Improvement of Dissolution Rate of Gliclazide Through Sodium Salt Formation

Abstract

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.

<p>Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study</p>

“…It is worth mentioning that gliclazide degraded after 10 hrs in the gastric pH (1.2) and showed to be highly stable at the alkaline pH values as reported by Bansal et al 34 The drug, however, stays in the stomach for only 2 h; a duration of time during which the drug proved to be stable. [35][36][37][38] Consequently, phosphate buffer pH 7.4 was chosen as dissolution medium for gliclazide as documented in BP. 39 The optimum lyophilized GLZ loaded formulation (10 F2) was compared to the raw GLZ powder, and GLZ commercial tablets (immediate release (IR)).…”

Enhancement of the Dissolution Rate of Indomethacin by Solid Dispersions in Low-substituted Hydroxypropyl Cellulose

“…The use of acidic medium (pH 1.2), and two intestinal media (pH 4.5 and pH 6.8, respectively) is proposed to evaluate the differences in the dissolution rate of various IND formulations. These media have been used by different authors to compare various drug formulations that present substantial changes in solubility during their gastro-intestinal transit [29][30][31] .…”

Gliclazide: Biopharmaceutics Characteristics to Discuss the Biowaiver of Immediate and Extended Release Tablets

“…Gliclazide has been reported as a drug practically insoluble in water [38], freely soluble in methylene chloride, sparingly soluble in acetone and slightly soluble in ethanol [39]. It presents low solubility in water at 25 • C (34-37 µg/mL) as well as at 37 • C (52-55 µg/mL) [32,38,[40][41][42][43].…”

“…Starting from pH 4.5, there is a direct relation of the increase of pH and of the solubility. This was expected, since the drug behaves like a weak acid due to its sulfonamide group (pKa 5.8) [34,35] ionizing in media with higher pH values, resulting in higher solubilities in these conditions [40,47]. Furthermore, this drug behaves like a base due to the alicyclic aliphatic amine group (pKa 2.9) which, in acid pH (1.2) protonates and acquires positive charge [40].…”