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.

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.

Objectives: A novel two-step flow-through in vitro lipolysis model was developed for the evaluation of drug release from a self-microemulsifying drug delivery system (SMEDDS). Methods: Firstly, the SMEDDS was dispersed in an acidic medium. Subsequently, the pH was increased, and a lipolytic reaction was immediately initiated, accompanied by medium flow onset. The latter enabled increase of the initial low pH of the medium, improving the physiological relevance of the method by simulating dosage form retainment in the stomach and transfer to the duodenum, which is very important for a weakly basic active pharmaceutical ingredient (API) incorporated in an SMEDDS. Results: Conversely to the traditional pH-stat in vitro lipolysis, the developed method is not established on titration, as the reaction vessel pH is regulated by a medium flow and buffer capacity. Individual parameters, such as pancreatin activity, buffer capacity, and medium shift, were researched using traditional pH-stat in vitro lipolysis prior to their implementation in the flow-through setup. Conclusions: The concentration of the solubilized model API, carvedilol, was increased as pancreatin activity decreased and as buffer capacity increased. The ratios between release profiles obtained under different conditions utilizing the pH-stat and novel two-step flow-through in vitro lipolysis were comparable; however, the differences were more pronounced in the flow-through method.

The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug-delivery excipient for buccal films. Gel-like dispersions were created by blending either gel or powder NCC (gNCC or pNCC) with natural polymers (alginate, pectin, or chitosan) in water, with glycerol serving as a plasticiser. Ibuprofen (IBU) as an active pharmaceutical ingredient (API) was dissolved in a self-microemulsifying drug delivery system (SMEDDS) to improve its solubility prior to its addition to gel-like dispersions. Dispersions were dried, and resulting films were cut to 3 cm × 1.5 cm size, appropriate for buccal delivery. Rheological measurements revealed that shorter, thinner, and less crystalline nanocellulose fibres are more favourable for stronger gel properties. While overall, weaker gel structure prior to film casting also resulted in shorter disintegration time, this was not the case for NCC–chitosan films; here, the low solubility of chitosan in neutral media proved to be the main obstacle. Nevertheless, the prolonged disintegration of NCC–chitosan films did not impact the dissolution of IBU, as these films exhibited the fastest dissolution rate, followed by NCC–pectin and NCC–alginate. Furthermore, NCC properties significantly influenced the dissolution behaviour of the chitosan formulations, with gNCC favouring faster IBU release due to weaker gel formation prior to film casting.

The solid-state landscape of pharmaceutical compounds is often characterized by the occurrence of polymorphs, hydrates, and solvates, which may significantly influence their physicochemical and biopharmaceutical properties. In contrast, some active pharmaceutical ingredients exhibit a remarkable resistance to crystal form diversification, despite extensive experimental investigation. In the present work, vinpocetine was subjected to an extensive solid-form screening campaign aimed at exploring its propensity to generate alternative polymorphs, hydrates, and solvates. Mechanochemical experiments were performed under neat grinding and liquid-assisted grinding conditions using a broad range of organic solvents and water, including two-step milling procedures and formulations containing surfactants. Additional investigations included high-energy planetary milling, high-pressure compaction, exposure to controlled humidity, thermal cycling, slurry-bridging experiments in various media, and crystallization after mechanochemical neutralization of vinpocetine salts. The resulting solids were systematically characterized by powder X-ray diffraction, and thermal and morphological analyses. In all cases, the recovered solid corresponded to the commercially available crystalline form of vinpocetine, with no evidence of alternative polymorphs, solvates, or hydrates. These results demonstrate the unusual robustness of vinpocetine crystal structure across a wide range of mechanical, thermal, and solvent-mediated conditions. Notably, this behavior contrasts with the well-established ability of vinpocetine to form numerous salts and salt cocrystals, suggesting that solid-state diversification in this compound is primarily driven by proton-transfer processes rather than by neutral polymorphism or solvent incorporation. The present study provides experimentally defined boundaries for the solid-state landscape of vinpocetine and contributes valuable data for future crystal-form prediction and pharmaceutical development studies. Beyond the specific findings reported herein, the systematic documentation of both successful and unsuccessful experimental outcomes represents a valuable source of experimentally validated positive and negative data that may support the future development and validation of AI-assisted crystal-form prediction tools.