Improvement of effect of water-in-oil microemulsion as an oral delivery system for fexofenadine: in vitro and in vivo studies

Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In this work, novel FEX loaded water in oil microemulsion (w/o) was designed to improve bioavailability and compared with Fexofen® syrup in in vitro and in vivo studies. In addition, pharmacokinetic parameters in permeability studies were estimated by using WinNonLin software program. w/o microemulsion system was optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68 (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture; oil and cosurfactant was developed for oral drug delivery. w/o microemulsion systems were characterized by phase behavior, particle size, viscosity and solubilization capacity. In vitro studies were studied using Caco-2 cell monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in rabbits and compared to Fexofen® syrup. Fexofen® syrup and microemulsion were administered by oral gavage at 6 mg/kg of the same concentration. The experimental results indicated that microemulsion (HLB = 5.53) formed nanometer sized droplets (33.29 ± 1.76) and had good physical stability. This microemulsion increased the oral bioavailability of FEX which was highly water-soluble but fairly impermeable. The relative bioavailability of FEX microemulsion was about 376.76% compared with commercial syrup in rabbits. In vitro experiments were further employed for the enhanced effect of the microemulsion for FEX. These results suggest that novel w/o microemulsion plays an important role in enhancing oral bioavailability of low permeability drugs

Dizaj i statistička optimizacija liposfera s glipizidom pomoću metodologije odgovora površine

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 ± 1.38 µm, 86.28 ± 1.32 %, 77.23 ± 2.78 % and 5.60 ± 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.32 faktorijalni dizajn primijenjen je za pripravu liposfera s glipizidom metodom separacije pomoću emulzija koristeći parafinski vosak i starinsku kiselinu kao tvari za usporavanje. Pomoću F-testa praćen je učinak kritičnih varijabli tijekom formuliranja, tj. količina parafinskog voska (X1) i udio stearinske kiseline (X2) na srednji promjer liposfera (dg), postotak inkapsulirane ljekovite tvari (% EE), oslobađanje ljekovite tvari nakon 12 h (rel12) te vrijeme potrebno za oslobađanje 50% ljekovite tvari (t50). Pomoću multiple linearne regresijske analize (MLRA) i analize varijabli (ANOVA) za svaki su parametar načinjeni matematički modeli koji sadrže samo značajne varijable. Proučavanje varijabli na oba načina ukazalo je na njihov značajan utjecaj (p < 0,05) na parametre liposfera. Postavljanjem ograničenja na zavisne i nezavisne varijable provedena je numerička optimizacija na principu poželjnosti. Eksperimentalne vrijednosti dg, % EE, rel12 i t50 optimiziranih formulacija bile su 57,54 ± 1,38 µm, 86,28 ± 1,32%, 77,23 ± 2,78% i 5,60 ± 0,32 h. Dobivene eksperimentalne vrijednosti iznosile su vrlo slične vrijednostima predviđenim matematičkim modelima. Oslobađanje glipizida iz liposfera slijedio je kinetiku prvog reda i okarakterizirano je Higuchijevim difuzijskim modelom. Optimizirane liposfere su nakon peroralne primjene na štakorima pokazale produljeni antidijabetički učinak

Classification and application of colloidal drug delivery systems: Passive or active tumor targeting

[No abstract available

Places of microemulsion and emulsion in cancer therapy: In vitro and in vivo evaluation

Cancer is one of the most challenging health problems of the developing world. Cancer is actually a heterogenic group of disease which is mainly characterized by altered cell growth and apoptotic systems within the cell. All carcinogens or mutagens cause some damage to the DNA of the cell. This alteration may be in a wide pattern ranging from a single base pair mutation to chromosomal aberrations. The DNA mutations that are not repaired before the next cell division cycle pass on to the daughter cells and thus result in the accumulation of DNA mutations in the nucleus. All scientific studies on carcinogenesis show that cancer is a genetic disease caused by means of molecular change [1,2]. © 2009 by Taylor & Francis Group, LLC

Permeation studies and histological examination of sheep nasal mucosa following administration of different nasal formulations with or without absorption enhancers

PubMed ID: 18446567This study was designed to investigate the possible histological effects of different intranasal (IN) formulations of indomethacin (IND) on nasal mucosa in sheep. For this purpose, oil-in-water (O/W) emulsion (E) and solution (S) formulations including 3 mg/mL of IND were prepared. Penetration enhancers such as polyvinylpyrolidone (PVP), citric acid (CA) and sodium taurocholate (NaT) were added to emulsion (1%) at the final step into the formulations. First, the effect of penetration enhancers on permeation of IND was evaluated by in vitro permeation studies in which sheep nasal mucosa was used. According to the permeation studies PVP showed the highest enhancing effect on the permeation rate of IND from sheep nasal mucosa. Furthermore, the IND permeation from E containing PVP (1.624 ± 0.045 mg) was significantly higher than that obtained from E (0.234 ± 0.012 mg) (p < 0.05). For the histological studies, white Karaman sheep of approximately 20 ± 5 kg, aged 4 to 8 months were used. They were randomly divided into eight groups, each including three sheep. Five experimental groups received different formulations of IND emulsion without/ with penetration enhancers (E-PVP, E-CA, E-NaT, E) and IND solution (S), respectively. Parallel controls were composed of either untreated groups and were given blank emulsion or isotonic sodium chloride solution (0.31 mg/kg). 2 mL of each experimental formulation was applied to both nostrils of sheep, and 1/3 central and lower regions of the nose were dissected and prepared for light microscopy. Specimens stained with hematoxylin and eosin and Gomori's trichrome were examined by light microscopy. No signs of inflammation or erosion were noticed in the nasal mucosa of the control groups. Widened epithelial intercellular spaces were noticed in E-CA, E-NaT, and E-PVP groups as well with the E-PVP group showing the largest intraepithelial separations. E-CA and E-NaT groups showed significant decrease in the amount of goblet cells, while hypoplasia was considerably moderate in the E-PVP group. Finally, intranasal administration of IND emulsion with PVP may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects. Copyright © Informa Healthcare USA, Inc