This study investigated the interfacial behaviors of non-ionic surfactants at the air-liquid and solid-liquid interfaces including the work of adhesion derived from surface tension and contact angle measurements and explored their potential link to the physical stability of pharmaceutical suspensions. Surface tension measurements using pendant drop tensiometry revealed varying capacities of seven non-ionic surfactants to reduce the surface tension of water, with polysorbate 20 achieving the lowest equilibrium surface tension (36.07 ± 1.08 mN/m) and poloxamer 188 the highest (48.89 ± 0.20 mN/m). Contact angle measurements were performed between 0.5 mM, 1 mM, and 2 mM surfactant solutions and thin spin-coated drug films of eight model compounds to assess solid-liquid wettability and calculate the work of adhesion. All surfactant solutions exhibited contact angles below 90°, suggesting favorable spreading on drug compound surfaces, though compound-specific differences in wettability were observed. Some surfactant-drug compound combinations, such as polysorbate 20 with naproxen or TBAJ-876, showed contact angles near 0°, potentially indicating superspreading behavior. The work of adhesion, derived from surface tension and contact angles, generally decreased in the presence of surfactants compared to water, and slightly increased with higher surfactant concentration. Pharmaceutical suspensions with the eight model drug compounds were evaluated for physical stability, assessed by monitoring the particle size profiles for 28 days at 40 °C to assess stabilization efficiency to maintain the sizes of drug particles during storage. While some correlations between low work of adhesion and poor stabilizer performance were noted - such as vitamin E TPGS with bedaquiline and poloxamer 188 with haloperidol - no consistent trend was observed across all surfactants and drug compounds. Most data clustered closely, with outliers offering limited predictive value between interfacial measurements and particle size profiles. These findings therefore suggested that although interfacial energy measurements provided valuable insight into surfactant behavior and solid-liquid interactions, they were not sufficient as standalone predictors of physical stability in pharmaceutical suspensions.

This study investigated the potential of developing long-acting injectable (LAI) formulations of the next-generation diarylquinoline antibacterial compounds TBAJ-587 and TBAJ-876, which have the potential to impact the tuberculosis (TB) treatment by providing an extended treatment option. The performance of these compounds, formulated as LAIs, were evaluated based on particle size stability, drug loading capacity, and in vivo pharmacokinetics in rats. The data showed that particularly high drug loadings could be obtained in aqueous suspensions using the salt forms of TBAJ-587 and TBAJ-876, with concentrations up to 750 mg/mL TBAJ-587 fumarate and 650 mg/mL TBAJ-876 tartrate, expressed as the equivalent concentration of free base. A long-term stability study of the TBAJ-876 tartrate formulation suggested that a relatively stable suspension was defined when stored at both ambient temperature and at 40 °C. In contrast, the TBAJ-587 fumarate suspension formulation showed significant particle size growth as a function of time, indicating physical instability in the colloidal system. Analysis of both compounds by X-ray powder diffraction (XRPD) revealed no major changes in the crystal structure following milling or after 24 weeks of storage at 40 °C. The in vivo pharmacokinetic study in rats showed that the suspensions containing either TBAJ-587 fumarate or TBAJ-876 tartrate offered a promising LAI option for the prolonged treatment of TB, as all formulations achieved prolonged drug plasma exposure for at least three months following administration.

