The aim of this study was to develop a four-component self-nanoemulsifying drug delivery system (FCS) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). In the solubility test, PZH showed a highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) and was solubilized at 70 °C in the order Kollisolv PG (5.38%, w/w) > Kolliphor RH40 (0.49%) > Capmul MCM C10 (0.21%) and Capmul MCM C8 (0.19%), selected as the solubilizer, the surfactant, and the oils, respectively. In the characterization of the three-component SNEDDS (TCS) containing Kolliphor RH40/Capmul MCM C10, the particle size of dispersion was very small (95% at 120 min) at four different pHs with 1% polysorbate 80, whereas the raw PZH and Kollisolv PG solution showed a pH-dependent poor dissolution rate (about 40% at 120 min), specifically at pH 6.8 with 1% polysorbate 80. In conclusion, PZH-loaded FCS in this work demonstrated enhanced solubility and a consistent dissolution rate regardless of medium pH.

Background/Objectives: The aim of this work was to prepare and characterize gastroretentive floating combination tablets (GRCTs) containing 500 mg of amoxicillin trihydrate (AMX) and 125 mg of levofloxacin (LVX) that provide sustained drug release and stability at gastric pH levels for the eradication of resistant Helicobacter pylori. Method: GRCTs were prepared with low-density excipients and hydrophilic swellable polymers, including hydroxypropyl methylcellulose (HPMC) of various viscosities, polyethylene oxide (PEO), and carboxymethylcellulose (CMC), by the direct compression method. The prepared GRCTs were investigated and optimized in terms of pH stability, tablet hardness, floating lag time and total floating time, drug release rate, gel strength. Results: AMX and LVX in GRCT were stable at the HP eradication target pH above 4.0. The effervescent GRCT composition (AMX/LVX/HPMC [4000 cP]/CMC/microcrystalline cellulose/citric acid/sodium bicarbonate/calcium silicate/silicon dioxide/magnesium stearate = 500/125/50/50/125/40/60/30/10/10, w/w) yielded acceptable hardness (>6 kp), reduced floating lag time (12 h), and sustained release rates of AMX and LVX (>90% until 12 h). This optimized GRCT had a gel strength of 107.33 ± 10.69 g and pH > 4.0, which maintained the tablets’ shape and AMX stability for 12 h. Conclusions: Collectively, the formulated effervescent GRCTs combining AMX and LVX represented a promising candidate dosage form for eradicating resistant H. pylori.

The present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosity hydroxypropyl methylcellulose (HPMC 4.5cp) was selected and worked efficiently to suppress REB precipitation at 40 °C for 16 days. The additionally optimized eye drops formulation (F18 and F19) using aminocaproic acid and D-sorbitol as a buffering agent and an osmotic agent, respectively, demonstrated long-term physicochemical stability at 25 °C and 40 °C for 6 months. The hypotonicity (<230 mOsm) for F18 and F19 noticeably extended the stable period, since the pressure causing the REB precipitation was relieved compared to the isotonic. In the rat study, the optimized REB eye drops showed significantly long-lasting pharmacokinetic results, suggesting the possibility of reducing daily administration times and increasing patient compliance (0.50- and 0.83-times lower C_max and 2.60- and 3.64-times higher exposure in the cornea and aqueous humor). In conclusion, the formulations suggested in the present study are promising candidates and offer enhanced solubility, stability, patient compliance, and bioavailability.

This study aimed to develop electrolyte complexes of paliperidone (PPD) with various particle sizes using cation-exchange resins (CERs) to enable controlled release (both immediate and sustained release). CERs of specific particle size ranges were obtained by sieving commercial products. PPD–CER complexes (PCCs) were prepared in an acidic solution of pH 1.2 and demonstrated a high binding efficiency (>99.0%). PCCs were prepared with CERs of various particle sizes (on average, 100, 150, and 400 μm) at the weight ratio of PPD to CER (1:2 and 1:4). Physicochemical characterization studies such as Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy between PCCs (1:4) and physical mixtures confirmed PCC formation. In the drug release test, PPD alone experienced a complete drug release from PCC of >85% within 60 min and 120 min in pH 1.2 and pH 6.8 buffer solutions, respectively. Alternatively, PCC (1:4) prepared with CER (150 μm) formed spherical particles and showed an almost negligible release of PPD in pH 1.2 buffer (75%, 24 h). The release rate of PPD from PCCs was reduced with the increase in CER particle size and CER ratio. The PCCs explored in this study could be a promising technology for controlling the release of PPD in a variety of methods.

The objective of this work was to develop a supersaturated gel formulation (SGF) loaded with the maximum atorvastatin calcium trihydrate (ATR) dose. The maximum dose strength of ATR needs to be reduced through improving solubility and dissolution rate to mitigate side effects due to the necessity of taking high doses. ATR has highly pH-dependent solubility at 37 °C, leading to poor solubility (60%, w/w), and the combined use of TPGS and PEG 200 formed an organogel state and suppressed ATR precipitation, showing 15-fold higher dispersion solubility in buffer solution at pH 1.2 compared to the formulation with PEG 200 alone. The optimal SGF composition (ATR/PEG 200/TPGS = 10/60/30, w/w) exhibited an over 95% dissolution rate within 2 h at pH 1.2, compared to less than 50% for the original commercial product. In a transmission electron microscope analysis, the SGF suppressed ATR precipitation and revealed smaller precipitated particles (<300 nm) compared to the control samples. In the XRD analysis, the SGF was physically stable for 100 days at room temperature without the recrystallization of ATR. In conclusion, the SGF suggested in this work would be an alternative formulation for the treatment of dyslipidemia with enhanced solubility, dissolution, and physical stability.

This study aimed to develop a supersaturated liquid formulation (SSLF) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). SSLFs were prepared by a simple stirring method in a heated silicon oil bath (70 °C). PZH showed highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) at 37 °C. The SSLF containing glycerol and polyvinylpyrrolidone K30 (PVP K30) increased PZH dispersion solubility (273.66 ± 48.91 μg/mL) at pH 6.8 by more than 50-fold compared with that of glycerol alone (<5 μg/mL), and the PZH precipitate particle size was considerably small (90%) and 6.8 (>55%) until 360 min, whereas PZH powder and PZH glycerol solution showed pH-dependent, low dissolution rates (<10%) under similar conditions. The supersaturation ratio of SSLF10 was very high at 29.88 and 18.36 at pH 6.8 and 4.0, respectively, indicating a stable PZH supersaturation solution. In the transmission electron microscopy analysis, PVP K30 and PG in SSLF10 synergistically suppressed PZH precipitation and recrystallization with small amorphous particles (<200 nm). Therefore, SSLF10 would be a promising formulation with enhanced solubility and dissolution rates regardless of medium pH.