Physicochemical Investigations and Stability Studies of Amorphous Gliclazide

Abstract

Abstract. Gliclazide (GLI), a poorly water-soluble antidiabetic, was transformed into a glassy state by melt quench technique in order to improve its physicochemical properties. Chemical stability of GLI during formation of glass was assessed by monitoring thin-layer chromatography, and an existence of amorphous form was confirmed by differential scanning calorimetry and X-ray powder diffractometry. The glass transition occurred at 67.5°C. The amorphous material thus generated was examined for its in vitro dissolution performance in phosphate buffer (pH 6.8). Surprisingly, amorphous GLI did not perform well and was unable to improve the dissolution characteristics compared to pure drug over entire period of dissolution studies. These unexpected results might be due to the formation of a cohesive supercooled liquid state and structural relaxation of amorphous form toward the supercooled liquid region which indicated functional inability of amorphous GLI from stability point of view. Hence, stabilization of amorphous GLI was attempted by elevation of T g via formation of solid dispersion systems involving comprehensive antiplasticizing as well as surface adsorption mechanisms. The binary and ternary amorphous dispersions prepared with polyvinylpyrrolidone K30 (as antiplasticizer for elevation of T g ) and Aerosil 200® and/or Sylysia® 350 (as adsorbent) in the ratio of 1:1:1 (w/w) using kneading and spraydrying techniques demonstrated significant enhancement in rate and extent of dissolution of drug initially. During accelerated stability studies, ternary systems showed no significant reduction in drug dissolution performance over a period of 3 months indicating excellent stabilization of amorphous GLI.

Screening of Sacrificial Excipients for Arresting Devitrification of Itraconazole from Solid Dispersion

“…The improved stability of amorphous ITR in presence of sacrificial excipient could be explained on the basis of combination of several effects: (a) elevation of T g ; (b) hydrogen bonding between the drug and the polymer; (c) antiplasticizing effect of the polymers. 15 Therefore, it can be concluded that the sacrificial excipients could be useful to prevent devitrification process of an amorphous drug by decreasing the plasticizing effect of adsorbed water.…”

The Flow-Through Cell as an In Vitro Dissolution Discriminative Tool for Evaluation of Gliclazide Solid Dispersions

“…It also shows slow dissolution rate due to its hydrophobicity and poor wettability (Jondhale et al, 2012;Grbic et al, 2011;Biswal et al, 2008). Therefore, GLZ exhibits slow gastrointestinal absorption rate and high inter-subject variation for its bioavailability (Biswal et al, 2008;Jondhale et al, 2012;Biswal et al, 2009a;Palmerand Brogden, 1993).…”

Physical stabilization of amorphous itraconazole in solid dispersions for improved dissolution profile

“…However, key limitations associated with the amorphous phase need to be addressed are poor thermodynamic stability and higher chemical reactivity which may be attributed to stress favored devitrification during manufacturing operations and/or storage (Pokharkar et al, 2006). Further, water vapor, a plasticizer, plays an important role in adversely affecting physico-chemical properties of amorphous solids (Jondhale et al, 2012). Thus, to fully exploit solubility advantages of amorphous drugs, there is a definite need to stabilize them in solid state.…”