Lipid-based-formulations (LBFs) are widely used to improve oral bioavailability of poorly water-soluble drugs. Despite their widespread use in predicting formulation performance, standard in vitro lipolysis assays often lack an absorptive sink and fail to capture the transition from gastric to intestinal environments, thereby reducing their predictive relevance for in vivo outcomes. The aim of this study was to develop a biphasic in vitro lipolysis model incorporating an absorptive sink. This might offer the potential to increase the predictive power of in vitro digestion models in the future. In this model, the absorptive sink was provided by a decanol layer, and to simulate gastrointestinal transit, two dynamic pH-transition approaches were employed: a biphasic GI-transfer model and a biphasic pH-shift model. Using nilotinib-loaded LBFs, the study established conditions for this biphasic system and examined how media composition and lipase source influence drug concentrations during formulation dispersion, digestion, and partitioning into the organic sink. The results showed that digestion experiments conducted with either porcine pancreatin or Palatase® 20000 L increased the concentration of nilotinib in the aqueous digestion medium, which correspondingly reduced partitioning of the drug into the decanol layer. For the readily dispersible Type III LBF in the biphasic GI-transfer setup, nilotinib permeation into the decanol layer decreased compared with a lipid-free control, likely due to improved drug solubilization in the aqueous digestion phase. In contrast, the poorly dispersible Type I LBF was better suited to the biphasic pH-shift setup, but it showed higher drug levels in the decanol layer, reflecting rapid partitioning of lipids-and associated crystalline drug-into the organic phase. Overall, this study establishes suitable conditions for evaluating the lipolysis of LBFs during a dynamic pH transition in the presence of an absorptive sink. This advanced approach provides additional insight to explore digestion-mediated and/or pH-mediated supersaturation during digestion of LBFs.

Levonorgestrel (LNG) is a second-generation synthetic progestogen that has been widely used in oral tablets for emergency contraception, intrauterine devices and transdermal implants. The main objectives of the present work were to evaluate LNG drug substance variability with respect to polymorphism and purity, and to investigate the stability of the compound in the selected organic solvents, pharmaceutical vehicles and biorelevant media. Solid-state analysis of LNG samples from eleven different suppliers were conducted by different analytical techniques, including Fourier transform infrared (FTIR), Raman, solid-state and liquid-state nuclear magnetic resonance (NMR) spectroscopies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (XRPD), wide-angle X-ray scattering (WAXS), small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM). In addition, dynamic vapour sorption (DVS) was performed to investigate the hygroscopicity of LNG. The comprehensive solid-state investigation of LNG from different sources showed only minor variations related to their thermal properties. Overall, all suppliers delivered the same polymorphic form of LNG and the compound displayed high physical stability under elevated temperatures and across relevant organic solvents, suggesting limited risks associated with polymorphic changes during processing. Moreover, the equilibrium solubility was obtained in a wide range of relevant organic solvents, dissolution media and pharmaceutical vehicles, which would support development of new dosage forms containing LNG.

Medication adherence plays a pivotal role in guiding the development of long‑acting injectable (LAI) formulations, including those formulated with antipsychotic compounds. Poly(lactic‑co‑glycolic acid) (PLGA)‑based microsphere formulations are available as commercial LAI products, such as Risperdal® Consta®, and are designed to improve medication adherence. Differences in monomer ratio and molecular weight across PLGA polymers allow tuning of release profiles from roughly two weeks to extended durations lasting months or years. Microsphere technologies must balance drug‑loading capacity with injectability, and this trade‑off often limits the maximum deliverable dose of therapeutic compounds. Therefore, the present work investigated the potential impact of recombinant human posterior head protein 20 (rHuPH20) when co‑administered with two PLGA‑based microsphere formulations in vivo in Sprague–Dawley rats, using risperidone as the model compound. The results indicated that co-administering rHuPH20 had limited impact on the pharmacokinetic profiles of the two PLGA-based microsphere formulations, supporting the feasibility of combining these technologies to extend the dose range for LAI microspheres. In addition, the study investigated the potential influence of injection‑site composition on risperidone release. This was assessed using the advanced Subcutaneous Injection Site Simulator (SCISSOR) in vitro dissolution model, which replicates key physiological features of the subcutaneous environment. Experiments in this system showed that albumin and collagen influenced drug‑release behavior from the PLGA-based microsphere formulations. These findings help clarify the discrepancies frequently observed between conventional phosphate‑based dissolution experiments and in vivo outcomes.

