous solubility and some drugs also show side effects like gastric irritation, peptic ulcers,due to their poor solubility. Because of solubility problem of many drugs the bioavailability of them gets affected and hence solubility enhancement becomes challenging. The present review is devoted to various traditional and novel techniques for enhancing drug solubility to reduce the percentage of poorly soluble drug candidates eliminated from the new formulation development.

scholarly journals Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Shweta Gupta ◽  
Rajesh Kesarla ◽  
Abdelwahab Omri
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Aqueous Media ◽  
Aqueous Solubility ◽  
Delivery Systems ◽  
Water Soluble ◽  
The Self ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Water Soluble Drug

Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the challenges. In this review article, potential advantages and drawbacks of various conventional techniques and the newer approaches specifically the self-emulsifying systems are discussed. Various components of the self-emulsifying systems and their selection criteria are critically reviewed. The attempts of various scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, and so forth have also been included. Formulation of SEDDS is a potential strategy to deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility. The self-emulsifying system offers various advantages over other drug delivery systems having potential to solve various problems associated with drugs of all the classes of biopharmaceutical classification system (BCS).

Accurate predictions of aqueous solubility of drug molecules via the multilevel graph convolutional network (MGCN) and SchNet architectures

2020 ◽  
Vol 22 (41) ◽  
pp. 23766-23772 ◽  
Author(s):  
Peng Gao ◽  
Jie Zhang ◽  
Yuzhu Sun ◽  
Jianguo Yu
Keyword(s):  
Deep Learning ◽  
Pharmaceutical Industry ◽  
Aqueous Solubility ◽  
Molecular Properties ◽  
Convolutional Network ◽  
Drug Molecules

Deep learning based methods have been widely applied to predict various kinds of molecular properties in the pharmaceutical industry with increasingly more success.

A Free Energy Perturbation Approach to Estimate the Intrinsic Solubilities of Drug-like Small Molecules

2019 ◽  
Author(s):  
Sayan Mondal ◽  
Gary Tresadern ◽  
Jeremy Greenwood ◽  
Byungchan Kim ◽  
Joe Kaus ◽  
...  
Keyword(s):  
Solid State ◽  
Small Molecules ◽  
Three Dimensional ◽  
Aqueous Solubility ◽  
Computational Approach ◽  
Free Energy Perturbation ◽  
Perturbation Approach ◽  
Energy Perturbation ◽  
State Form ◽  
Good Agreement

<p>Optimizing the solubility of small molecules is important in a wide variety of contexts, including in drug discovery where the optimization of aqueous solubility is often crucial to achieve oral bioavailability. In such a context, solubility optimization cannot be successfully pursued by indiscriminate increases in polarity, which would likely reduce permeability and potency. Moreover, increasing polarity may not even improve solubility itself in many cases, if it stabilizes the solid-state form. Here we present a novel physics-based approach to predict the solubility of small molecules, that takes into account three-dimensional solid-state characteristics in addition to polarity. The calculated solubilities are in good agreement with experimental solubilities taken both from the literature as well as from several active pharmaceutical discovery projects. This computational approach enables strategies to optimize solubility by disrupting the three-dimensional solid-state packing of novel chemical matter, illustrated here for an active medicinal chemistry campaign.</p>

The Position of ADME Predictions in Multi-Objective QSAR

2021 ◽  
Vol 6 (1) ◽  
pp. 1-8
Author(s):  
Anna Tsantili-Kakoulidou
Keyword(s):  
Drug Efficacy ◽  
Clinical Development ◽  
Efficacy And Safety ◽  
Huge Amount ◽  
Multi Objective ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Qsar Models ◽  
Adme Properties ◽  
Single Objective

ADME properties and toxicity predictions play an essential role in prioritization and optimization of drug molecules. According to recent statistics, drug efficacy and safety are principal reasons for drug failure. In this perspective, the position of ADME predictions in the evolution of traditional QSAR from the single objective of biological activity to a multi-task concept is discussed. The essential features of ADME and toxicity QSAR models are highlighted. Since such models are applied to prioritize existing or virtual project compounds with already established or predicted target affinity, a mechanistic interpretation, although desirable, is not a primary goal. However, a broad applicability domain is crucial. A future challenge with multi-objective QSAR is to adapt to the realm of big data by integrating techniques for the exploitation of the continuously increasing number of ADME data and the huge amount of clinical development endpoints for the sake of efficacy and safety of new drug candidates.

scholarly journals Improving Physicochemical Properties of Repaglinide Through Pharmaceutical Adduct Formation

2020 ◽  
Vol 8 (1) ◽  
pp. 31-37
Author(s):  
Sharen Gill ◽  
Poonam Arora
Keyword(s):  
Pharmaceutical Industry ◽  
Physicochemical Properties ◽  
Physicochemical Characteristics ◽  
Adduct Formation ◽  
Drug Solubility ◽  
Salt Formation ◽  
Slow Evaporation ◽  
Dissolution Studies ◽  
Hypoglycemic Agent ◽  
Standard Techniques

Background: Many formulation strategies are presently in development in pharmaceutical industry. However, the formation of pharmaceutical adducts is considered to be the most appropriate technique for improving the drug solubility and dissolution as no chemical bond changes are involved in this technique.Purpose: This technique is highly used for compounds which are not able to give viable formulation products with standard techniques such as salt formation and polymorph generation. In the present study, this method is applied to repaglinide, which is an hypoglycemic agent, with compromised solubility. Methods: The adducts were prepared by slow evaporation method and characterized using DSC, FTIR and PXRD studies. The solubility and dissolution studies were carried out to determine the increased solubility of drug in adducts. The drug amount interacted with coformers has also been determined. Results: The present study demonstrates the improvement in solubility and thus dissolution of repaglinide in adducts.Conclusion: The adducts formed in the present study can be further exploited to prepare formulation of repaglinide adducts with better physicochemical characteristics.

Sign in / Sign up

Export Citation Format

Share Document