Drug Solubility: Importance and Enhancement Techniques

Savjani, Ketan; Anuradha, G; Savjani, Jignasa

doi:10.5402/2012/195727

Cited by 1,266 publications

(1,154 citation statements)

References 47 publications

Supporting

Mentioning

1,110

Contrasting

Unclassified

Order By: Relevance

“…Thermodynamic solubility is a parameter considered throughout the drug discovery process, from lead optimization to formulation. In recent years, it has been suggested that up to 40% of new drug molecules are effectively insoluble 15 and up to 75% are classified as having low solubility by the Biopharmaceutics Classification System (BCS). 16,9 At the lead optimization stage, it is not practical to carry out experimental determinations of thermodynamic solubility on large libraries of compounds.…”

Section: Introductionmentioning

confidence: 99%

Are the Sublimation Thermodynamics of Organic Molecules Predictable?

McDonagh

Palmer

Mourik

et al. 2016

J. Chem. Inf. Model.

View full text Add to dashboard Cite

We compare a range of computational methods for the prediction of sublimation thermodynamics (enthalpy, entropy and free energy of sublimation). These include a model from theoretical chemistry that utilizes crystal lattice energy minimization (with the DMACRYS program) and QSPR models generated by both machine learning (Random Forest and Support Vector Machines) and regression (Partial Least Squares) methods. Using these methods we investigate the predictability of the enthalpy, entropy and free energy of sublimation, with consideration of whether such a method may be able to improve solubility prediction schemes. Previous work has suggested that the major source of error in solubility prediction schemes involving a thermodynamic cycle via the solid state is in the modeling of the free energy change away from the solid state. Yet contrary to this conclusion other work has found that the inclusion of terms such as the enthalpy of sublimation in QSPR methods 2 does not improve the predictions of solubility. We suggest the use of theoretical chemistry terms, detailed explicitly in the methods section, as descriptors for the prediction of the enthalpy and free energy of sublimation. A dataset of 158 molecules with experimental sublimation thermodynamics values and some CSD refcodes has been collected from the literature and is provided with their original source references.

show abstract

Section: Introductionmentioning

confidence: 99%

Are the Sublimation Thermodynamics of Organic Molecules Predictable?

McDonagh

Palmer

Mourik

et al. 2016

J. Chem. Inf. Model.

View full text Add to dashboard Cite

show abstract

“…BCS class II drugs are characterized by high membrane permeability but low aqueous solubility therefore; there is a low drug concentration gradient between the gut and the blood vessels limiting drug transport and oral bioavailability. The poor solubility of drugs has always been a major problem in pharmaceutical development and this problem is now more prevalent with more than 40 % of the new chemical entities being practically insoluble in water or lipophilic in nature [3][4][5][6][7]. As dissolution rates are typically the rate-limiting step for bioavailability, especially for poorly soluble drugs, enhancement of solubility is vital to attaining suitable systemic concentrations for therapeutic effect [8].…”

Section: Introductionmentioning

confidence: 99%

“…This enhancement of dissolution rate by size reduction is due to the fact that solubility of drugs in intrinsically related to particle size of the drug [7]. As the particle size of the drug is reduced, the surface area available for solvation also increases.…”

Section: Introductionmentioning

confidence: 99%

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions

Adebisi

Kaialy

Hussain

et al. 2016

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions, Colloids and Surfaces B: Biointerfaces http://dx.doi.org/10. 1016/j.colsurfb.2016.07.032 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 4. GLU improved the handling of PXM as it significantly reduced its charge in all the spray dried formulations. Technique could be used to determine appropriate formulations that improve handling AbstractThis work explores the use of both spray drying and D-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging was also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM.XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5 µm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5 nC/g for untreated material and -7.5 versus 3.1 nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1 -0.3 3 nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM.

show abstract

“…Poor bioavailability of the drug is a major disadvantage of oral drug delivery due to low aqueous solubility and low drug permeability (Savjani et al, 2012). The poorly water soluble drug indicate low absorption and bioavailability is often controlled by the rate of dissolution of the drug in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

PREPERATION AND CHARACTERIZATION OF Β-Cyclodextrin INCLUSION COMPLEXES ORAL TABLETS CONTAINING POORLY WATER SOLUBLE GLIMIPIRIDE USING FREEZE DRYING METHOD

Syukri

Fernenda,

Utami

et al. 2015

Indonesian J. Pharm.

View full text Add to dashboard Cite

Glimepiride is an oral antidiabetic drugs which is practically insoluble in water. The formation of β-cyclodextrin inclusion complex was able to increase the solubility of glimepiride. This study aim to prepare, characterize and formulation of inclusion complex tablets in order to meet the requirement in Pharmacopeia. The inclusion complex were prepared in a molar ratio of 1:1 and 1:2 by freeze drying method, after that characterized include FTIR spectroscopy and scanning electro microscope (SEM). Further, it was formulated into tablets by direct compression technique using primogel and crospovidone as super disintegrants. The tablets were evaluated include weight uniformity, hardness, friability, disintegration, and dissolution. The dissolution studies of inclusion complex were performed by using USP II apparatus. The result of FTIR and SEM provided evidence of the formation of complexes after utilizing freeze-drying methods. The tablet evaluation containing inclusion complex glimepiride-β cyclodextrin with primogel and cropovidone as disintegrant showed that increased concentration of disintegrant will increase disintegration time of the tablets. All of formulas meet the requirements in the Pharmacopoeia. The inclusion complex of glimepiride-β cyclodextrin successfully used for enhancing the solubility of glimepiride and the tablets meet the requirement in Pharmacopeia.

show abstract

Drug Solubility: Importance and Enhancement Techniques

Cited by 1,266 publications

References 47 publications

Are the Sublimation Thermodynamics of Organic Molecules Predictable?

Are the Sublimation Thermodynamics of Organic Molecules Predictable?

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions

PREPERATION AND CHARACTERIZATION OF Β-Cyclodextrin INCLUSION COMPLEXES ORAL TABLETS CONTAINING POORLY WATER SOLUBLE GLIMIPIRIDE USING FREEZE DRYING METHOD

Contact Info

Product

Resources

About