Search Results (33)

Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. Results: The investigations showed that the two S-SNEDDS formulations improved the CBD’s solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex^®) and CBD-MCT), which is favorable for the application of CBD products. Conclusions: SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs. Full article

This study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to improve the oral bioavailability of poorly soluble carvedilol using mesoporous silica nanoparticles (MSNs). The liquid self-nanoemulsifying drug delivery system (L-SNEDDS) consisted of carvedilol, Peceol, Tween 80, and Labrasol in a weight ratio of 10:25:50:25. The liquid SNEDDS was suspended in MSN at various ratios and spray-dried to produce S-SNEDDS. The emulsion size, PDI, solubility, and dissolution of various ratios of MSN were evaluated to make the optimal S-SNEDDS. The optimal S-SNEDDS, manufactured using a ratio of MSN to L-SNEDDS 1000 at 500, formed a nanoemulsion and achieved efficient supersaturation compared to carvedilol alone, which significantly improved drug solubility (approximately 400 times), dissolution (approximately 5.7 times at 60 min), area under the curve (AUC) (21.7 times), and maximum plasma concentration (Cmax) (15.7 times). In addition, the physicochemical properties of the optimal S-SNEDDS were evaluated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR), particle size, and scanning electron microscopy (SEM) images. S-SNEDDS showed a smaller particle size than MSN alone, and the crystalline drug was transformed into an amorphous substance, resulting in encapsulation in MSN. These results suggest that MSN can be a novel biocompatible carrier contributing to a safer and more effective delivery system. Full article

Curcumin, a bioactive compound derived from turmeric, possesses numerous pharmaceutical properties; however, its poor aqueous solubility and permeability result in low bioavailability. This study aims to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) using different lactose types as solid carriers for the oral administration of curcumin to enhance its solubility. The system comprised curcumin, an oil phase, and a surfactant. Jasmine oil, as the oil phase, and Cremophor^® RH40, as the surfactant, were selected due to their superior ability to solubilize curcumin. A microemulsion was then prepared using a ternary phase diagram. The liquid SNEDDSs were converted into S-SNEDDSs by employing three solid carriers: Tablettose^® 80, FlowLac^® 100, and GranuLac^® 200. Dissolution studies conducted in simulated gastric fluid demonstrated a significant improvement in curcumin solubility in the S-SNEDDS formulations compared to curcumin powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed the appearance of curcumin in the S-SNEDDS, while Fourier-transform infrared (FTIR) spectroscopy indicated compatibility between the excipients and curcumin. Additionally, an accelerated stability study conducted over four weeks at 40 °C and 75% relative humidity showed no significant changes in the physical appearance of the S-SNEDDS formulations. These findings suggest that the S-SNEDDS formulation effectively enhances curcumin’s solubility, potentially improving its bioavailability for oral administration. Full article

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS. Full article

Enzalutamide (ENZ), marketed under the brand name Xtandi^® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ’s low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development. Full article

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul^® MCM, Gelucire^® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus^® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes. Full article

Lansoprazole (LZP) is used to treat acid-related gastrointestinal disorders; however, its low aqueous solubility limits its oral absorption. Black seed oil (BSO) has gastroprotective effects, making it a promising addition to gastric treatment regimens. The present study aims to develop a stable multifunctional formulation integrating solid dispersion (SD) technology with a bioactive self-nanoemulsifying drug delivery system (SNEDDS) based on BSO to synergistically enhance LZP delivery and therapeutic effects. The LZP-loaded SNEDDS was prepared using BSO, Transcutol P, and Kolliphor EL. SDs were produced by microwave irradiation and lyophilization using different polymers. The formulations were characterized by particle apparent hydrodynamic radius analysis, zeta potential, SEM, DSC, PXRD, and in vitro dissolution testing. Their chemical and physical stability under accelerated conditions was also examined. Physicochemical characterization revealed that the dispersed systems were in the nanosize range (<500 nm). DSC and PXRD studies revealed that lyophilization more potently disrupted LZP crystallinity versus microwave heating. The SNEDDS effectively solubilized LZP but degraded completely within 1 day. Lyophilized SDs with Pluronic F-127 demonstrated the highest LZP dissolution efficiency (3.5-fold vs. drug) and maintained chemical stability (>97%) for 1 month. SDs combined with the SNEDDS had variable effects suggesting that the synergistic benefits were dependent on the formulation and preparation method. Lyophilized LZP-Pluronic F127 SD enabled effective and stable LZP delivery alongside the bioactive effects of the BSO-based SNEDDS. This multifunctional system is a promising candidate with the potential for optimized gastrointestinal delivery of LZP and bioactive components. Full article

Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm⁻¹), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations. Full article

3D printing technology in medicine is gaining great attention from researchers since the FDA approved the first 3D-printed tablet (Spritam^®) on the market. This technique permits the fabrication of various types of dosage forms with different geometries and designs. Its feasibility in the design of different types of pharmaceutical dosage forms is very promising for making quick prototypes because it is flexible and does not require expensive equipment or molds. However, the development of multi-functional drug delivery systems, specifically as solid dosage forms loaded with nanopharmaceuticals, has received attention in recent years, although it is challenging for formulators to convert them into a successful solid dosage form. The combination of nanotechnology with the 3D printing technique in the field of medicine has provided a platform to overcome the challenges associated with the fabrication of nanomedicine-based solid dosage forms. Therefore, the major focus of the present manuscript is to review the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology. Utilization of 3D printing techniques in the field of nanopharmaceuticals achieved the successful transformation of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) to solid dosage forms such as tablets and suppositories easily with customized doses as per the needs of the individual patient (personalized medicine). Furthermore, the present review also highlights the utility of extrusion-based 3D printing techniques (Pressure-Assisted Microsyringe—PAM; Fused Deposition Modeling—FDM) to produce tablets and suppositories containing polymeric nanocapsule systems and SNEDDS for oral and rectal administration. The manuscript critically analyzes contemporary research related to the impact of various process parameters on the performance of 3D-printed solid dosage forms. Full article

Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations achieves higher drug loading and potentially improves solubilisation and bioavailability. However, for the weak base blonanserin, silica solidified supersaturated lipid-based formulations have demonstrated reduced in vitro solubilisation compared to their liquid-state counterparts. Therefore, this study aimed to understand the influence of supersaturated drug load on blonanserin solubilisation from liquid and silica solidified supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis. Stable liquid super-SNEDDS with varying drug loads (90–300% of the equilibrium solubility) were solidified by imbibition into porous silica microparticles (1:1 lipid: silica ratio). In vitro lipolysis revealed greater blonanserin solubilisation from liquid super-SNEDDS compared to solid at equivalent drug saturation levels, owing to strong silica-BLON/lipid interactions, evidenced by a significant decrease in blonanserin solubilisation upon addition of silica to a digesting liquid super-SNEDDS. An increase in solid super-SNEDDS drug loading led to increased solubilisation, owing to the increased drug:silica and drug:lipid ratios. Solidifying SNEDDS with silica enables the fabrication of powdered formulations with higher blonanserin loading and greater stability than liquid super-SNEDDS, however at the expense of drug solubilisation. These competing parameters need careful consideration in designing optimal super-SNEDDS for pre-clinical and clinical application. Full article

Background: Solidification by high surface area adsorbents has been associated with major obstacles in drug release. Accordingly, new approaches are highly demanded to solve these limitations. The current study proposes to improve the drug release of solidified self-nanoemulsifying drug delivery systems (SNEDDS) to present dual enhancement of drug solubilization and formulation stabilization, using cinnarizine (CN) as a model drug. Methods: The solidification process involved the precoating of adsorbent by lyophilization of the aqueous dispersion of polymer–adsorbent mixture using water as a green solvent. Then, the precoated adsorbent was mixed with drug-loaded liquid SNEDDS to prepare solid SNEDDS. The solid-state characterization of developed cured S-SNEDDS was done using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro dissolution studies were conducted to investigate CN SNEDDS performance at pH 1.2 and 6.8. The solidified formulations were characterized by Brunauer–Emmett–Teller (BET), powder flow properties, scanning electron microscopy, and droplet size analysis. In addition, the optimized formulations were evaluated through in vitro lipolysis and stability studies. Results: The cured solid SNEDDS formula by PVP k30 showed acceptable self-emulsification and powder flow properties. XRD and DSC revealed that CN was successfully amorphized into drug-loaded S-SNEDDS. The uncured solid SNEDDS experienced negligible drug release (only 5% drug release after 2 h), while the cured S-SNEDDS showed up to 12-fold enhancement of total drug release (at 2 h) compared to the uncured counterpart. However, the cured S- SNEDDS showed considerable CN degradation and decrease in drug release upon storage in accelerated conditions. Conclusions: The implemented solidification approach offers a promising technique to minimize the adverse effect of adsorbent on drug release and accomplish improved drug release from solidified SNEDDS. Full article

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box–Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required. Full article

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, −26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs. Full article

Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of −19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH. Full article

The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in M_w. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems. Full article