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Physicochemical characterization of solid dispersion systems of tadalafil with poloxamer 407 Dissolution behaviour of a poorly water-soluble drug, tadalafil, from its solid dispersion systems with poloxamer 407 has been investigated. Solid dispersion systems of tadalafil were prepared with poloxamer 407 in 1:0.5, 1:1.5 and 1:2.5 ratios using the melting method. Characterization of binary systems with FTIR and XRPD studies demonstrated the presence of strong hydrogen bonding interactions, a significant decrease in crystallinity and the possibility of existence of amorphous entities of the drug. In the binary systems tested, 1:0.5 proportion of tadalafil/poloxamer 407 showed rapid dissolution of tadalafil (DE30 70.9 ± 3.6 %). In contrast, higher proportions of poloxamer 407 (1:1.5 and 1:2.5) offered no advantage towards dissolution enhancement of the drug, indicating altered rheological characteristics of the polymer at its higher concentration, which might have retarded the release rate of tadalafil.

The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA), were prepared with β-cyclodextrin (βCD) with or without addition of l-arginine (ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE) of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear) type of solubility curve in presence and absence of ARG, the CE and association constant (Ks) of βCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation.

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.

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The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with beta-cyclodextrin (betaCD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyleneglycol 6000 were investigated. The phase solubility profile of lamotrigine with betaCD was classified as AL-type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96+/-2.26 M(-1). Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine.

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