Increased dissolution rates of carbamazepine – gluconolactone binary blends processed by hot melt extrusion

Abstract

Carbamazepine (CBZ) shows a poor dissolution, therefore, it is important to enhance its dissolution in GI tract to improve its bioavailability. In the present study, a new hydrophilic carrier, d-gluconolactone (GNL), was extruded with CBZ at various molar ratios to produce granules by using hot melt extrusion (HME) processing. The granular extrudates were characterised by X-ray powder diffraction, differential scanning calorimetry and hot stage microscopy to determine the solid state of CBZ. It was found that bulk CBZ (Form-III) transformed to the polymorphic Form-I during the HME processing. GNL was proved to be an efficient carrier for CBZ to enhance the dissolution rate. The increase in the dissolution rate was observed for both physical mixtures and the extrudates of CBZ-GNL. However, the extrudates showed faster dissolution rates compared to physical mixtures in an ascending order of 2:1 < 1:1 < 1.5:1 (CBZ:GNL). The increase in the dissolution rates was attributed to the transformation of CBZ III to Form-I and also to the increased drug wettability/solubilisation in the presence of the carrier.

Solid crystal suspension of Efavirenz using hot melt extrusion: Exploring the role of crystalline polyols in improving solubility and dissolution rate

“…Hence, there is strong need to overcome the issue of poor solubility of EFV in order to enhance oral bioavailability. It has been reported in literature that various polyols, superdisintegrants and polymers can be used as a carrier in HME for solubilization of poorly water-soluble drugs (Moradiya et al, 2015;).…”

Quality aspects in the development of pelletized dosage forms

“…The most preferable processing can be done at temperature above the M.P. of semi-crystalline polymers or [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] °C above the glass transition temperature Tg of amorphous polymers, but below the M. P. of the crystalline API [ 80 , 81 ].…”

“…The increase in solubility of carbamazepine was reported by using d-gluconolactone (GNL) in hot melt extrusion [ 90 ]. The solid dispersion prepared with Eudragit EPO by hot-melt extrusion (HME) in the drug: carrier ratio of 4:1 resulted in more than 85 % drug release in just 5 min [ 91 ].…”

Synthesis and release behavior of layered double hydroxides–carbamazepine composites

“…CBZ is poorly soluble in water, and many authors have increased the solubility through its complexation with D-gluconolactone 28 , polymers 29 , cyclodextrins 30 or surfactants such as sodium lauryl sulfate and Tween 80 31 . Few works studied the incorporation of CBZ in different matrices for water remediation; this includes adsorption of CBZ on silica-based porous materials 32 , on granular carbon nanotubes /alumina hybrid adsorbent 33 , and on hematite nanoparticles 34 .…”