In the treatment of e.g. infectious diseases, administration of multiple drugs over extended periods is common. Long-acting injectables are used to improve patient compliance. However, formulating a single suspension containing multiple drug compounds may further improve patient compliance. This study therefore investigates the physical stability of two compounds in co-suspension focusing on stabiliser selection, stabiliser concentration, and their influence on milling efficiency and stability in both single-drug suspensions and co-suspensions prepared by wet bead milling investigating three model compounds as the dispersed phase. In total, nine stabilisers were screened in combination with itraconazole and carbamazepine in individual systems and in co-suspension of which three were selected for further evaluation with cinnarizine and itraconazole in combination, and for stabiliser concentration screening of itraconazole and carbamazepine. Physical stability was assessed by laser diffraction over 28 days of storage at 40 °C. Poloxamer 338 effectively reduced particle size while maintaining good stability in itraconazole and in co-suspensions, whereas PVP K30 was most effective for carbamazepine despite challenges with foaming. The milling behaviour of co-suspensions containing itraconazole and carbamazepine more closely resembled that of itraconazole single-drug formulations, whereas no clear stabilisation trend was observed for cinnarizine in combination with itraconazole. The stability of co-suspensions did not directly reflect that of either individual system. The optimal concentration for particle size reduction did not consistently correspond to the optimal concentration for stability, where slightly higher concentrations provided optimal stability. Increased stabiliser concentrations negatively impacted milling efficiency in carbamazepine suspensions, whereas the opposite tendency was observed for itraconazole in some systems and similarly in co-suspensions. Interestingly, co-suspensions stabilised with 0.50% (w/v) polysorbate 80 and several concentrations of poloxamer 338 produced smaller particles than the corresponding single-drug suspensions suggesting a synergistic effect when in combination.

Background/Objectives. This research supports the development of long-acting injectables (LAIs) via in situ gel (ISG) technology by illustrating the influence of drug properties and formulation variables on in vitro drug release (Part 1), and providing an example of a point-to-point in vitro-in vivo correlation (IVIVC) for celecoxib ISGs (Part 2). Methods/Results. Part 1 evaluated the in vitro release (IVR) for ISGs containing 10 mg/g of five model drugs-paracetamol, theophylline, felbinac, indomethacin, and celecoxib-using two different poly(D,L-lactide-co-glycolide) (PLGA) grades with lactide/glycolide ratios (L/G) of 50:50 or 85:15 in N-methyl-2-pyrrolidone (NMP) at polymer/solvent ratios of 30/70% or 40/60% (w/w). The results demonstrated sustained IVR, with approximately 80% of the drug released within 1 to 5 days for the sparingly soluble compounds paracetamol and theophylline ISGs, and within 1.5 to 11 days, 3 to over 20 days, and 19 to 74 days for the slightly soluble compounds felbinac, indomethacin, and celecoxib, respectively. The IVR rate increased with decreasing polymer lipophilicity and concentration and with increasing drug solubility in the IVR medium. In Part 2, the pharmacokinetics of celecoxib ISGs were assessed following subcutaneous (SC) injection in rats. A point-to-point IVIVC was established between the fraction of drug absorbed derived via deconvolution (deconvoluted Fabs) and the fraction dissolved (observed Fdiss) obtained in Part 1, based on Korsmeyer-Peppas fitting and release phase-specific scaling. Conclusions. In summary, this research highlights the significant impact of drug solubility, polymer grade, and concentration on the IVR rates of ISGs and provides an example of a point-to-point IVIVC for celecoxib ISGs with varying polymer concentrations and grades, following SC injection in rats.

During wet bead media milling, adjusting different process parameters can be key for defining the final formulation characteristics such as the particle size profiles of nano- and microsuspensions. Yttrium-stabilized zirconium (YSZ) and cross-linked polystyrene (CPS) beads are the most commonly used milling media for pharmaceutical applications which vary in bead characteristics (i.e., differences in bulk density). In the current work, it was investigated if combing these two bead types could make a more effective milling process due to the higher grinding area generated when a soft and a hard bead interact. Milling using only CPS beads led to a lower degree of particle size reduction compared to YSZ beads accompanied by a lower rise in sample temperature as the impact between CPS beads during milling was less intense than YSZ beads. The smallest sizes of drug particles were achieved using 0.2 mm YSZ beads while comparable particle size profiles were obtained using bead mixtures containing both YSZ and CPS beads. Overall, however, bead mixtures did not result in an increased size reduction of different model compounds that were investigated with different brittleness. Powder X-ray diffraction (XRPD) and Raman spectra confirmed no apparent changes in the solid-state of any of the prepared suspensions, yet indomethacin suspensions differed visually in color depending on bead type used indicating induction of amorphization below the level of quantification by XRPD and Raman. The physical stability assessment of cinnarizine suspensions milled with the different bead types, sizes, and bead mixtures showed consistent particle growth for all suspensions prepared and no distinct correlations to the bead mixtures used during mulling.

