Solubility Of Non-steroidal Anti-inflammatory Drugs Research Articles

An Evolving Role of Aqueous Piperazine to Improve the Solubility of Non-Steroidal Anti-Inflammatory Drugs

Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs−PIP salts, such as ibuprofen-piperazine (IBU−0.5PIP) salt, indomethacin−piperazine (IND−0.5PIP) salt, sulindac−piperazine (SUL−0.5PIP) salt, phenylbutazone−piperazine (PBZ−0.5PIP) salt, ketoprofen−piperazine (KPF-0.5PIP) salt and flurbiprofen−piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X−ray diffraction. Powder X−ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.

Mixed micellization of bile salts and transglycosylated stevia and enhanced binding and solubility of non-steroidal anti-inflammatory drugs using mixed micelle

This research investigated the efficacy of mixed micellar systems as an innovative chemical means of improving the binding properties of poorly water-soluble drugs. The formulations based on the mole fraction were used to prepare mixed micelles using anionic sodium deoxycholate (NaDC) or sodium cholate (NaC), and nonionic transglycosylated stevia (Stevia–G). Surface tension and dynamic light scattering (DLS) assessed the characteristic of the NaDC–Stevia–G and NaC–Stevia–G mixed micelles. Rubingh approach evaluated the interaction parameter (−βm), which demonstrated synergistic interaction between the anionic and non-ionic surfactant. Mixed micelle was used to assess the binding constant (Kb) and solubility of non-steroidal anti-inflammatory drugs, ethenzamide (ETZ), and ibuprofen (IBF). Kb values increased, but the mean occupancy (i) of ETZ and IBF per micelle decreased by increasing αStevia–G 0.1 to 0.9, predicting a shift in occupancy of drugs from Palisade to Stern layer. At αStevia–G 0.9 the maximum solubility of ETZ and IBF was 7.50 and 2.60 mmolL−1 for NaDC–Stevia–G and 5.60 and 1.70 mmolL−1 for NaC–Stevia–G. To get a better comprehension about micellization behavior and preferential interaction of the drugs under study, quantum chemical calculations and molecular dynamic (MD) simulations were performed. The MD analysis assessed that the poorly water-soluble drugs demonstrated strong binding in the presence of NaDC–Stevia–G as compared to NaC–Stevia–G mixed micelle. Ultimately, in pharmaceutical applications, mixed micelle of bile salts-Stevia-G can be used as an effective drug solubilizing agent.

Removal of Non-Steroidal Anti-Inflammatory Drugs from Aqueous Environments with Reusable Ionic-Liquid-based Systems.

In the current era of human life, we have been facing an increased consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Nevertheless, NSAIDs are not completely metabolized by humans and are further excreted into domestical effluents. Several studies have been showing that a wide variety of pharmaceuticals are present in water effluents and are thus a matter of serious concern in the public health. Although treatment plants use sophisticated technologies for pollutants/contaminants removal, none of these processes was particularly designed for NSAIDs. In this perspective, this work addresses the use of a liquid-liquid extraction approach, employing ionic liquids (ILs), for the removal of NSAIDs from aqueous media. In particular, aqueous biphasic systems (ABS) composed of ILs and aluminium-based salts, which are already used in water treatment plants, were tested for the removal of diclofenac, ibuprofen, naproxen and ketoprofen. With these systems, extraction efficiencies of NSAIDs up to 100% were obtained in a single-step. The recovery of NSAIDs from the IL medium and the recyclability of the IL-rich phase were then ascertained to guarantee the development of a more sustainable and cost-effective strategy. Based on the remarkable increase in the solubility of NSAIDs in the IL-rich phase (from a 300- to a 4100-fold when compared with pure water), water was then studied as an effective anti-solvent, and where single-step recovery percentages of NSAIDs from the IL-rich phase up to 91% were obtained. After the "cleaning" of the IL-rich phase by the induced precipitation of NSAIDs, the phase-forming components were recovered and reused in four consecutive cycles, with no detected losses on both the extraction efficiency and recovery of NSAIDs by induced precipitation. Finally, an integrated process is here proposed, which comprises the (i) removal of NSAIDs from aqueous media, (ii) the cleaning of the IL-rich phase by the recovery of NSAIDs by induced precipitation, and (iii) the phase-forming components recycling and reuse, aiming at unlocking new doors for alternative treatment strategies of aqueous environments.

Significantly improving the solubility of non-steroidal anti-inflammatory drugs in deep eutectic solvents for potential non-aqueous liquid administration

DESs can readily dissolve water-insoluble drugs to a high concentration and enhance the stability of dissolving drugs (e.g. aspirin).

Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural, cytotoxic, and drug release investigation

Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.

