Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity. Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model. Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity. Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.

The goal of this investigation was to determine the effectiveness of hydrophilic polymers in preparing a solid dispersion to enhance the solubility and dissolution of poorly water-soluble drugs, such as curcumin. In order to prepare the solid dispersion, curcumin was uniformly distributed in the polymeric matrix of polyethylene glycol (PEG 6000), hydroxypropyl methyl cellulose (HPMC E5), polyvinyl pyrrolidine (PVP K30), and bovine serum albumin (BSA) using the kneading and solvent evaporation methods. The developed dispersion formulations were characterized for solubility, dissolution, Fourier transform infrared (FTIR), X-ray diffractometry (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Attaining enhanced physical stability with solubility is crucial in the selection of suitable polymer types and ratios. The optimized HPMC E5 and PVP based dispersion displayed 4.3 and 2.8 times greater solubility compared to the pure drug, respectively. The SEM also showed the optimized HPMC-based dispersion was smoother in comparison to the PVP-based dispersion. The XRD and DSC validated the successful modification of the crystal structure of curcumin resulting in the enhancement of its solubility and dissolution. In conclusion, the HPMC E5 formulation was the optimal candidate to create solid amorphous dispersions of curcumin, which might be employed as an effective delivery system.

Glimepiride (GMP), an oral hypoglycemic agent is extensively employed in the treatment of type 2 diabetes. Transdermal delivery of GMP has been widely investigated as a promising alternative to an oral approach but the delivery of GMP is hindered owing to its low solubility and permeation. The present study was designed to formulate topical nanoemulgel GMP system and previously reported solubility enhanced glimepiride (GMP/βCD/GEL-44/16) in combination with anti-diabetic oil to enhance the hypoglycemic effect. Nanoemulsions were developed using clove oil, Tween-80, and PEG-400 and were gelled using xanthan gum (3%, w/w) to achieve the final nanoemulgel formulations. All of the formulations were evaluated in terms of particle size, zeta potential, pH, conductivity, viscosity, and in vitro skin permeation studies. In vivo hypoglycemic activity of the optimized nanoemulgel formulations was evaluated using a streptozocin-induced diabetes model. It was found that a synergistic combination of GMP with clove oil improved the overall drug permeation across the skin membrane and the hypoglycemic activity of GMP. The results showed that GMP/βCD/GEL-44/16-loaded nanoemulgel enhanced the in vitro skin permeation and improved the hypoglycemic activity in comparison with pure and marketed GMP. It is suggested that topical nano emulsion-based GMP gel and GMP/βCD/GEL-44/16 could be an effective alternative for oral therapy in the treatment of diabetes.

The study aimed to translate and validate the Arabic version of General Medication Adherence Scale (GMAS) in Saudi patients with chronic diseases. A multi-center cross sectional study was conducted for a month in out-patient wards of hospitals in Khobar, Dammam, Makkah, and Madinah, Saudi Arabia. Patients were randomly selected from a registered patient pools at hospitals and the item-subject ratio was kept at 1:20. The tool was assessed for factorial, construct, convergent, known group and predictive validities as well as, reliability and internal consistency of scale were also evaluated. Sensitivity, specificity, and accuracy were also evaluated. Data were analyzed using SPSS v24 and MedCalc v19.2. The study was approved by concerned ethics committees (IRB-129-25/6/1439) and (IRB-2019-05-002). A total of 282 responses were received. The values for normed fit index (NFI), comparative fit index (CFI), Tucker Lewis index (TLI) and incremental fit index (IFI) were 0.960, 0.979, 0.954 and 0.980. All values were >0.95. The value for root mean square error of approximation (RMSEA) was 0.059, i.e., 0.7, that established convergent validity. Known group validity was established by obtaining significant p-value 0.7. Predictive validity was established by evaluating odds ratios (OR) of demographic factors with adherence score using logistic regression. Sensitivity was 78.16%, specificity was 76.85% and, accuracy of the tool was 77.66%, i.e., >70%. The Arabic version of GMAS achieved all required statistical parameters and was validated in Saudi patients with chronic diseases.

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m²/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD₅₀ of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.

Poor solubility is the major challenge involved in the formulation development of new chemical entities (NCEs), as more than 40% of NCEs are practically insoluble in water. Solid dispersion (SD) is a promising technology for improving dissolution and, thereby, the bioavailability of poorly soluble drugs. This study investigates the influence of a pH-sensitive acrylate polymer, EPO, on the physicochemical properties of rosuvastatin calcium, an antihyperlipidemic drug. In silico docking was conducted with numerous polymers to predict drug polymer miscibility. The screened-out polymer was used to fabricate the binary SD of RoC in variable ratios using the co-grinding and solvent evaporation methods. The prepared formulations were assessed for physiochemical parameters such as saturation solubility, drug content and in vitro drug release. The optimized formulations were further ruled out using solid-state characterization (FTIR, DSC, XRD and SEM) and in vitro cytotoxicity. The results revealed that all SDs profoundly increased solubility as well as drug release. However, the formulation RSE-2, with a remarkable 71.88-fold increase in solubility, presented 92% of drug release in the initial 5 min. The molecular interaction studied using FTIR, XRD, DSC and SEM analysis evidenced the improvement of in vitro dissolution. The enhancement in solubility of RoC may be important for the modulation of the dyslipidemia response. Therefore, pharmacodynamic activity was conducted for optimized formulations. Our findings suggested an ameliorative effect of RSE-2 in dyslipidemia and its associated complications. Moreover, RSE-2 exhibited nonexistence of cytotoxicity against human liver cell lines. Convincingly, this study demonstrates that SD of RoC can be successfully fabricated by EPO, and have all the characteristics that are favourable for superior dissolution and better therapeutic response to the drug.