Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances.

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process. Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained. The products exhibited fast drug release due to preserved self-microemulsifying properties and the absence of crystalline carvedilol, which was confirmed with XRD and Raman mapping. A decrease in drug content during the stability study was observed and investigated. This was at least partially attributed to the chemical degradation of the drug. Key degradation products determined by the LC-MS method were amides formed by in situ reaction of carvedilol with fatty acids present in the oily phase of SMEDDS.

Solidification of carvedilol loaded SMEDDS by swirling fluidized bed pellet coating.

Self-(micro)emulsifying drug delivery systems (S(M)EDDS) have emerged as effective vehicles for enhancing bioavailability of poorly water soluble drugs, however solidification of the systems represents a major challenge. Objective of this study was development of carvedilol loaded liquid SMEDDS and transformation into solid pellets employing fluid-bed coating technologies. Carvedilol-loaded formulation of SMEDDS was comprised of Capmul® MCM EP, castor oil, Kolliphor® RH40 and PEG 400. The obtained liquid SMEDDS mixed with fillers and polymers was layered onto MCC pellets. Coating process was conducted in the modified, swirl-flow based fluid bed coating device, which was proved superior over the conventional Wurster fluid bed, with lower agglomeration rate. Use of polymer was essential for entrapping SMEDDS in the coating layer(s). Self-microemulsifying properties as well as fast drug release as one of main SMEDDS advantages were preserved in the solid products. Addition of lactose into the coating dispersion and applying intermediate and surface film coating to the pellets enabled higher drug loading and prevented sticking of the pellets during handling and storage. Present study indicates that the (swirling) fluid-bed pellet coating technology is a promising strategy for preparation of solid SMEDDS-coated pellets with adequate drug loading capacity and enhanced release of poorly water soluble drug.

Overview of solidification techniques for self-emulsifying drug delivery systems from industrial perspective.

Self-emulsifying drug delivery systems (SEDDS) are lipid formulations that improve solubility and oral bioavailability of the incorporated drug with poor biopharmaceutical properties. As liquids they are traditionally filled into soft or hard capsules. Transformation of SEDDS into solid dosage form has been extensively investigated in the recent years because solid dosage forms improve stability, handling and patient compliance. By using different solidification techniques selfemulsifying powders, granules, pellets and tablets can be produced. Appropriate excipients, solid carriers and processing parameters must be selected for each solidification technique to enable processability and preserve the self-emulsifying ability of the system upon its transformation into the solid formulation. In the present review various industrially applicable solidification techniques and excipients used for transforming liquid SEDDS into solid dosage forms with high production yield and good perspectives for being produced in large scales are discussed.