Preparation by HME of a soluplus-based solid dispersion containing a poorly soluble drug and a disintegration adjuvant

Purpose. to explore the feasibility of HME in the preparation of a solid dispersion of itraconazole (ITZ) and Soluplus® (SLP) also containing a formulation aid intended to improve the disintegration of the solid dosage forms (capsule or tablet) prepared with the dispersion.
Previous studies had shown a remarkable enhancement of ITZ dissolution rate from powdered SLP-based extrudates, particularly when small particles (<90 µm) were considered. However, when the same particles were filled into a gelatin capsule, drug dissolution was impaired by the formation of a swollen non-disintegrating matrix as the unit came into contact with water, reasonably because of the gelling properties of SLP. In this respect, the addition of a disintegration adjuvant would be a suitable approach, and its incorporation into the dispersion by co-extrusion with the API and the carrier may represent a step forward in the continuous manufacturing of the final dosage form.
Methods. solid dispersions were extruded in a conical co-rotating twin screw miniextruder (Minilab THERMOHAAKE). The extrudates were mill-powdered, sieved and tested for dissolution (Paddle Dissolution System 2100B, Disktek, 1L HCl 0.1M, 37°C, 100 rpm). ITZ was assayed spectrophotometrically (254 nm).
Results. in order to choose the disintegration adjuvant to be co-extruded, capsules containing physical mixtures of an ITZ/SLP solid dispersion and each of 14 selected excipients in 4:1 weight ratio were prepared and tested for dissolution performance. Amongst the candidates only croscarmellose sodium (SC) and sodium bicarbonate (SB) were able to prompt the capsule disintegration and, accordingly, the API dissolution. Therefore, formulations containing SC or SB were extruded, powdered and evaluated as such and after filling into size 0 gelatin capsules. Fast solubilization of ITZ was achieved with both disintegration adjuvants and also acceptably maintained when the dispersions were filled into capsules. SC was found slightly more effective than SB in terms of disintegration ability.
Conclusions. ternary mixtures of ITZ, SLP and a disintegration adjuvant were successfully extruded. When filled into capsules, the relevant solid dispersions showed an improved drug dissolution rate.