Contribution of solid-state properties to the aqueous solubility of drugs

Wassvik, Carola M.; Holmén, Anders; Bergström, Christel A S; Zamora, Ismael; Artursson, Per

doi:10.1016/j.ejps.2006.05.013

Cited by 126 publications

(101 citation statements)

References 35 publications

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“…The log P values of 2.04 and 0.68 were obtained for GLZ and Na-GLZ, respectively (RSD less than 3.1%). These results agree with the previously published data for the partition coefficient of gliclazide (7,30). Accordingly, the salt form is approximately 20 times more hydrophilic than the untreated form.…”

Section: Solubility and Partition Coefficientsupporting

confidence: 83%

“…Six tablets of each formulation were placed one in each vessel containing 900 mL of the test medium. Samples (2 mL) were withdrawn at predetermined time points (10,20,30,45,60, and 120 min), and the volume withdrawn was taken into consideration when calculating the percentage release of GLZ or Na-GLZ in the remaining volume of test medium. Filtration of samples was performed in situ via resident probes to which polyethylene filters were connected and designed to be left in the dissolution vessel for the duration of the test.…”

Section: Dissolution Testsmentioning

confidence: 99%

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Improvement of Dissolution Rate of Gliclazide Through Sodium Salt Formation

El-Sabawi¹,

Hamdan²

2014

Dissolution Technol.

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Gliclazide is a hypoglycemic agent exhibiting to some extent inadequate and variable absorption as a consequence of poor aqueous solubility and slow dissolution rates. A sodium salt of gliclazide was prepared and investigated for solubility and dissolution properties in comparison to untreated gliclazide. The salt was formed by adding equimolar amounts of gliclazide and sodium hydroxide in an aqueous-ethanolic phase. To confirm salt formation, sodium gliclazide was fully characterized by spectroscopy, differential scanning calorimetry, and potentiometric titration. Furthermore, solubility and in vitro dissolution studies of formulated tablets were performed at pH values of 1.2, 4.5, and 6.8. Sodium gliclazide demonstrated a significant increase in solubility at pH values of 4.5 and 6.8. The most apparent increase was achieved in unbuffered distilled water with a 235-fold higher solubility. Moreover, sodium gliclazide showed an enhancement in the dissolution rate in all tested media, but most significantly at pH 4.5 and 6.8. The highest difference (60%) in dissolution rate between gliclazide and its sodium salt was obtained at pH 6.8 at 30 min.The sodium salt of gliclazide presents improved solubility and drug dissolution, therefore limiting the possibility of variable absorption and improving the onset of action with potential enhancement in its overall bioavailability.

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Section: Solubility and Partition Coefficientsupporting

confidence: 83%

Section: Dissolution Testsmentioning

confidence: 99%

Improvement of Dissolution Rate of Gliclazide Through Sodium Salt Formation

El-Sabawi¹,

Hamdan²

2014

Dissolution Technol.

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“…Clog P classifies the drug as BCS (Biopharmaceutics Classification System) class IV and log P values as BCS class II (TSRL Inc. BCS Classification System; http://69.20.123.154/services/bcs/search.cfm). pK a of gliclazide is 6.9 and intrinsic solubility (log S o , expressed as the average log molar concentration ±1 standard deviation) is -4.07 ± 0.03 (4). The aqueous solubility of gliclazide at 37°C is 55 mg mL -1 (5).…”

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confidence: 95%

Dissolution rate enhancement of gliclazide by ordered mixing

Saharan¹,

Choudhury

2011

Acta Pharmaceutica

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Ordered mixtures consist of adhering fine particles of a hydrophobic drug to the surface of larger particles of a water soluble carrier substance (1). Carrier particles dissolve in the presence of water, whereby adherent particles of the pharmaceutical substance disperse throughout the liquid. This eliminates the inherent tendency of hydrophobic drug particles to collect into not-readily dissolvable and dispersible aggregate. Literature reveals that various water soluble excipients such as lactose, mannitol, sorbitol and sodium chloride have been extensively used in preparation of ordered mixtures (1-3).Gliclazide is 1-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl)-3-(4-methylphenyl)sulfonylurea with molecular mass of 323.41 (PubChem Database; http://pubchem. ncbi.nlm.nih.gov). Gliclazide is used for the treatment of type II non-insulin dependent The poorly water soluble antidiabetic drug gliclazide was selected to study the effect of excipients on dissolution rate enhancement. Ordered mixtures of micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium chloride were prepared by manual shaking of glass vials containing the drug and excipient(s). Different water soluble excipients, addition of surfactant and superdisintegrant, drug concentration and carrier particle size influenced the dissolution rate of the drug. Dissolution rate studies of the prepared ordered mixtures revealed an increase in drug dissolution with all water soluble excipients. The order of dissolution rate improvement for gliclazide was mannitol > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the particle size range 355-710 mm were superior in increasing the drug dissolution rate from ordered mixtures. Reducing the carrier particle size decreased the dissolution rate of the drug as well as the increase in drug concentration. Kinetic modeling of drug release data fitted best the Hixson--Crowell model, which indicates that all the ordered mixture formulations followed the cube root law fairly well.

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“…The solubility of a compound is mainly influenced by its solute-solvent interaction, its solid-state interaction [13] as well as its ionization state. From these three main factors, the solute-solvent interactions are typically described by the partition coefficient log P [14].…”

Section: What Factors Do Influence Compound Solubility?mentioning

confidence: 99%