Nanocellulose-Based Film-Forming Hydrogels for Improved Outcomes in Atopic Skin.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by impaired skin barrier function. Amongst the various dermal formulations that are being used and/or investigated for AD treatment, one of the advanced approaches is the use of hydrogels as film-forming systems that are applied directly to the skin and have the added value of providing a physical barrier, which is lacking in atopic skin. Novel film-forming hydrogels based on two different nanocrystalline celluloses (NCCs) in combination with one of two natural polymers (alginate or pectin) were developed for incorporation of betamethasone dipropionate (BDP). Initially, the low water solubility of BDP was resolved by prior dissolution in a self-microemulsifying drug delivery system (SMEDDS). The mixture of Kolliphor® EL/Capryol® 90 in a ratio of 8/2 was chosen on the merit of its high BDP-saturated solubility and no BDP precipitation upon water dilution, enabling BDP to remain dissolved after incorporation into hydrogels. The solvent evaporation method was used to prepare the films, and their high water retention capacity was confirmed in vitro on artificial membranes and pig ear skin. The presented results thus confirm NCC-based film-forming hydrogels as a very promising drug delivery system for AD treatment.

High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility.

Mesoporous carriers are a convenient choice for the solidification of self-microemulsifying drug delivery systems (SMEDDS) designed to improve the solubility of poorly water-soluble drugs. They are known for high liquid load capacity and the ability to maintain characteristics of dry, free-flowing powders. Therefore, five different mesoporous carriers were used for the preparation of carvedilol-loaded SMEDDS granules by wet granulation methods-in paten (manually) and using a high-shear (HS) granulator. Granules with the highest SMEDDS content (63% and 66% of total granules mass, respectively) and suitable flow properties were obtained by Syloid® 244FP and Neusilin® US2. SMEDDS loaded granules produced by HS granulation showed superior flow characteristics compared to those obtained manually. All SMEDDS granules exhibited fast in vitro release, with 93% of carvedilol releasing from Syloid® 244FP-based granules in 5 min. Upon compaction into self-microemulsifying tablets, suitable tablet hardness and very fast disintegration time were achieved, thus producing orodispersible tablets. The compaction slightly slowed down the carvedilol release rate; nevertheless, upon 1 h (at pH 1.2) or 4 h (at pH 6.8) of in vitro dissolution testing, the amount of released drug was comparable with granules, confirming the suitability of orodispersible tablets for the production of the SMEDDS loaded single unit oral dosage form.

Self-microemulsifying tablets prepared by direct compression for improved resveratrol delivery.

The purpose of this study was to develop self-microemulsifying (SME-) tablets to improve resveratrol solubility whilst delivering resveratrol in a preferred tablet dosage form. Resveratrol was dissolved in liquid self-microemulsifying drug delivery system (SMEDDS) (10% w/w) and solidified through adsorption on several different solid carriers. Two ranges of synthetic amorphous silica (Sylysia® 290, 350, 470, 580; Syloid® 244FP, AL-1FP) as well as granulated magnesium aluminometasilicate (Neusilin® US2) were screened for their SMEDDS adsorbent capacity. The most efficient carrier from every range was chosen for further SME-tablet development. To counteract the high ratio of liquid in SME-tablets, additional dry binders (microcrystalline cellulose, copovidone) were added to the tableting mixture, as well as superdisintegrant (croscarmellose sodium) and lubricant (magnesium stearate). Finally, approx. 600 mg tablets were directly pressed using 12 mm flat face punch, containing 41.75% SMEDDS. Overall, all tablets exhibited sufficient hardness (>50 N), although it was negatively affected by higher compression force. Tablets with Neusilin® US2 proved to have highest hardness, as granulated structure of Neusilin® US2 provided best compaction properties needed for successful direct compression of tablets. All prepared SME tablet formulations disintegrated in under 10 min and formed microemulsions (droplet size < 100 nm) upon dilution with water, with Neusilin® US2 tablets exhibiting the lowest droplet size (<30 nm). While conventional dissolution test indicated incomplete resveratrol release from solid carriers in both pH 1.2 and 6.8 media, no difference fatty acid amount titrated during fasted state in vitro lipolysis between liquid and solid SMEDDS was observed. Moreover, accelerated stability tests confirmed over 90% of trans-resveratrol remained in solid SMEDDS following 90 days at 40 °C, with no crystallization of resveratrol observed during that time. To sum up, through adsorption on solid carriers, in particular Neusilin® US2, SMEDDS was successfully transformed into a directly compressible mixture and tableted without the loss of its self-microemulsifying ability.