IUPAC-NIST Solubility Data Series. 102. Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

Solubility data are compiled and reviewed for 33 nonsteroidal anti-inflammatory drugs dissolved in neat organic solvents and in well-defined binary and ternary organic solvents. The compiled solubility data were retrieved primarily from the chemical and pharmaceutical literature covering the period from 1980 to the beginning of 2014.

Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Aqueous Solutions of Non-ionic Surfactants

The solubilities of two nonsteroidal anti-inflammatory (MELOXICAM and CELECOXIB) drugs, were determined in aqueous solutions of nonionic (Tween 20, Tween 80, Brij 30, Brij 35, Triton X 100, Triton X 114) surfactants. These surfactants have different numbers of oxyethylene units and their micelles showed different aggregation numbers. It is shown that these surfactants have different abilities to solubilize NSAIDs drugs. The solubilities of the drugs increased linearly with the increase in concentration of surfactants. The sizes of micelles remained constant with the addition of the drugs, except for Triton type surfactants in which case the size of the micelles decreased. It was observed that the number of oxyethylene units in the surfactants, aggregation number of the micelles and HLB play key roles in solubilizing the drugs.

Measurement and correlation for the solid solubility of non-steroidal anti-inflammatory drugs (NSAIDs) in supercritical carbon dioxide

The solubilities for three non-steroidal anti-inflammatory drugs (NSAIDs) of nabumetone, phenylbutazone and salicylamide in supercritical carbon dioxide were measured in this study using a semi-flow type apparatus. The experimental data were taken at 308.2, 318.2 and 328.2 K, over the pressure range from 10 to 22 MPa. The measured results were then correlated using semi-empirical equation presented by Chrastil, and that presented by Mendez-Santiago and Teja. With optimally fitted parameters, these two equations yielded satisfactory results where the average absolute relative deviation (AARD) was below 7%. Furthermore, the solid solubilities of these three compounds and seven other NSAIDs in supercritical carbon dioxide were correlated by applying the regular solution model coupled with a Flory–Huggins term. The solution model, which has fewer parameters than the semi-empirical equations, yielded comparable correlation results. The parameters in the solution model could be generalized for the specific group of NSAIDs. Finally, the predicted solubilities of 10 NSAIDs in supercritical carbon dioxide were demonstrated to be reliable.

Solubilization of non-steroidal anti-inflammatory drugs in the presence of tween series surfactants

The aqueous solubility of non-steroidal anti-inflammatory drugs (NSAIDs) Ketoprofen, Ibuprofen, Diflunisal and Naproxen were measured in the presence of the Tween series surfactants at 37°C. Results showed that the solubility of NSAIDs in the Tween solutions was approximately proportional to Tween concentration; the ability of Tween series surfactants to solubilize NSAIDs in the present study was Tween-80 > Tween-60 > Tween-40 > Tween-20; the order of increased solubility of NSAIDs in Tween series surfactants at a constant Tween series and concentration was Ibuprofen > Ketoprofen > Diflunisal > Naproxen. Under suitable conditions Tween series surfactants can be highly effective used to enhance the solubility of NSAIDs.

Dendrimers as Potential Drug Carriers. Part I. Solubilization of Non-Steroidal Anti-Inflammatory Drugs in the Presence of Polyamidoamine Dendrimers

The aqueous solubility of non-steroidal anti-inflammatory drugs (NSAIDs) Ketoprofen, Ibuprofen, Diflunisal and Naproxen were measured in the presence of the ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimers at 37 °C. The effect of concentration and generation of the PAMAM dendrimers has been investigated. Results showed that the solubility of NSAIDs in the PAMAM dendrimer solutions was approximately proportional to dendrimer concentration; the solubility of NSAIDs in higher generation PAMAM solutions was in fact higher that those in lower ones; the order of increased solubility of NSAIDs in PAMAM dendrimers at a constant dendrimer concentration and generation was Naproxen>Ketoprofen>Ibuprofen>Diflunisal. Under suitable conditions PAMAM dendrimers can be highly effective used to enhance the solubility of NSAIDs.

Parecoxib, Valdecoxib, and Cardiovascular Risk

Selective inhibitors of cyclooxygenase (COX)-21 depress prostacyclin (PGI2) but not COX-1–derived thromboxane A2. The effects of thromboxane A2 would be exaggerated during treatment with COX-2 inhibitors, potentially predisposing patients to heart attack and stroke.2 A randomized controlled trial in patients undergoing coronary artery bypass graft (CABG) surgery and receiving either placebo or 40 mg parecoxib (Dynastat; Pfizer), the intravenously administered prodrug of valdecoxib (Bextra; Pfizer), followed by oral valdecoxib 40 mg BID for 14 days, revealed a cluster of cardiovascular events.3 In a second study, one group received parecoxib/valdecoxib, another …