Thermodynamic solubility is a crucial parameter in drug development, yet traditional determination via the saturation shake-flask method (SSF) is often time-consuming due to the lengthy equilibration times. This study investigated the application of Adaptive Focused Acoustics (AFA), a focused ultrasonication technology, to accelerate the dissolution equilibrium of two hydrophobic drugs, atovaquone (ATQ) and praziquantel (PZQ), in polar aprotic solvents i.e., dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP). Traditional SSF required between 48 and 72 h to achieve equilibrium. However, by incorporating a 10 min AFA pre-treatment, the time required to attain thermodynamic equilibrium was significantly reduced to 2 h for PZQ in both solvents and 30 min for ATQ in DMSO. No statistically significant difference was found between the solubilities of ATQ in NMP determined using the classical SSF and the adapted SSF with the AFA pre-treatment. Powder X-ray diffraction (XRPD) was used to determine if the selected solvents triggered solid-state transformations. While PZQ (Form A) and ATQ (Form III) remained stable in DMSO, XRPD analysis revealed a complete solvent-mediated solid-state transformation of ATQ in the presence of NMP. These results demonstrate that focused ultrasonication may efficiently accelerate dissolution and reduce equilibration workflows from days to hours. However, potential for solvent-induced polymorphic or solvate transformations must be carefully monitored during the solubility assessment.

Microfluidics offers a reproducible approach to liposome manufacture; however, the impact of solvent choice on formulation performance remains underexplored. Here, we investigated whether solvent selection during microfluidic manufacturing influences liposome performance by assessing its effect on the drug release and biodistribution of liposomal doxorubicin, using rotary evaporation as a conventional method of comparison. PEGylated liposomes (DSPC:Chol:DSPE-PEG2000, 3:1:1 w/w) were prepared using a staggered herringbone microfluidic mixer, with lipids dissolved in either ethanol or Transcutol, and compared with liposomes produced by rotary evaporation and extrusion. All formulations were actively loaded with doxorubicin via an ammonium sulphate gradient, purified by tangential flow filtration, and characterised for size, polydispersity, and drug loading. The three formulations (two microfluidic (ethanol vs Transcutol) and one rotary evaporation control) were intravenously administered to Sprague–Dawley rats (1 mg/kg), and doxorubicin concentrations in plasma and tissues were quantified using LC–MS. Although solvent choice produced liposomes with broadly comparable physicochemical properties ( 100–120 nm, PDI < 0.25, encapsulation > 90

Long-acting injectable suspensions have gained increased interest for use in global health applications, however, challenges persist with complications in 'living formulations' where changes to the solidstate (crystalline or amorphous solid...

Efficient topical ocular drug delivery is critical for managing eye diseases, yet non-invasive approaches often suffer from limited retention time and low bioavailability. This study evaluated the retention time and spatial distribution of I-Drop MGD artificial tear, using Anterior segment Optical Coherence Tomography (ASOCT). Twelve healthy volunteers were enrolled, each assessed in both eyes across four visits, yielding a dense, paired dataset with high statistical power and reduced inter-subject variability. Baseline assessments showed a strong correlation between the central corneal thickness (CCT) measurements in fellow eyes and minimal variability across visits. Following instillation, CCT increased sharply and then decayed over time, consistent with tear film clearance. Retention time, estimated by exponential fitting, had a mean of 13. 94 ± 16.32 minutes and a median of 7.7 minutes (3.4-16.78 minutes). Qualitative image analysis revealed that thinner, well-distributed films cleared more slowly than thicker accumulations, suggesting that film morphology influenced drainage dynamics. Although the administration volume was fixed, differences in ocular surface area, due to natural variation in anatomy, appeared to affect the distribution of the formulation and, consequently, retention behavior. Statistical analyses further demonstrated that neither blinking rate nor tear film break-up time (TBUT), within physiological ranges, significantly impacted retention time for healthy subjects. Similarly, subjective discomfort levels reported after installation had no measurable effect. Statistical power analysis confirmed that the paired-eye, multi-visit design was robust, requiring as few as four subjects to detect treatment effects with approximately 81 % power based upon the tested eye drops. Overall, the findings supported the use of ASOCT for high-resolution, non-invasive assessment of ocular formulation retention and suggested that future design of ophthalmic vehicles should account for film-distribution behavior and rheological properties to optimize performance.

