This study examined the impact of lyophilization on the anti-inflammatory, antioxidant, and antimicrobial properties of three probiotic candidates, and subsequently developed an oral delivery system to protect probiotics from the adverse conditions within intestinal tract and preserve their activity in the colon. Antioxidant capacity was assessed indirectly using a ferrous iron colorimetric assay, while anti-inflammatory potential was evaluated in HT29 cells by quantifying cytokine secretion. The antimicrobial activity of the probiotic strains was evaluated against Staphylococcus aureus and Listeria monocytogenes using different probiotic fractions. The probiotic delivery system was produced using the Buchi® encapsulator. The results revealed that the antioxidant and the anti-inflammatory capacities of the three Lactobacilli strains were preserved after lyophilization. Specifically, the strains reduced inflammation by approximately 40% and exhibited high antioxidant activity (729 ± 73 µmol/L). As expected, the extracellular fraction of the probiotics retained its ability to inhibit both pathogens after lyophilization. In addition, the developed delivery system achieved a high encapsulation rate for each strain. However, further evaluation is needed after their incorporation into multiparticulate vectors to ensure sustained activity and targeted release. Combining these three probiotic strains into a single delivery vehicle may enhance their overall biological effects in the colon.

Lipid-based formulations (LBFs) represent a promising strategy to improve the oral absorption of poorly soluble and poorly permeable compounds, such as BCS Class IV drug. Nevertheless, the development of lipid formulations requires predictive in vitro models that closely mimic in vivo physiology, allowing for more reliable estimation of oral absorption. Permeability studies using culture cells monolayers can contribute to evaluate the influence of formulation components as well as the interplay between solubilisation and permeation. In this study, the cytotoxicity of ticagrelor, a BCS class IV drug, and placebo formulations was first assessed in Caco-2 cells, and selected LBFs were subsequently validated in both Caco-2 monoculture and Caco-2/HT29-MTX co-culture. The apparent permeability (Papp) was estimated using the well-established Caco-2 monoculture model and the more innovative Caco-2/HT29-MTX co-culture, which incorporates mucus secretion to better mimic the intestinal barrier. LC/MS analysis from permeability studies revealed that the apparent permeability coefficient of the pure API (1.02 × 10-7 cm/s for monoculture and 1.25 × 10-7 cm/s for co-culture) was significantly enhanced, by a factor ranging from 4.6 to 9.4 for monoculture, and from 2.1 to 6.6 for co-culture, when formulated in LBFs. The inclusion of permeation enhancers in the LBFs increased Papp values compared for LBFs without permeation enhancers. Overall, a decrease in permeability was observed in the co-culture model due to the mucus barrier, although this reduction was not statistically significant for the majority of tested formulations.

Amorphous solid dispersions (ASDs) are widely recognized as an effective formulation strategy to enhance the in vivo performance of poorly water-soluble drugs; however, their broader application is often limited by insufficient long-term physical stability especially if the drug load is higher than the saturation concentration of the drug in the polymer under standard storage temperature conditions. In this study, the objective was to investigate the functional role of a lipid coating in modulating physical stability and in vitro release and bioaccessibility of a supersaturated praziquantel amorphous solid dispersions (ASD-PZQ). ASD-PZQ systems composed of praziquantel and a vinylpyrrolidone-vinyl acetate copolymer was coated using two lipid-based formulations predominantly composed of either beeswax or tristearin. These lipid systems differ in chemical composition, physicochemical characteristics, and biopharmaceutical behavior, particularly with respect to lipid digestibility. Selected additives (surfactants) were incorporated to tailor manufacturability, stability, and coating functionality. As amorphous systems are particularly sensitive to moisture-induced recrystallisation, the coated ASDs were deliberately directly exposed to harsh storage conditions, namely excessive humidity (60% RH) and their physical stability was monitored over a six-month period. To better capture the complexity of gastrointestinal processes, the bioperformance of the lipid coating was assessed using an in vitro multicompartmental digestion model. From a stability standpoint, the lipid coating reduced moisture-induced plasticization during storage. In terms of biopharmaceutical performance, ASD-PZQ coated with beeswax-based formulations exhibited enhanced bioaccessibility compared with uncoated ASD-PZQ, whereas tristearin-based coatings resulted in a prolonged drug release profile. Overall, this work demonstrates that a lipid coating on supersaturated amorphous solid dispersions would mitigate key stability challenges associated with ASD development but also enables the introduction of new functional attributes. These findings position lipid-coated ASDs as advanced, multifunctional drug delivery systems for poorly water-soluble compounds and reinforce their relevance as highvalue platforms in pharmaceutical research.

