James R. Falconer

Solvent Supercritical Fluid Technologies to Extract Bioactive Compounds from Natural Sources: A Review

Supercritical fluid technologies offer a propitious method for drug discovery from natural sources. Such methods require relatively short processing times, produce extracts with little or no organic co-solvent, and are able to extract bioactive molecules whilst minimising degradation. Supercritical fluid extraction (SFE) provides a range of benefits, as well as offering routes to overcome some of the limitations that exist with the conventional methods of extraction. Unfortunately, SFE-based methods are not without their own shortcomings; two major ones being: (1) the high establishment cost; and (2) the selective solvent nature of CO2, i.e., that CO2 only dissolves small non-polar molecules, although this can be viewed as a positive outcome provided bioactive molecules are extracted during solvent-based SFE. This review provides an update of SFE methods for natural products and outlines the main operating parameters for extract recovery. Selected processing considerations are presented regarding supercritical fluids and the development and application of ultrasonic-assisted SFE methods, as well as providing some of the key aspects of SFE scalability.

Preparation and characterization of progesterone dispersions using supercritical carbon dioxide

Abstract Context: Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable. Objective: To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO2. Materials and methods: The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50:50), Gelucire 44/14 and D-α-tocopheryl PEG 1000 succinate (TPGS). Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM). The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC). Results: Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO2 compared to that of untreated PGN. XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient. All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value < 0.05). Conclusion: The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.

Evaluation of progesterone permeability from supercritical fluid processed dispersion systems

Abstract The aim of this study was to investigate the permeability of unique dispersion systems prepared by supercritical fluid (SCF) processing, to deliver bioidentical progesterone (PGN) across mouse skin. Semisolid dispersions of PGN were made up of either polyethylene glycol (PEG) 400/4000, Gelucire 44/14, d-α-tocopheryl PEG 1000 succinate (TPGS), tanscutol P or myritol 318. SCF dispersion systems were compared with various control formulations; a market cream, aqueous suspension, and three conventionally prepared dispersions comelted, cosolvent and physically mixed systems. The permeability coefficient in the absence or presence of a permeation enhancer was evaluated using ex vivo mouse skin. The permeation study results for the TPGS/myritol/transcutol P dispersion system prepared using supercritical carbon dioxide (SC-CO2) had a two-fold improvement in transdermal permeation over 24 h compared to the control formulation, 245.7 and 126 µg cm−2, respectively (p value < 0.05). In this study, the skin integrity and morphology was also investigated for changes due to the formulation constituents using histological examination and Fourier transform infrared spectroscopy. The particles from the gas-saturated suspension method and SC-CO2 together with TPGS/myritol/transcutol P may offer potential advantages over the available cream on the market based on the vastly improved lag time and flux of PGN across the skin.

Extemporaneously compounded medicines

Extemporaneously compounded medicines may be useful when a required dose or dose form is unavailable commercially, or for individualised dosing.

Supercritical Fluid Technologies to Fabricate Proliposomes

Proliposomes are stable drug carrier systems designed to form liposomes upon addition of an aqueous phase. In this review, current trends in the use of supercritical fluid (SCF) technologies to prepare proliposomes are discussed. SCF methods are used in pharmaceutical research and industry to address limitations associated with conventional methods of pro/liposome fabrication. The SCF solvent methods of proliposome preparation are eco-friendly (known as green technology) and, along with the SCF anti-solvent methods, could be advantageous over conventional methods; enabling better design of particle morphology (size and shape). The major hurdles of SCF methods include poor scalability to industrial manufacturing which may result in variable particle characteristics. In the case of SCF anti-solvent methods, another hurdle is the reliance on organic solvents. However, the amount of solvent required is typically less than that used by the conventional methods. Another hurdle is that most of the SCF methods used have complicated manufacturing processes, although once the setup has been completed, SCF technologies offer a single-step process in the preparation of proliposomes compared to the multiple steps required by many other methods. Furthermore, there is limited research into how proliposomes will be converted into liposomes for the end-user, and how such a product can be prepared reproducibly in terms of vesicle size and drug loading. These hurdles must be overcome and with more research, SCF methods, especially where the SCF acts as a solvent, have the potential to offer a strong alternative to the conventional methods to prepare proliposomes.

Effects of supercritical carbon dioxide processing on optical crystallinity and in vitro release of progesterone and Gelucire 44/14 solid and semi-solid dispersions

The aim of this study was to determine the effect of supercritical carbon dioxide (SC-CO2) on the crystallinity and drug release of Gelucire 44/14-based endogenous progesterone (PGN) dispersion systems. The light scattering from PGN crystals incorporated in Gelucire 44/14 was imaged using optical microscopy. In vitro dissolution was used to determine the release kinetics of PGN, Gelucire 44/14, incorporated by a supercritical fluid (SCF) method. Release profiles were evaluated according to zero-order, first-order, Higuchi, Krosmeyer-Peppas, and dual first-order models. The dual first-order release model illustrated two distinct release rates: an initial rapid release followed by a slow diffusion of PGN from the dispersion systems. The dual first-order release model adds a new tool to the elucidation of release mechanisms from lipid and micelle-forming-based dispersion systems, where parallel processes contribute to drug release.