Long-acting injectables improve treatment outcomes for chronic diseases by reducing dosing frequency. Long-acting injectables may be formulated as nano- or microsuspensions produced by wet bead milling and homogenization often facing physical instability. This study investigates different stabilizers' ability to prevent particle growth, caking and the influence on resuspendability. Eight different stabilizers; polysorbate 20 (PS20), polysorbate 80 (PS80), poloxamer 188 (P188), poloxamer 338 (P338), polyvinylpyrrolidone K17 (PVP K17), polyvinylpyrrolidone K30 (PVP K30), vitamin E-TPGS, and sodium lauryl sulphate (SLS) and one potential resuspending agent (polyethylene glycol 4000) was used to assess the stability and resuspendability of indomethacin suspensions. The stability and resuspendability was assessed during four weeks of storage at three different temperatures for all stabilizers at five different concentrations. PVP K30, PVP K17 and P338 yielded stable indomethacin suspensions with minor particle growth. Statistical and machine learning modelling identified stabilizer type as a critical factor influencing resuspendability. Increased storage temperature was found to negatively impact resuspendability, particularly in formulations containing polysorbates. Addition of the resuspending agent PEG4000 did not have significant impact on the resuspendability of vitamin E-TPGS and PS20 formulations while it had a negative effect on the resuspendability of formulations with PVP K30 and P338.

Many active pharmaceutical ingredients suffer from poor water solubility, short plasma half-life, low permeability, or limited chemical stability in aqueous solutions, posing significant challenges for drug formulation. Cyclodextrins (CDs) can form inclusion complexes with various drugs, enhancing both their solubility and chemical stability in aqueous environments. In pharmaceutical formulations, pH control is crucial, and buffers are commonly used to maintain solution stability. However, previous studies suggest that certain buffers can interact with CDs, leading to competitive binding that may affect drug complexation. This study examines the effects of twelve pharmaceutically relevant buffers on the inclusion complex between α-cyclodextrin (α-CD) and 1,9-nonanediol using isothermal titration calorimetry to determine complexation constants and thermodynamic parameters. The results indicate that the complexation constant is buffer species-specific. Four carboxylic acid-based buffers-fumaric acid, succinic acid, maleic acid, and malic acid-demonstrated competitive interactions with α-CD, significantly reducing its ability to complex 1,9-nonanediol. In contrast, phosphate, MES, Tris, and tartaric acid showed minimal interaction. Additionally, the data suggests that increased polarity from additional hydroxyl groups in carboxylic acids decreases their competitive binding affinity. Complexation with hydroxypropylated α-cyclodextrin (HP-α-CD) consistently showed lower binding constants, attributed to steric hindrance and increased cavity hydrophilicity. These findings highlight the importance of buffer selection in cyclodextrin-based drug formulations and suggest that buffer-CD interactions are dependent on both buffer structure and CD cavity size.