The potential of Adansonia digitata (baobab) pulp polysaccharides (BB), combined with whey protein (WP) and alginate (ALG), was evaluated as a novel pharmaceutical excipient to enhance the viscosity, swelling behavior, controlled release, and mucoadhesive properties of hydrogels prepared by the ionotropic gelation technique. Hydrogels based on BB, WP, and ALG, alone or in combinations (WP/BB, WP/ALG, ALG/BB, and WP/ALG/BB), were characterized by infrared spectroscopy and zeta potential measurements. Rheological, swelling, controlled release, and mucoadhesion studies were conducted to assess the functional contribution of BB and its synergistic effects with WP and ALG. All polymers exhibited viscoelastic solid behavior (G' > G″). For each polymer, with or without crosslinking, molecular interactions were observed, leading to variations in the Tan δ parameter. The crosslinked WP/ALG/BB hydrogel exhibited reduced polymer swelling and provided a more sustained release of the incorporated active substance. In vitro and ex vivo studies demonstrated strong interactions between the polymeric matrices and intestinal mucus, with the WP/ALG/BB system showing the highest mucoadhesion. Further in vivo investigations are needed to confirm the ability of BB to enhance the oral bioavailability of active substances. Overall, Adansonia digitata pulp polysaccharides, in combination with whey protein and alginate, represent a promising natural excipient for the development of bioadhesive hydrogels and cold-gelled delivery systems in pharmaceutical formulations.

Lactic acid bacteria (LAB) are widely recognized as probiotics due to their health-promoting properties. Some strains can perform both aerobic metabolism and fermentation, which may influence their biological functions. This study investigated the impact of Lactobacilli metabolism on three specific biological functions: anti-inflammatory, antioxidant, and antimicrobial effects, across eleven LAB strains. To this end, growth profiles under aerobic and anaerobic condition were monitored by turbidity. Antimicrobial potential of the probiotic strains was assessed against Staphylococcus aureus and Listeria monocytogenes using extracellular or intracellular fractions of each probiotic previously cultured aerobically or anaerobically. Antioxidant capacity was measured indirectly through a colorimetric assay of iron II. Then anti-inflammatory potential was evaluated in HT29 cells by cytokine quantification. For the first time, this article highlights that all strains studied enhanced their biological activity through fermentative metabolism. As expected, most strains inhibited L. monocytogenes. Among them, Lactobacillus delbruekii subsp. lactis showed the highest biological activity, followed by Lacticaseibacillus rhamnosus and Limosilactobacillus mucosae. These strains also reduced inflammation by 50

This study aimed to evaluate the impact of incorporating yeast cell wall (YCW) into alginate/whey protein (ALG/WP) particles as a strategy to improve oral insulin delivery. Insulin-loaded particles were produced by an extrusion-gelation process with or without YCW, and their physicochemical, mucoadhesive, and permeability properties were assessed in vitro, ex vivo, and in vivo. The inclusion of YCW increased the viscosity of the polymeric solution, resulting in more cohesive particles and a significant reduction in insulin loss during coating. Encapsulation efficiencies ranged from 65 to 99%. However, YCW did not significantly affect particle size or the release mechanism, which remained diffusion-controlled. Although YCW-containing beads exhibited enzyme inhibitory and mucoadhesive properties, insulin protection against enzymatic degradation was similar to that of control beads. YCW moderately enhanced insulin permeability in Caco-2 cell monolayers without cytotoxicity, consistent with a reversible reduction of transepithelial electrical resistance. This effect did not translate into a measurable increase in insulin absorption in ex vivo duodenum or in vivo duodenal administration, indicating that its contribution as an absorption enhancer is limited under physiologically complex conditions.

