Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

The objective of this study was to investigate the physicochemical properties, drug release and in situ depot-forming behavior of alginate hydrogel containing poorly water-soluble aripiprazole (ARP) for achieving free-flowing injectability, clinically accessible gelation time and sustained drug release. The balanced ratio of pyridoxal phosphate (PLP) and glucono-delta-lactone (GDL) was crucial to modulate gelation time of the alginate solution in the presence of calcium carbonate. Our results demonstrated that the sol state alginate hydrogel before gelation was free-flowing, stable and readily injectable using a small 23 G needle. In addition, the ratio (w/w) of PLP and GDL altered the gelation time, which was longer as the PLP content increased but shorter as the GDL content increased. The alginate hydrogel with a ratio of PLP to GDL of 15:9 had the optimal physicochemical properties in terms of a clinically acceptable gelation time (9.1 min), in situ-depot formation with muscle-mimicking stiffness (3.55 kPa) and sustained release over a two-week period. The alginate hydrogel, which is tunable by varying the ratio of PLP and GDL, could provide a controllable pharmaceutical preparation to meet the need for long-acting performance of antipsychotic drugs like ARP.

Regulating the release of drugs precisely is one of the most important aspects of oral drug delivery systems (ODDSs). There are many formulations and preparation techniques for solving this problem, the most widely used is the application of hydrophilic polymers. Due to its high swelling rate, semi crystallinity and wide molecular weight (MW) range, Polyethylene Oxide (PEO) stands out among hydrophilic polymers. PEO is derived from the ring opening polymerization reaction of epoxyethane. When regulating oral drug release, the strength of the gel layer formed when it meets water can be adjusted by replacing different MW PEO, changing the concentration of PEO and other methods, thus affecting the release of the active pharmaceutical ingredients (APIs) in the tablet. However, with the development of its applications, it has also been found that PEO has certain limitations in regulating drug release, such as its mucosal adhesion is insufficient, low molecular weight PEO (LMW-PEO) may experience burst release, the improper use of high molecular weight PEO (HMW-PEO) may result in excessive hardness of tablets prepared therefrom, leading to delayed disintegration upon contact with the medium and consequently affecting the drug release rate. This review summarizes the factors affecting the hydrodynamics of PEO gel, including its molecular weight and concentration, environment's pH, the introduction of other polymers or additives. Then, some ideas have been proposed to address these application limitations, laying the foundation for the wider application of PEO in the future.

Objectives: To address the critical limitations of current formulations that fail to simultaneously resolve indomethacin’s poor water solubility, susceptibility to gastric acid hydrolysis, and difficulty in balancing rapid onset with long-term sustained release, this study prepared solid dispersions via anti-solvent freeze-drying to improve drug dissolution, constructed oral buccoadhesive bilayer controlled-release tablets using direct powder compression, and elucidated the intrinsic relationships among polymer gel properties, swelling-erosion behavior, tablet integrity maintenance, and drug release mechanisms. Methods: Solid dispersions (SDs) were prepared by anti-solvent freeze-drying. Bilayer tablets (25 mg IND/tablet, 12.5 mg/layer) were fabricated via direct powder compression after optimizing disintegrants and polymer matrices. In vitro dissolution, surface pH, adhesion time, and adhesion strength were evaluated. Results: SDs enhanced dissolution by at least 30-fold in water and 2.4-fold at pH 6.8 within 2 h versus pure drug. Optimized bilayer tablets achieved 45% drug release at 20 min and 80% sustained release over 8 h, with surface pH of 6.8 ± 0.1, adhesion time of 8.3 ± 0.1 h, and adhesion strength of 57 ± 0.13 g. Conclusions: The physicochemical properties of polymeric excipients are critical for balancing drug release and mucoadhesion in buccal tablets. To achieve ideal controlled-release effects, in addition to focusing on the swelling and erosion characteristics of matrix-based tablets, the ability to maintain tablet integrity during dynamic dissolution must be further investigated, which is an essential factor for ensuring precisely modulated drug release. Meanwhile, when employing solid dispersions as solubilizing intermediates to prepare controlled-release formulations, the gelling properties of polymers in each formulation component should be fully considered to avoid incomplete disintegration and insufficient release at the initial dissolution stage.