For release testing of lipid-based formulations (LBFs), lipid digestion using the pH-stat approach is widely used despite the fact that it is a laborious exercise and predictivity towards in vivo performance could not be demonstrated. A probable reason is the lack of differentiation between readily absorbable (molecularly dissolved) and less absorbable (colloid associated) drug fractions. This work describes the development and testing of an alternative approach designed to address both issues of the pH-stat method, the labor-intensive nature and the limited ability to estimate in vivo behavior. The proposed solution involves combined lipolysis-permeation testing on 96-well microtiter sandwich plates. In this new time-efficient and material-sparing approach, a highly buffered lipolysis medium was used in the donor chamber to avoid the need for pH stabilization by titration. Moreover, the method was optimized to minimize non-specific adsorption of cinnarizine to the plates and polytetrafluoroethylene (PTFE)-coated stirring bars. The predictive power of the new high throughput screening (HTS) to estimate in vivo oral bioavailability of cinnarizine-loaded type I LBFs was evaluated against recent oral bioavailability data of the very same formulations in rats and compared to in vitro data generated by the pH-stat lipolysis approach. The following variables were studied: supersaturation, lipase inhibition, lipid chain length, and presence of an amphiphilic polymer (precipitation inhibitor). While the HTS method correctly captured the in vivo impact of both supersaturation and lipase inhibition for all formulations, the pH-stat method revealed opposite trends for one out of four combinations in each formulation sets. In vivo there had been no effect observed for lipid chain length nor presence of the amphiphilic polymer. In contrast, both in vitro approaches wrongly predicted such effects in some cases. A better prediction for the long-chain systems was found with the HTS method as with the laborious pH-stat approach. The HTS lipolysis-permeation method can test multiple formulations in the 96-well plate format within hours and gave IVIVCs of up to 0.91 for grouped type I LBFs. In particular the in vivo performance of supersaturated formulations was correctly captured. This study demonstrates that this new method represents a promising alternative to existing tools for prediction of the in vivo performance of type I LBFs.

Surfactants are typically used as solubility enhancers of drug compounds but also as stabilizers during the preparation of nano- and microsuspensions. In this context, their solubilizing properties may inadvertently alter the particle size over time, potentially affecting the drug release profile. Therefore, selecting appropriate stabilizers with optimal affinity to prevent particle agglomeration and stabilization concentration is crucial to ensure the physical stability and efficacy of the suspension. For that reason, the present study explored naproxen suspensions prepared with dual centrifugation while stabilized with polysorbate 20, poloxamer 188, or a combination of both to determine the importance of stabilizer/drug affinity and drug solubility in the presence of the surfactants. The thermodynamic solubility of naproxen in the presence of polysorbate 20 was almost eight times higher than in the presence of poloxamer 188. The increased solubility induced by polysorbate 20 seemed to impact the size of naproxen particles just after milling due to excess surfactant present in the suspensions, i.e., a minimum concentration of stabilizer seemed to exist just after milling where the preferable concentration should be kept above 0.75 % and below 2.00 % (w/v) to obtain the smallest size distribution. In contrast to this, indications towards improved physical stability with time was observed for suspensions which contained excess surfactant. By combining both surfactants, the sizes of naproxen particles just after milling did not increase at higher stabilization concentrations while it was also possible to use lower concentrations of poloxamer 188 to decrease the sizes of naproxen particles. Naproxen particles were generally unstable during 28 days of storage at 40 degrees C and an increase in particle size distribution was observed every week of measurement when stabilized with polysorbate 20 and poloxamer 188. Yet, improved physical stability profiles were obtained when polysorbate 20 and poloxamer 188 were combined, when compared to suspensions stabilized with the individual surfactants, indicating a stabilization synergism between the two surfactants for naproxen suspensions during the short-term evaluation. In general, the study showed that the stabilizer concentration needed to obtain a smaller particle size after milling was not sufficient and it did not lead to the most stable suspensions while the lack of solubilization capacity of the stabilizer was a poor predictor for physical stability of naproxen suspensions.

The present investigation aims to evaluate the loading of hydrophilic molecules with varying physicochemical properties in LeciPlex (R). Polysorbate 80, taurocholate, and dioctadecyldimethylammonium bromide (DODAB) were used to prepare non-ionic, anionic and cationic LeciPlex (R) respectively, and their interactions with two model hydrophilic compounds differing in molecular weight, surface charge and structural features are explored. A negatively charged peptide, daptomycin was encapsulated via passive loading, while a positively charged amphipathic base, acridine orange required a remote loading. All formulations were characterized for particle size, zeta potential, and entrapment efficiency. Daptomycin and acridine orange LeciPlex (R) were further characterized by transmission electron microscopy (TEM) and evaluated for in vitro release profiles by dialysis bag method. In addition to the above characterizations, daptomycin-loaded LeciPlex (R) was further evaluated for thermal behavior using differential scanning calorimetry (DSC), antimicrobial efficacy via the resazurin assay, haemocompatibility and physicochemical stability. The type of stabilizer and phospholipid concentration directly influenced the particle size and entrapment of daptomycin LeciPlex (R). The average particle size of daptomycin-loaded LeciPlex (R) was lower compared to the acridine orange-loaded LeciPlex (R). Acridine orange entrapment (55-80 %) increased with cholesterol incorporation. TEM revealed uni or oligo lamellar vesicles. DSC confirmed the interaction of daptomycin with lipid in all three daptomycin-LeciPlex (R) systems. Both daptomycin and acridine orange LeciPlex (R) systems demonstrated sustained release profiles and improved stability. Daptomycin LeciPlex (R) showed comparable antimicrobial efficacy to that of the solution and exhibited minimal haemolysis. Present study demonstrated the successful encapsulation of structurally diverse hydrophilic molecules into LeciPlex (R) using a simplified and scalable approach.

