Extrusion–Spheronization Manufacture of Gelucire® Matrix Beads

Abstract

Theophylline extended-release spheres were prepared by extrusion-spheronization of matrix granulations previously obtained by incorporation of the drug in melted Gelucire 50/02 or Gelucire 55/18. Hydrophobic Gelucire 50/02 behaved as an inert matrix and released theophylline very slowly compared with hydrodispersible Gelucire 55/18, which acted as a hydrophilic matrix. Extrusion-spheronization was more easily accomplished with Gelucire 50/02. The use of ethanol as a wetting fluid increased the rate of drug release noticeably with Gelucire 50/02 and less so with Gelucire 55/18. The use of castor oil, in conjunction with ethanol to slow down the solvent evaporation, improved extrusion and spheronization. Castor oil decreased the drug release rate with Gelucire 50/02 and increased it with Gelucire 55/18. These phenomena were explained by the different solubilities of theophylline, Gelucire 50/02, and Gelucire 55/18 in ethanol and castor oil. When microcrystalline cellulose (Avicel CL 611) was used in the granulation matrix, extrusion was improved. The best formulation was obtained with Gelucire 55/18 and Avicel CL 611 and was wetted by a mixture of ethanol and castor oil. Regardless of the formulation, the mechanism of theophylline release appeared to be via Fickian diffusion.

Controlled release tamsulosin hydrochloride from alginate beads with waxy materials

“…Other studies have investigated the mechanisms by which drugs are released from Gelucires bases, using models based on the Higuchi equation for diffusion-controlled release (Howard & Gould 1987;Kopcha et al 1990Kopcha et al , 1991Montousse´et al 1999). Generally, these models are appropriate for Gelucires with a low HLB (< 7), although drug release from bases with high HLB values is thought to involve both diffusion and erosion mechanisms (Howard & Gould 1987;Kopcha et al 1990Kopcha et al , 1991.…”

Slow release drug dissolution profile prediction in pharmaceutical manufacturing: A multivariate and machine learning approach

“…A typical batch manufacturing process for time-release drugs involves granulation [8] of the raw materials, extrusion and spheronization of the resultant mix to form microspheres (referred to as spheroids or pellets) [6], drying and sieving [9], coating of the spheroids with an insoluble layer and finally encapsulation. The dissolution profile of the final product must meet target specifications with regard to the amount of drug released over time.…”

An investigation into the mechanism of dissolution rate enhancement of poorly water-soluble drugs from spray chilled gelucire 50/13 microspheres

“…For example, Gelucire 50/13 is a mixture of glycerides (mainly C16/18) and mono and diesters of PEG 1500. This material has been particularly widely studied for preparing matrix systems such as tablets and capsules as a means of achieving sustained drug release 1–5. The drug release from Gelucire 50/13 matrices has been reported to be dominated by erosion with a less pronounced diffusion component 6–8.…”