Lipid-based formulations (LBFs) play a crucial role in enhancing the oral bioavailability of poorly water-soluble drugs by leveraging lipid digestion and solubilization processes. However, developing robust in vitro–in vivo correlations (IVIVCs) for LBFs presents unique challenges due to the complex interplay of digestion, permeation, and dynamic solubilization. This article reviews the construction of IVIVC in the context of LBFs, highlighting the limitations of traditional methods and the need for tailored approaches. It examines the in vitro tools commonly employed for LBF characterization, such as USP dissolution tests, lipolysis assays, and combined models, and discusses their relevance to in vivo performance prediction. The review also explores the sources of in vivo data essential for validating IVIVC and describes the most popular in silico tools for predicting in vivo performance, focusing on lipid-based formulations. This work aims to pave the way for more effective and adaptable IVIVC methodologies for lipid-based drug delivery systems.

This study was focused on one particular case of hot-melt coating with trilaurin – a solid medium-chain monoacid triglyceride. The challenge of using trilaurin as coating agent in melting-based processes is linked to its relatively low melting profile: 15.6°C (Tm,α), 35.1°C (Tm,β′) and 45.7°C (Tm,β). From a process perspective, the only possibility to generate products coated with formulations composed of trilaurin is by setting thermal operational conditions above Tm,α. From a material perspective, this processing possibility depends principally on trilaurin crystallisation which was investigated via a set of analytical techniques including turbidimetry, calorimetry, hot-melt goniometry, and polarised light microscopy. A highly soluble drug model substrate (sodium chloride crystals) was coated with three selected trilaurin-based formulations: (i) trilaurin, (ii) trilaurin plus talc, and (iii) trilaurin plus vitamin E TPGS and talc. Coated salt crystals were then analysed to investigate processing performance, coating quality, stability and release properties under digestion effect. The results show that firstly, talc addition promotes nucleation and crystal growth and, as a consequence, it facilitates the manufacture of trilaurin-based formulations. Secondly, the formulation of a solid triglyceride and a hydrophilic surfactant could potentially cause release instability, but formula (iii) was found to be stabilised by a mechanism whereby trilaurin crystallization enhanced in the presence of talc immobilised vitamin E TPGS in its crystal lattice. Thirdly, talc addition did not significantly influence trilaurin digestion which endows products with an immediate release in lipolytic conditions instead of an extended liberation in pure water. Nor did the addition of one or two additives alter the extent of trilaurin digestion under the conditions studied. These important findings relate to product manufacturability, stability, and release properties. A good understanding of material properties (e.g. crystallisation, polymorphism, digestibility) is essential for melt-processing, lipid coating stabilising and modulation of release profile of solid lipid-coated product, as demonstrated in this case study with trilaurin.

The encapsulation of molecules with different physicochemical properties (theophylline, blue dextran, salicylic acid and insulin) in whey protein (WP) and alginate (ALG) microparticles (MP) for oral administration was studied. MP based on WP/ALG were prepared by a cold gelation technique and coated with WP solution after reticulation. Molecules influenced polymer solution viscosity and elasticity, resulting in differences regarding encapsulation efficiency (from 23 to 100%), MP structure and swelling (>10%) and in terms of pH tested. Molecule release was due to diffusion and/or erosion of MP and was very dependent on the substance encapsulated. All the loaded MP were successfully coated, but variation in coating thickness (from 68 to 146 µm) and function of the molecules encapsulated resulted in differences in molecule release (5 to 80% in 1 h). Gel rheology modification, due to interactions between WP, ALG, calcium and other substances, was responsible for the highlighted differences. Measuring rheologic parameters before extrusion and reticulation appeared to be one of the most important aspects to study in order to successfully develop a vector with optimal biopharmaceutical properties. Our vector seems to be more appropriate for anionic high-molecular-weight substances, leading to high viscosity and elasticity and to MP enabling gastroresistance and controlled release of molecules at intestinal pH.