This study investigated the complexation behavior between different cyclodextrins (CDs) and various preservatives used in topical ocular formulations, including benzyl alcohol, phenethyl alcohol, benzalkonium chloride, and sorbic acid. The investigations were conducted using nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), and heat capacity analysis. NMR data revealed distinct chemical shift changes, indicating strong interactions between the aromatic rings of the preservatives and the CD cavities, with β-CD demonstrating the most significant shifts for benzyl alcohol and phenethyl alcohol, and α-CD exhibiting the strongest interaction with benzalkonium chloride and sorbic acid. ITC analysis confirmed varying complexation constants, with benzalkonium chloride showing the highest affinity towards CDs, particularly α-CD, while γ-CD demonstrated the weakest binding across all preservatives. Temperature dependence studies showed that the complexation constant for benzalkonium chloride and sorbic acid with α-CD decreased with increasing temperature, a trend supported by van’t Hoff analysis, which indicated a correlation between theoretical and empirical data for these systems. Heat capacity measurements revealed predominantly negative values, indicative of hydrophobic interactions driving complexation, except for benzyl alcohol complexed with α-CD, which showed a positive heat capacity due to conformational changes. Overall, this study highlighted the differential binding affinities of preservatives with CDs, with β-CD forming the most stable complexes with benzyl alcohol and phenethyl alcohol, and α-CD showing the strongest interactions with benzalkonium chloride and sorbic acid, emphasizing the impact of structural features and temperature on inclusion complex formation and thereby a physical pharmaceutical input when formulating topic ocular formulations that would need solubilization applying CDs and preservation.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30–50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) —DNA-based structures with cytotoxic proteins—that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly—without systemic absorption—could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.

The physical stability of nano- and microsuspensions is a crucial factor to consider during formulation investigation and optimization. Short-term stress studies are often used as predictive studies to evaluate the long-term physical stability of pharmaceutical suspensions. The short-term stress stability of cinnarizine suspensions prepared with dual centrifugation (1 mL scale) was therefore compared to the long-term storage stability, i.e., 18 months of cinnarizine suspensions milled with an agitator bead mill in up-scale. Storage temperature was the main factor impacting the particle size profiles of cinnarizine suspensions stabilized with polysorbate 20 in both short-term stress studies and long-term stability assessment. During short-term stress studies, only minor changes in sizes of particles were seen for suspensions subjected to mechanical stress factors such as rotation or shaking for 72 h where the increase in particle sizes was mainly attributed to the adjustment of storage temperature. Thermal cycling resulted in destabilization of cinnarizine suspensions with minor improvement of the particle size profiles with the addition of mannitol when subjected to heating and freezing. Early indications in the short-term assessment also showed that 1 % (w/v) polysorbate was sufficient for the apparent short-term physical stability when stored at different storage temperatures. Smaller sizes of cinnarizine particles were obtained with a higher concentration of polysorbate 20 during thermal cycling, similar to the improvement in the long-term stability of cinnarizine suspensions stabilized with higher stabilization concentration, indicating that higher percentage of polysorbate 20 as the stabilizer was necessary at long versus short term stability. Storage at 5.0 °C resulted in somehow physical stable suspensions with time, whereas long term storage at 25 °C and 40 °C resulted in increased particle sizes with time, especially in the case of suspensions that were stabilized with the lowest concentration of polysorbate 20 (1 % w/v), where the majority of the prepared suspensions were unmeasurable after 78 weeks of storage.