Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs.

The low aqueous solubility of many drugs reduces their bioavailability in the blood. Oils have been used for centuries to enhance the solubility of drugs; however, they can disturb the lipid profile of the patients. In this study, self-nanoemulsifying drug delivery systems of omega-3 fatty acids-rich oils are prepared and optimized for the delivery of lipophilic drugs. Rosuvastatin, a potent hypolipidemic drug, was used as a model lipophilic drug. Fish oil showed more than 7-fold higher solubility of rosuvastatin than other oils and therefore it was selected for the development of self-nanoemulsifying drug delivery systems (SNEDDS). Different combinations of surfactants and co-surfactants were screened and a surfactant mixture of Tween 80 (surfactant) and Capryol PGMC (cosurfactant) were selected for compatibility with fish oil and rosuvastatin. A pseudoternary phase diagram of oil, surfactant, and co-surfactant was designed to identify the emulsion region. The pseudoternary phase diagram predicted a 1:3 oil and surfactant mixture as the most stable ratio for the emulsion system. Then, a response-surface methodology (Box-Behnken design) was applied to calculate the optimal composition. After 17 runs, fish oil, Tween 80, and Capryol PGMC in proportions of 0.399, 0.67, and 0.17, respectively, were selected as the optimized formulation. The self-nanoemulsifying drug delivery systems showed excellent emulsification potential, robustness, stability, and drug release characteristics. In the drug release studies, SNEDDS released 100% of the payload in around 6 h whereas, release of the plain drug was less than 70% even after 12 h. Therefore, omega-3 fatty acids-rich healthy lipids have enormous potential to enhance the solubility of lipophilic drugs whereas, self-emulsification can be used as a simple and feasible approach to exploit this potential.

Corrigendum: Chitosan/Xanthan Gum based hydrogels as potential carrier for an antiviral drug: Fabrication, characterization, and safety evaluation.

[This corrects the article DOI: 10.3389/fchem.2020.00050.].

Chitosan/Xanthan Gum Based Hydrogels as Potential Carrier for an Antiviral Drug: Fabrication, Characterization, and Safety Evaluation.

This study investigated the use of pure polymer chitosan (CS), xanthan gum (XG), monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and initiator potassium persulfate (KPS) as drug carrier system crosslinked through N' N'-methylene bis-acrylamide (MBA) for controlled drug delivery of acyclovir (ACV). ACV is highly effective and selective antiviral drugs used for prophylaxis and treatment against herpes simplex viruses (HSV) infections. Present oral marketed formulations are associated with number of side effects and shortcomings which hampered its clinical effectiveness. Hydrogels (FCX1-FCX9) composed of CS, XG, AMPS, MBA, and KPS were prepared by free radical polymerization technique and characterized through FTIR, PXRD, thermal analysis and SEM. Swelling dynamics and drug release behavior was also investigated. FTIR studies confirmed that ACV was successfully encapsulated into hydrogel polymeric network. SEM revealed porous structure whereas thermal analysis showed enhanced thermal stability of polymeric network. PXRD indicated amorphous dispersion of ACV during preparation process. Swelling dynamics and ACV release behavior from developed hydrogels was dependent on pH of the medium and concentration of pure reactants used. Korsmeyer-Peppas model was best fit to regression coefficient. The present work demonstrated a potential for developing a pH sensitive hydrogel for an antiviral drug ACV by using pure polymers CS, XG, and monomer AMPS.

Synthesis and evaluation of topical hydrogel membranes; a novel approach to treat skin disorders.

The aim of the study was to synthesize and evaluate chitosan-based topical cross-linked hydrogel membranes of mupirocin for new pharmaceutical controlled release application. These cross-linked structured membranes were synthesized by modification of free radical polymerization. Low molecular weight (LMW) chitosan is cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with a crosslinker N,N-methylenebisacrylamide (MBA). Hydrogel membranes were characterized by FTIR, DSC, TGA, SEM, Swelling behavior, sol-gel analysis, in vitro percent drug release at different pH, permeation across skin, ex vivo drug deposition study, irritation study and in vivo antibacterial activity of mupirocin loaded hydrogels. Developed membranes were spherical, adhesive and have good elastic strength. FTIR confirmed the cross-linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Drug release through rabbit's skin was evaluated by Franz diffusion cell and up to 6329.61 µg/1.5 cm2 was permeated and drug deposition in skin revealed significant retention up to 1224 µg/1.5 cm2. Formulated membranes were nonirritant to the skin as validated by Draize patch test. In surgical wound model, LMW chitosan-based hydrogel membranes showed prolong efficacy against bacterial infection caused by S. aureus. Enhanced retention of drug in skin demonstrated the good potential of topical delivery for skin bacterial infection.

Development and evaluation of eudragit based microparticles of dexibuprofen for site specific drug release.

The main purpose of work was to formulate dexibuprofen loaded eudragit L-100 micro particles to acquire site specific delivery of dexibuprofen. Micro particles were formulated by an emulsion solvent evaporation method. Four formulations F1, F2, F3 and F4 having drug to polymer ratio 1:1, 1:2, 1:3 and 1:4, respectively were prepared and characterized. The rheological properties manifested that micro particles were worthy for further pharmaceutical exploitation. No notable drug polymer interaction was perceived in FT-IR spectroscopy. SEM micrographs showed rough surface of micro particles. The resulting micro particles had high entrapment efficiency greater than 70%. The in vitro dexibuprofen release at pH 1.2 exhibited poor drug release with less than 21% while at pH 6.8, 60% of the dexibuprofen was released up till 8th hour. The dexibuprofen release was modified by altering polymer concentration in the formulation. The subsequent micro particles were found to be best fit with zero-order release model. Micro particles were efficiently formulated with a focus to release the drug majorly in small intestine. With increase of polymer concentration enhanced entrapment efficiency and decelerated dexibuprofen release from the micro particles has been achieved. In vitro dexibuprofen studies verified the gastro-resistant property of micro particles thus qualify site specific release in gastrointestinal tract.

Synthesis of ß-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

OBJECTIVE: This study was aimed to enhance aqueous solubility of dexibuprofen through designing ß-cyclodextrin (ßCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. SIGNIFICANCE: Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. METHODS: ßCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared ßCD hydrogel nanoparticles. RESULTS: ßCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in ßCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. CONCLUSIONS: The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic ßCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.