The effect of dry mixing on the apparent solubility of hydrophobic, sparingly soluble drugs

Mosharraf, Mitra; Nyström, Christer

doi:10.1016/s0928-0987(99)00043-3

Cited by 32 publications

(28 citation statements)

References 18 publications

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“…Previous groups have reported an increase in drug solubility when drug is co-ground with silicates (5,31). This increase has been attributed to the drug being in the amorphous state.…”

Section: Resultsmentioning

confidence: 97%

“…The variation in pH and the detection of different polymorphs made further interpretation of the results difficult. Previous studies reporting an increase in the solubility of poorly water soluble drugs by processing with silicates (4,5,31,32) have concluded that the increase is due to amorphization. However, pH variations and polymorphic transformations have not been explicitly accounted for in these studies.…”

Section: Effect Of Dissolution Mediummentioning

confidence: 97%

“…Using co-ground mixtures rather than neat amorphous indomethacin we report an increase in the MTC and MSC of co-ground amorphous indomethacin (in 0.1 N HCl where drug is unionized) with an increase in the amount of drug added to the dissolution medium. 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).…”

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 observed an increase in apparent solubility of griseofulvin when co-ground with glass beads (31) and an increase in what the authors' refer to as "apparent equilibrium solubility" of indomethacin when co-ground with Aerosil (5). In both studies water was used as a dissolution medium.…”

Section: Underlying Factors Affecting Peak (Mtc) and Plateau (Msc) Comentioning

confidence: 99%

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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

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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.

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“…Previous groups have reported an increase in drug solubility when drug is co-ground with silicates (5,31). This increase has been attributed to the drug being in the amorphous state.…”

Section: Resultsmentioning

confidence: 97%

Section: Effect Of Dissolution Mediummentioning

confidence: 97%

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

Section: Effect Of Quantity Of Excess Powdermentioning

confidence: 99%

Section: Underlying Factors Affecting Peak (Mtc) and Plateau (Msc) Comentioning

confidence: 99%

See 3 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

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Solubility and Dissolution Considerations for Amorphous Solid Dispersions

Ilevbare¹,

Xu²,

John³

et al. 2015

Pharmaceutical Sciences Encyclopedia

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This chapter presents differences between dispersions, amorphous materials, and crystalline forms, and discusses the impact of excipient selection, especially polymers. It provides guidance for solubility and dissolution testing of amorphous dispersions. Crystalline solids are mostly used in pharmaceutical drug formulations because of their physical and chemical stabilities. Amorphous solids are commonly described as condensed phases that lack the long‐range translational order typical of a crystalline solid, although the molecules may have short‐range order. The success of amorphous solids as a supersaturating dosage form depends on the choice of processing conditions to yield a pure amorphous solid with no or minimal crystallization of the amorphous drug during storage and upon dosing. The use of amorphous solid dispersions has become a well‐known strategy for inhibiting crystallization, as the amorphous solid dispersions can have increased physical stability over neat amorphous material.

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Development of Inhalable Nanocrystalline Solid Dispersion of Tranilast for Airway Inflammatory Diseases

Onoue

Aoki

Kawabata

et al. 2011

Journal of Pharmaceutical Sciences

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The effect of dry mixing on the apparent solubility of hydrophobic, sparingly soluble drugs

Cited by 32 publications

References 18 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

Solubility and Dissolution Considerations for Amorphous Solid Dispersions

Development of Inhalable Nanocrystalline Solid Dispersion of Tranilast for Airway Inflammatory Diseases

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