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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.

Metabolic syndrome is an associated condition that occurs together and increases the risk of heart disease and diabetes. These conditions include high blood pressure, high blood sugar, and high body mass index (BMI) in terms of cholesterol and triglyceride levels. Most of the elderly population may administer three drugs to control the above conditions. Therefore, this study aims to develop an analytical assay for the precise analysis of three components and to formulate a Self-Nanoemulsifying Drug-Delivery System (SNEDDS) loaded with three drugs: Rosuvastatin Calcium (RC; antilipidemic), Glibenclamide (GB; antidiabetic), and Candesartan Cilexetil (CC; antihypertensive). A design of the experiment was developed at a level of 32, and the influence of column temperature and flow rate was studied in terms of retention time, peak area, peak asymmetry, and resolution. The assay was subjected to several studies to ensure its validation. Under the optimized conditions—column temperature at 50 °C and flow rate at 0.25 mL/min—the three drugs, RC, GB, and CC, are separated. Their retention times are 0.840, 1.800, and 5.803 min, respectively. The assay was valid in terms of linearity, accuracy, and precision. Moreover, the developed assay shows a good tolerance against any change in the condition. The assay was tested also to separate the drugs in a pharmaceutical formulation as SNEDDs. The assay successfully separates the drug with a good resolution.

The development of analytical procedures capable of simultaneous determination of two or more drugs is in crucial demand due to the availability of different formulations that are composed of different APIs. The presented study aimed to optimize and validate a simple, accurate, and sensitive UPLC analytical method for the simultaneous determination of thymoquinone (TQ) and Glibenclamide (GB) using response surface methodology, and apply this method in pharmaceutical formulations. A 32 full design of experiment was utilized to study the impacts of the independent parameters (acetonitrile ACN concentration, A; and column temperature, B) on the drugs’ analytical attributes (viz, retention time, peak area, and peak asymmetry, in addition to the resolution between TQ and GB peaks). The results revealed that the independent parameters exhibited highly significant (p < 0.05) antagonistic effects on retention times for TQ and GB peaks, in addition to the agnostic effect on GB peak symmetry (p-value = 0.001). Moreover, antagonistic impacts (p < 0.05) on the resolution between TQ and GB peaks were found for both independent factors (A and B). The statistical software suggested 46.86% of ACN (A) and 38.80 °C for column temperature (B) for optimum analytical responses. The optimized green method was discovered to be acceptable in terms of selectivity, precision, accuracy, robustness, sensitivity, and specificity. Moreover, the optimized simultaneous method was successfully able to determine the contents of TQ and GB in self-nanoemulsifying drug delivery (SNEDD) formulation, in which the results showed that GB and TQ content within the prepared formulations were 1.54 ± 0.023 and 3.62 ± 0.031 mg/gm, respectively. In conclusion, the developed assay was efficient and valid in analyzing TQ and GB simultaneously in bulk and self-nanoemulsifying drug delivery system (SNEDDs) formulations.

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 (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.

Objective Ginger (Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund’s adjuvant (FCA)-immunized arthritic rats. Methods 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1 ml = 100 µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25 mg/kg b.w for 3 weeks at two different time points. Results Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-β, TNF-α, IL-1β, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-β, TNF-α, IL-1β, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment. Discussion Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.

Gefitinib (GEF) is utilized in clinical settings for the treatment of metastatic lung cancer. However, premature drug release from nanoparticles in vivo increases the exposure of systemic organs to GEF. Herein, nanostructured lipid carriers (NLC) were utilized not only to avoid premature drug release but also due to their inherent lymphatic tropism. Therefore, the present study aimed to develop a GEF-NLC as a lymphatic drug delivery system with low drug release. Design of experiments was utilized to develop a stable GEF-NLC as a lymphatic drug delivery system for the treatment of metastatic lung cancer. The in vitro drug release of GEF from the prepared GEF-NLC formulations was studied to select the optimum formulation. MTT assay was utilized to study the cytotoxic activity of GEF-NLC compared to free GEF. The optimized GEF-NLC formulation showed favorable physicochemical properties: 90% entrapment efficiency. Interestingly, the prepared formulation was able to retain GEF with only ≈57% drug release within 24 h. Furthermore, GEF-NLC reduced the sudden exposure of cultured cells to GEF and produced the required cytotoxic effect after 48 and 72 h incubation time. Consequently, optimized formulation offers a promising approach to improve GEF’s therapeutic outcomes with reduced systemic toxicity in treating metastatic lung cancer.

