Solubility of E2050 at Various pH: A Case in Which Apparent Solubility is Affected by the Amount of Excess Solid

Wang, Zeren; Burrell, Lana S.; Lambert, William J.

doi:10.1002/jps.10107

Cited by 33 publications

(20 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study reports an increase in the solubility of drugs (mixed with glass beads or sodium chloride) with an increase in the amount of drug (31). However, contradictory to the other two reports (33,34), the solubility for the corresponding crystalline drugs was reported to be independent of the amount of excess (31). As the amount of co-ground amorphous indomethacin in dissolution studies was increased, there was a proportional increase in the amount of Neusilin US2.…”

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

“…The decline in the concentration is due to crystallization of indomethacin. Others have reported on the effect of amount of excess solid on solubility (31,33,34). One such study was specific for salt forms (mono and dihydrochloride) of an experimental basic drug (E2050) (33).…”

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

“…Others have reported on the effect of amount of excess solid on solubility (31,33,34). One such study was specific for salt forms (mono and dihydrochloride) of an experimental basic drug (E2050) (33). An increase in the amounts of excess of dihydrochloride salt lowered its solubility due to precipitation of the lower solubility monohydrochloride salt (in pH regions where solubility is controlled by monohydrochloride salt).…”

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

See 2 more Smart Citations

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Bahl

Bogner

2008

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The solubility advantage of indomethacin amorphized by co-grinding with Neusilin US2 in various media was investigated. Physical mixtures of γ-indomethacin and Neusilin US2 (in the ratios 1:1, 1:4 and 1:5) were amorphized at room temperature employing 75% RH in a porcelain jar mill using zirconia balls. The crystallinity of the samples was determined using ATR-FTIR and PXRD. The solubility and dissolution profiles of co-ground powders and crystalline counterparts were evaluated in 0.1 N HCl, water and phosphate buffer (pH 6.8) in a USP type II dissolution apparatus at 250 rpm and 37°C. Very high concentrations of dissolved indomethacin as compared to the solubility of γ-indomethacin (~500 times in water and~3.7 times in phosphate buffer) were attained. However, the presence of other polymorphs detected by PXRD and a change in the pH of the medium made interpretation of the results difficult. In 0.1 N HCl the solubility (i.e., the peak in a concentration versus time plot) of the amorphized drug in a 1:5 ratio with Neusilin increased to 109 times the solubility of crystalline γ-indomethacin alone. An increase in amount of drug and Neusilin in the same ratio added to the dissolution medium also increased peak and plateau dissolution concentrations. The presence of silicic acid and ions (Mg 2+ and Al 3+ ) in the dissolution media were found to cause the increase in the plateau concentration of indomethacin. Amorphization alone does not account for all of the dissolution enhancement; acidity, ions, and silicic acid are major contributors to dissolution enhancement.

show abstract

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

See 1 more Smart Citation

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Bahl

Bogner

2008

AAPS PharmSciTech

View full text Add to dashboard Cite

show abstract

“…The added amount should be enough to make a saturated solution in equilibrium with the solid phase. In case of acidic or basic drugs dissolved in an un-buffered solubility medium, further addition of the solid could change pH of the solution and consequently the solubility of the drug (Wang et al, 2002;Kawakami et al, 2005;Jouyban and Soltanpour, 2010). Depending on the dissolution rate and type of agitation used, the equilibration time between the dissolved drug and the excess solid could be varied.…”

Section: Shake Flask Methodsmentioning

confidence: 99%

Experimental and Computational Methods Pertaining to Drug Solubility

Jouyban¹,

Fakhree²

2012

Toxicity and Drug Testing

View full text Add to dashboard Cite

“…The constants in the solubility calculation are iteratively refined with respect to the fixed value of I ref , but are continuously adjusted in the mass balance calculation to the variable ionic strength, I, for each value of pH. The procedure includes the calculation of the activity coefficients using hydration theory proposed by Stokes and Robinson (1948), and has been detailed elsewhere (Wang et al, 2002;Völgyi et al, 2013).…”

Section: Ionic Strength Dependence Of Constants: Pk a Aggregation mentioning

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

Solubility of E2050 at Various pH: A Case in Which Apparent Solubility is Affected by the Amount of Excess Solid

Cited by 33 publications

References 10 publications

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Experimental and Computational Methods Pertaining to Drug Solubility

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

Contact Info

Product

Resources

About