Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

Uttom Nandi,Dennis Douroumis,Preksha Patel,Adejumoke Lara Ajiboye,Vivek Trivedi

doi:10.3390/ph14090846

Uttom Nandi, Dennis Douroumis + Show 3 more

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https://doi.org/10.3390/ph14090846

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Abstract

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer’s glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug–polymer ratio on the successful preparation of SDs. The SIM–SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug–polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM–SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM–SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Highlights

One of the major issues limiting the biological application of a number of active pharmaceutical ingredients (APIs) is undoubtedly linked to their low aqueous solubility
The drug dissolution from physical mixtures (PMs) increased steadily with time and resulted in almost 90% SIM release after 45 min compared to 41% of the drug alone
A solvent-free scCO2 -based method was employed for the development of amorphous solid dispersions to improve the dissolution rate of simvastatin

Summary

Introduction

One of the major issues limiting the biological application of a number of active pharmaceutical ingredients (APIs) is undoubtedly linked to their low aqueous solubility. It is estimated that as many as 70% of APIs and new clinical entities have poor water solubility, which leads to a slow absorption, and an inadequate and variable bioavailability of the drug [1,2]. Approaches to improve the dissolution properties of poorly aqueous-soluble drugs include: particle size reduction, salt formation, cocrystallisation and the use of surfactants and co-solvents [3]. Each of these techniques still has their own practical limitations; for example, the difficulty in salt formation for neutral and weakly acidic/basic drugs, while the use of surfactants/co-solvents results in liquid formulations that are known to have reduced commercial viability and patient tolerability. There is an imminent need to develop alternative solubility enhancement techniques such as the development of solvent-free preparation of SDs to help overcome the aforementioned limitations

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