Physicochemical Properties of Prostaglandin F2α (Tromethamine Salt): Solubility Behavior, Surface Properties, and Ionization Constants

Roseman, Theodore J.; Yalkowsky, Samuel H.

doi:10.1002/jps.2600621021

Cited by 67 publications

(30 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 In recent years, there has been growing interest in Tris as a promising pharmaceutical excipient because it is possible to increase the dissolution rate of drugs, to alter membrane permeability, to increase the bioavailability of sparingly soluble drugs, and to increase drug stability. [2][3][4][5][6][7][8][9][10][11][12] Tris salt of prostaglandin-F2 was selected as a raw material for its better crystallinity and purity. 2 Tris salt of some nonsteroidal anti-inflammatory agents showed decreased hygroscopicity and improved solubility and dissolution rates when compared with free acids and sodium salts.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6][7][8][9][10][11][12] Tris salt of prostaglandin-F2 was selected as a raw material for its better crystallinity and purity. 2 Tris salt of some nonsteroidal anti-inflammatory agents showed decreased hygroscopicity and improved solubility and dissolution rates when compared with free acids and sodium salts. 3 Tris salt of fosfomycin was reported to be more bioavailable than the calcium salt.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

2007

View full text Add to dashboard Cite

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1:3 (wt/wt) drug:PVP, 25% (wt/ wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at~129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 50 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

2007

View full text Add to dashboard Cite

show abstract

“…Unlike that of the well-studied surfactants, the solution chemistry of low-soluble amphiphilic ionizable drugs is often associated with the formation of sub-micellar aggregates, with examples such as amiodarone (pentamer, pH < 7), hydralazine (hexamer, pH < 7), pramoxine (octamer, pH < 8) (Bouligand et al, 1998;Bergström et al, 2004), and prostaglandin F2α (octamer, pH > 5) (Roseman and Yalkowsky, 1973). There are only a handful of other examples of sub-micellar aggregation (Higuchi et al, 1953;Bogardus and Blackwood, 1979;Serajuddin and Rosoff, 1984;Serajuddin and Jarowski, 1985;Fini et al, 1995;Zhu and Streng, 1996;Ledwidge and Corrigan, 1998;Jinno et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Phenothiazines solution complexity – Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

Pobudkowska

Ràfols

Subirats

et al. 2016

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The ionization constants (pK a ) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined at 25 and 37 o C. The pK a values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37 o C and methanol/water at 25 o C). The log S-pH profiles were measured at 24 h incubation time in 0.15 M phosphate buffers. The log S-pH "shape-template" method, which critically depends on accurate pK a values (determined independently of solubility data), was used to propose speciation models, which were subsequently refined by rigorous mass-action weighted regression procedure described recently. Differential scanning calorimetry (DSC), UV-visible spectrophotometry, potentiometric, and high performance liquid chromatography (HPLC) measurements were used to characterize the compounds. The intrinsic solubility (S 0 ) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25 o C were 0.5, 1.1, and 2.7 μg/mL (resp.). These values increased to 5.5, 9.2, and 8.7 μg/mL (resp.) at the physiological temperature. The enthalpies of solution for the latter compounds were exceptionally high positive (endothermic) values (99-152 kJ·mol -1 ).Cationic sub-micellar aggregates were evident (from the distortions in the log S-pH profiles) for chlorpromazine, fluphenazine, perphenazine, and trifluoperazine at 25 o C. The effects persisted at 37 o C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts.3

show abstract

“…All these effects can complicate the interpretation of the solubility data [9][10][11][12][13][14][15][16][17][18]. Such complexity may not be evident unless a full solubility -pH profile is measured, over a pH range containing the uncharged and charged forms of the drug, preferably at more than one solid-sample excess.…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, salt solubility analysis of data in the past had been done on a case by case basis, sometimes using incomplete explicit solubility equations. At times the impact of aggregation reactions had been recognized but not dealt with quantitatively, presumably because computational methods were not available at the time [9,10,16].…”

Section: Introductionmentioning

confidence: 99%

Salt Solubility Products of Diprenorphine Hydrochloride, Codeine and Lidocaine Hydrochlorides and Phosphates – Novel Method of Data Analysis Not Dependent on Explicit Solubility Equations

et al. 2013

View full text Add to dashboard Cite

show abstract

Physicochemical Properties of Prostaglandin F2α (Tromethamine Salt): Solubility Behavior, Surface Properties, and Ionization Constants

Cited by 67 publications

References 16 publications

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

Phenothiazines solution complexity – Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

Salt Solubility Products of Diprenorphine Hydrochloride, Codeine and Lidocaine Hydrochlorides and Phosphates – Novel Method of Data Analysis Not Dependent on Explicit Solubility Equations

Contact Info

Product

Resources

About