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.

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 aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98–100% of drug release in 30–45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

The main objective of this research work was the development and evaluation of transfersomes integrated oral films for the bioavailability enhancement of Ebastine (EBT) to treat allergic rhinitis. The flexible transfersomes, consisting of drug (EBT), lipid (Phosphatidylcholine) and edge activator (EA) Polyoxyethylene sorbitan monooleate or Sorbitan monolaurate, were prepared with the conventional thin film hydration method. The developed transfersomes were further integrated into oral films using the solvent casting method. Transfersomes were evaluated for their size distribution, surface charge, entrapment efficiency (EE%) and relative deformability, whereas the formulated oral films were characterized for weight, thickness, pH, folding endurance, tensile strength, % of elongation, degree of crystallinity, water content, content uniformity, in vitro drug release and ex vivo permeation, as well as in vivo pharmacokinetic and pharmacodynamics profile. The mean hydrodynamic diameter of transfersomes was detected to be 75.87 ± 0.55 nm with an average PDI and zeta potential of 0.089 ± 0.01 and 33.5 ± 0.39 mV, respectively. The highest deformability of transfersomes of 18.52 mg/s was observed in the VS-3 formulation. The average entrapment efficiency of the transfersomes was about 95.15 ± 1.4%. Transfersomal oral films were found smooth with an average weight, thickness and tensile strength of 174.72 ± 2.3 mg, 0.313 ± 0.03 mm and 36.4 ± 1.1 MPa, respectively. The folding endurance, pH and elongation were found 132 ± 1, 6.8 ± 0.2 and 10.03 ± 0.4%, respectively. The ex vivo permeability of EBT from formulation ETF-5 was found to be approximately 2.86 folds higher than the pure drug and 1.81 folds higher than plain film (i.e., without loaded transfersomes). The relative oral bioavailability of ETF-5 was 2.95- and 1.7-fold higher than that of EBT-suspension and plain film, respectively. In addition, ETF-5 suppressed the wheal and flare completely within 24 h. Based on the physicochemical considerations, as well as in vitro and in vivo characterizations, it is concluded that the highly flexible transfersomal oral films (TOFs) effectively improved the bioavailability and antihistamine activity of EBT.