Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

Microstructure evaluation of dermally applicable liquid crystals as a function of water content and temperature: Can electron paramagnetic resonance provide complementary data?

Insight into the microstructure of lyotropic liquid crystals (LCs) is of crucial importance for development of novel dermal delivery systems. Our aim was to evaluate the phase behaviour of dermally applicable LCs composed of isopropyl myristate/Tween 80/lecithin/water, along the dilution line, where phase transitions are predominantly driven by increased water content. Additionally, identification of LC temperature dependence is of great importance for skin application. Selected LCs were evaluated using electron paramagnetic resonance (EPR) plus conventionally used methods of polarization microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheological measurements. Depending on water content, LCs formed diverse microstructures, from (pseudo)hexagonal (LC1) and lamellar (LC2-LC7) liquid crystalline phases that possibly co-exist with rod-like micelles (LC4-LC7), to a transitional micellar phase (LC8). Furthermore, the LCs microstructure remained unaltered within the tested temperature range. EPR was shown to detect microstructural transitions of LCs and to provide complementary data to other techniques. These data thus confirm the applicability of EPR as a complementary technique for better understanding of LC microstructural transitions that are expected to contribute greatly to studies oriented towards the drug release characteristics from such systems.

Tablets and minitablets prepared from spray-dried SMEDDS containing naproxen.

The purpose of this study was to compare different solidification techniques (i.e., adsorption technique, spray-drying process, high-shear granulation, fluid-bed granulation) for preparing solid SMEDDS powders by using solid carriers identified as appropriate and to produce a single (tablets) or multiunit (minitablets) solid dosage form based on prepared solid SMEDDS loaded with naproxen in a dissolved (6% w/w) or supersaturated (18% w/w) state. Among the solidification techniques and carriers tested, the powders produced using the spray-drying process and maltodextrin (MD) as a carrier exhibited the best self-microemulsifying properties, comparable with liquid SMEDDS. Furthermore, DoE (Design of Experiments) showed that pressure at the nozzle and pump speed (regulating feed flow rate) applied during spray drying had a major and significant influence on self-microemulsifying properties (mean droplet size and PDI) of the solid SMEDDS prepared. Furthermore, it was shown that compression of solid SMEDDS into (mini) tablets influences its self-microemulsifying properties in a negative direction. This resulted in lowering the dissolution profile of naproxen from tablets and minitablets in comparison with liquid and solid SMEDDS. However, all compressed SMEDDS formulations still had considerable influence on the dissolution profile and solubility enhancement of naproxen.