Abstract
In this study, spray drying from aqueous solutions, using the surface-active agent sodium lauryl sulfate (SLS) as a solubilizer, was explored as a production method for co-amorphous simvastatin–lysine (SVS-LYS) at 1:1 molar mixtures, which previously have been observed to form a co-amorphous mixture upon ball milling. In addition, a spray-dried formulation of SVS without LYS was prepared. Energy-dispersive X-ray spectroscopy (EDS) revealed that SLS coated the SVS and SVS-LYS particles upon spray drying. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that in the spray-dried formulations the remaining crystallinity originated from SLS only. The best dissolution properties and a “spring and parachute” effect were found for SVS spray-dried from a 5% SLS solution without LYS. Despite the presence of at least partially crystalline SLS in the mixtures, all the studied formulations were able to significantly extend the stability of amorphous SVS compared to previous co-amorphous formulations of SVS. The best stability (at least 12 months in dry conditions) was observed when SLS was spray-dried with SVS (and LYS). In conclusion, spray drying of SVS and LYS from aqueous surfactant solutions was able to produce formulations with improved physical stability for amorphous SVS.
Highlights
40% of drug compounds currently on the market and most of the current low molecular weight drug development candidates exhibit poor aqueous solubility [1]
It should be noted that the solubilizer concentrations used (i.e., >0.5% m/V) were above the critical micelle concentrations (CMCs) of the micelle-forming surfactants [18,19,20,21], which leads to an increase of the drug solubility as a function of the surfactant concentration (Table 1)
The results indicated that in this case incorporating LYS as a co-amorphous former did not bring significant stability or dissolution advantages when compared to formulations containing only amorphous SVS
Summary
40% of drug compounds currently on the market and most of the current low molecular weight drug development candidates exhibit poor aqueous solubility [1]. Formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug [3,4]. Even these systems are often unable to guarantee the long-term stability of amorphous drugs and there are technical challenges with manufacturing and processing of solid dispersions into oral dosage forms [5,6], only a few products of this type have reached the market. Co-amorphous drug systems containing low molecular weight excipients have recently been shown to be a promising approach for stabilization of amorphous drugs and are an attractive alternative to the traditional amorphous solid dispersion approach using polymers.
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