Background: Delivering plant extract at high loading with intact antioxidants and efficient skin permeation always remains a challenge. To address this, we prepared a stable gel formulation containing nanoethosomes loaded with Achillea millefolium L. (AM) extract for topical drug delivery.Method: The AM extract was tested at first for phytochemical analysis, antioxidant activity, total phenolic and flavonoid content, and FTIR examination. The nanoethosomes containing AM extract were synthesized and characterized by size, surface charge, and morphology, and entrapment efficiency (EE) was determined. The optimized nanoethosomes were then incorporated to develop a topical gel formulation and subjected to skin for permeation, pH, viscosity, and organoleptic evaluation for up to three months.Results: The AM ethanolic extract demonstrated 88% free radical scavenging activity and notable phenolic and flavonoid contents of up to 123 mg GAE/g and 42 mg QE/g, respectively. The optimized nanoethosomes encapsulated with AM extract (240 nm) were spherical in shape, with −31.1 mV of surface charge, and showed considerable entrapment efficiency (90%). Furthermore, the selected topical gel remained stable during the study period. The Exvivo permeation study of ethosomal gel showed the highest release percentage of 79.8%.Conclusion: The study concludes that topical gel loaded with nanoethosomes containing AM extract is an encouraging approach for topical drug delivery.

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Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodologyFor preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y 1 ), entrapment efficiency (Y 2 ) and drug release (Y 3 ). SLMs having a 10-40 µm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y 1 (29-86 %), Y 2 (45-83 %) and Y 3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer-Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Purpose: To formulate, characterize and optimize nebivolol-loaded sustained release lipospheres (LPs) using beeswax (BW) as the drug carrier. Methods: Nebivolol-loaded LPs were formulated using solvent evaporation technique (SET) and characterized. The impact of independent variables on responses such as percentage yield (PY), entrapment efficiency (EE) and drug release after 12 h (DR12) was assessed using central composite design (CCD). Numerical and graphical optimization techniques were also used to evaluate outcomes of the measured responses. Results: Twenty micron-sized (20-100 µm), smooth spherical LPs with good rheological properties were produced. The yield ranged from 33 (F10) to 81 % (F6), while EE ranged from 32 (F4 and F9) to 69 % (F6). The results of rheological evaluation revealed angle of repose > 24 o, Hausner's ratio > 1.5, and Carr's index ranging from 13 to 19 %. Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and x-ray diffraction (XRD) revealed nebivolol and BW compatibility, and the absence of possible interactions between formulation components. Duration of nebivolol release was strongly associated with BW concentration and formulation F15 showed minimum drug release (46 %). Drug release was significantly higher in formulations with similar BW concentrations and low Tween-20 (T-20) concentrations (F1 and F11) than in formulations with high T-20 concentrations (F2, p < 0.05). The zeta potential of deflocculated LPs ranged from +15 to +35 mV. Nebivolol release (46-85 %) at pH 6.8 was significantly affected by BW concentration and it followed zero order model. Conclusion: The results obtained in this study have shown that BW is a suitable material for producing an effective sustained release formulation. The mechanism of drug release in nebivolol-loaded LPs is diffusion accompanied by erosion.

The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous hydrogels of mefenamic acid were formulated by employing the gas blowing method. The central composite rotatable design (CCRD) was applied to optimize the effect of independent formulation factors like acrylic acid (AC), HPMC and glycerol (GLY) over dependent variables like porosity, viscosity, drug content and swelling ratio of superporous hydrogels in water, phosphate buffer (pH 6.8) and in 0.1N HCl (pH 1.2). A number of characteristics such as void fraction, surface morphology by Scanning electron microscopy (SEM) and in vitro drug release study were governed along with physico-chemical analysis by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and appraised statistically by employing the ANOVA. The comparative analgesic activity of optimized superporous hydrogel formulation SPH17 was also analyzed by using tail flick method. The Fourier transform infrared spectroscopy and Differential scanning calorimetry studies approved the physical compatibility between the polymers and the drug. The Scanning electron microscopy study specified micrographic insight about the structure of formed formulations comprising presence of pores, fibers and drug-hole aggregates. The superporous hydrogels were detected to be low dense as they expressed density lower than 0.75 g/cc. The decrease in concentration of the polymers and cross linker contributed towards the increase in the void fraction of the superporous hydrogel formulations. The optimized formulation SPH 17 exhibited a highly sustained release of MA for up to 10 h in the both 0.1 N HCl and phosphate buffer (66.6%) media. The non-fickian release of drug revealed the coupling of the diffusion and polymer relaxation mechanism of the drug release from the formulations. The obtained outcomes suggested that analgesic effect of SPH 17 was significantly (p &lt; 0.05) higher than that of simple suspension of mefenamic acid and total analgesic effect duration for superporous hydrogel was also doubled as compared to the duration of analgesic effect produced by drug suspension. The successfully formulated SPH with HPMC K100M as a gelling agent had sustained the action of the mefenamic acid (MF) by improving its poor solubility and permeability. The introduction of inter-penetrating polymeric network (acrylic acid) using glycerol as a cross linker impart increased residence time to superporous hydrogels which ultimately enhanced the feasibility of using superporous hydrogel as oral sustained release devices particularly for gastric retention.

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The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (−16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against Candida albicans, the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients’ adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.