For pediatric radiological procedures (RP), pentobarbital sodium (PNa) can be used orally or rectally to replace intravenous anesthesia. Since no commercial PNa suppositories exist, they must be prepared by compounding pharmacies. This study aims to develop fast-dissolving PNa suppositories for fast pharmacological activity during RP. We prepared gelatin (G), gelatin/polyethylene glycol 4000 (GP), and polyethylene glycol 4000 (P) suppositories, with and without pH adjustment, and assessed their dosage uniformity (DU), softening time, rupture resistance, and in-vitro dissolution. An optimal formulation was selected, and PNa release was compared to that of fat-based suppositories using dissolution tests. Additionally, the quality control process (analytical performance, safety/eco-friendliness and productivity/practical effectiveness) of these formulas were compared using a RGB method. All hydrophilic formulas (HF) met the DU requirement (AV < 8 %) except for P (AV 15.62 ± 4 %). pH adjustment enhanced G and GP suppositories resistance to 2.2 ± 0.2 kg and 2.0 ± 0.3 kg, respectively, and allowed 100 % release of PNa in under 10 min. In contrast, lipophilic formulas released less than 80 % of PNa at best after 120 min. These results show the biopharmaceutical suitability of HF for RP compared to lipophilic ones, but a pharmacokinetic study is needed to confirm data.

The selection of components within a formulation or for treatment must stop being arbitrary and must be focused on scientific evidence that supports the inclusion of each one. Therefore, the objective of the present study was to obtain a formulation based on ascorbic acid (AA) and Eudragit FS 30D microparticles containing curcumin-boric acid (CUR-BA) considering interaction studies between the active components carried out via Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) to minimize antagonistic effects, and comprehensively and effectively treat turkey poults infected with Salmonella enteritidis (S. enteritidis). The DSC and FTIR studies clearly demonstrated the interactions between AA, BA, and CUR. Consequently, the combination of AA with CUR and/or BA should be avoided, but not CUR and BA. Furthermore, the Eudragit FS 30D microparticles containing CUR-BA (SD CUR-BA MP) showed a limited release of CUR-BA in an acidic medium, but they were released at a pH 6.8-7.0, which reduced the interactions between CUR-BA and AA. Finally, in the S. enteritidis infection model, turkey poults treated with the combination of AA and SD CUR-BA MP presented lower counts of S. enteritidis in cecal tonsils after 10 days of treatment. These results pointed out that the use of an adequate combination of AA and CUR-BA as an integral treatment of S. enteritidis infections could be a viable option to replace the indiscriminate use of antibiotics.

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (−63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS.

Objective To perform the solid-state characterization and the in vitro-in vivo correlation (IVIVC) of three batches of efavirenz (EFV) active pharmaceutical ingredients. Significance EFV is an effective anti-HIV drug. Due to the poor aqueous solubility, the rate and extent of EFV absorption deeply depend on its dissolution characteristics. Methods Thermal analyses, x-ray diffraction, and particle size distribution were performed. The saturation solubility and dissolution profiles were assessed in 0.5% (w/v) sodium lauryl sulfate (SLS), fasted-state simulated intestinal fluid (FaSSIF), and fed-state simulated intestinal fluid (FeSSIF) using a flow-through cell. Each batch was orally administered to Wistar rats and the pharmacokinetic parameters were correlated with those obtained from in vitro dissolution. Results All batches of EFV consisted polymorph I. EFV-A presented the lowest particle size distribution [d(v,0.5) = 197.8 mu m; d(v,0.9) = 444.6 mu m] followed by EFV-B [d(v,0.5) = 223.9 mu m; d(v,0.9) = 481.1 mu m], and EFV-C [d(v,0.5) = 240.8 mu m; d(v,0.9) = 497.3 mu m]. The saturated solubility in FaSSIF was 36% and 40% of that in FeSSIF and SLS, respectively. EFV-A presented the fastest rate and largest extension of dissolution than EFV-B and C (79.15%, 69.93% and 54.22%, respectively, as well as the highest maximum plasma concentration. Levels B, C, and multiple-C of IVIVC models were achieved. Conclusion The FaSSIF medium discriminated the dissolution profiles of EFV APIs. Small differences in particle size distribution had a significant impact on the biopharmaceutical parameters of EFV, suggesting that strict control of such parameter is an important aspect during API development and drug formulation.

The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. 250–300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.