This study was conducted to formulate, characterize, and investigate the bioavailability of hydrocortisone (HCT) when prepared as solid dispersions. HCT was mixed in an organic solvent with polyethylene glycol 4000 (PEG 4000) and Kolliphor® P 407. Spray drying technique was employed to form a solid dispersion formulation at a specific ratio. Physical and chemical characterization of the formed particles were achieved using differential scanning calorimetry, scanning electron microscopy, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. Furthermore, comparative in vitro and in vivo studies were conducted between the formulated particles against neat HCT. The formulated solid dispersion showed elongated particles with leaf-like structure. Formation of new chemical bonds in the formed particle was suggested due to the change in the vibrational wave numbers and the significant improvement in the bioavailability of the dispersed particles proved the importance of this technique. Keywords: Hydrocortisone, Solid dispersion, Spray drying, Low potency, Bioavailability, PEG 4000, Kolliphor® P 407

Purpose: Ramipril (RMP)—an angiotensin-converting enzyme (ACE) inhibitor—and thymoquinone (THQ) suffer from poor oral bioavailability. Developing a combined liquid SNEDDS that comprises RMP and black seed oil (as a natural source of THQ) could lead to several formulations and therapeutic benefits. Methods: The present study involved comprehensive optimization of RMP/THQ liquid SNEDDS using self-emulsification assessment, equilibrium solubility studies, droplet size analysis, and experimentally designed phase diagrams. In addition, the optimized RMP/THQ SNEDDS was evaluated against pure RMP, pure THQ, and the combined pure RMP + RMP-free SNEDDS (capsule-in-capsule) dosage form via in vitro dissolution studies. Results: The phase diagram study revealed that black seed oil (BSO) showed enhanced self-emulsification efficiency with the cosolvent (Transcutol P) and hydrogenated castor oil. The phase diagram studies also revealed that the optimized formulation BSO/TCP/HCO-30 (32.25/27.75/40 % w/w) showed high apparent solubility of RMP (25.5 mg/g), good THQ content (2.7 mg/g), and nanometric (51 nm) droplet size. The in-vitro dissolution studies revealed that the optimized drug-loaded SNEDDS showed good release of RMP and THQ (up to 86% and 89%, respectively). Similarly, the isolation between RMP and SNEDDS (pure RMP + RMP-free SNEDDS) using capsule-in-capsule technology showed >84% RMP release and >82% THQ release. Conclusions: The combined pure RMP + RMP-free SNEDDS (containing black seed oil) could be a potential dosage form combining the solubilization benefits of SNEDDSs, enhancing the release of RMP/THQ along with enhancing RMP stability through its isolation from lipid-based excipients during storage.

The urinary bladder stores urine until the time of urination. Systemic administration of drugs to treat bladder diseases faces several limitations. Therefore, intravesical drug delivery is a promising alternative route of administration. An in-situ gel is used to form a gel inside the bladder cavity and ensure continuous release of the drug even after urination. The objective of the present study was to optimize an in-situ gel formulation of poloxamer and chitosan for intravesical delivery of ketorolac tromethamine. The gelling temperature of the prepared combinations ranged from 20.67 to 25.8 °C. In-vitro release of KT was sustained for up to 7 h using a poloxamer concentration ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%. Design-Expert® 10 was used to select the optimized formulation (poloxamer/chitosan 17/1.589% w/w) which significantly (p

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl® and Neusilin® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification.