Brinzolamide-Loaded Nanoemulsions: In vitro Release Evaluation

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel ophthalmic delivery systems for brinzolamide (BZD). Phase behavior of quaternary systems composed of triacetin and CapryolTM 90 (selected oils, screened through the solubility studies), various surfactants (namely, Cremophor RH 40, Brij 35, Labrasol and tyloxapol), Transcutol P (as co-surfactant) and water at different surfactant/co-surfactant weight ratios (Rsm) was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region on the phase diagrams, depending on the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 0.4 wt% of the drug. The nanosized character of NEs was evaluated, the cumulative drug release from of the selected formulations was determined for a period of 6 h, using a dialysis sac technique and the release efficiency for NEs was calculated. The therapeutic efficacy of the selected BZD-loaded NEs to lower the IOP was assessed by the calculation of various pharmacodynamic parameters (ie., Emax, Tmax AUC0-6h). In all cases, the average size of the droplets was found to be less than 40 nm. In vitro release studies indicated that the release efficiency in most of the NEs was higher as compared to the BZD ophthalmic suspension. Comparison of the pharmacodynamics parameters confirmed the equivalent efficacy of most BZD formulations

Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods

In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs) with phospholipid-polyethylene glycols (Pl-PEGs) was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations) was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution

An Investigation into the Effect of Various Penetration Enhancers on Percutaneous Absorption of Piroxicam

Abstract Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermatological products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to evaluate the effect of incorporating a few common penetration enhancers (in different concentrations) into a 0.5% w/w piroxicam (model drug) gel formulation, on the permeability rate of drug through rat abdominal skin in vitro. For this purpose various concentrations of oleic acid (OA), urea (UR), lecithin (LEC) and isopropyl myristate (IPM) were used as the penetration enhancer. In order to investigate the effect of penetration enhancers used in this study on the permeability rate of piroxicam through sections of excised rat skin, Franz-type diffusion cells were employed. The receptor phase was constantly stirring 0.9% w/v sodium chloride solution at 32°C. At set intervals up to 8h, 5ml samples were removed from the receptor compartment and the amount of piroxicam permeated through the skin calculated by determining the UV absorbance of drug at 353 nm. Results show that among the penetration enhancers used, the use of OA at a concentration of 1.0% w/w had the greatest effect on the permeability rate of piroxicam, and produced the highest enhancement ratio among all the penetration enhancers examined. The other penetration enhancers used were found to have a far smaller effect on the permeability rate of piroxicam through rat skin. The enhancement ratio of the penetration enhancers used in the formulation of piroxicam gel were found to increase in the order of OA>> IPM > LEC > UR

Rapamycin-loaded, capryol� 90 and oleic acid mediated nanoemulsions: Formulation development, characterization and toxicity assessment

This study was planned to explore the capability of nanoemulsions (NEs) consisting of Capryol� 90 and oleic acid for the delivery of rapamycin (RAP). Permeability and cytotoxicity of RAP-loaded NEs were also inspected. Pseudo-ternary phase diagrams were created with oleic acid and Capryol� 90 (as oil phase) and four surfactants and co-surfactants at various weight ratios (Rsm). Selected NEs from O/W region on the phase diagrams with the drug concentration of 1 mg/mL, were prepared via the spontaneous emulsification technique, characterized for particle size and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release was determined for a period of 48 h using a dialysis sac. The assay of RAP was determined using HPLC technique. Cytotoxicity of NEs was evaluated by MTT assay on breast cancer cell line, namely SKBR-3. The permeability of RAP-loaded NEs across Caco-2 monolayers was assessed by measurement of TEER (transepithelial electrical resistance) value. The intracellular uptake of coumarin 6-loaded NEs by SKBR-3 cells was also investigated using florescence microscopy. NEs containing oleic acid/Tween 20/propylene glycol, Capryol� 90/Tween 20/iso-propanol, and Capryol� 90/Cremophor® RH40/Transcutol® P showed more cytotoxicity and permeability compared with the RAP methanolic solution. The minimum toxic concentration of RAP in NE formulations was found to be 7.5 µg/mL. The highest intracellular uptake was observed for the NE composed of Capryol� 90/Tween 20/iso-propanol which was in consistent with the results obtained from cytotoxicity and permeability tests. The overall results implicated that this novel carrier was effective for enhancing RAP permeation in Caco-2 cell membrane along with enhancement of cytotoxicity. © 2018, Iranian Journal of Pharmaceutical Research. All rights reserved

Biodynamic parameters of micellar diminazene in sheep erythrocytes and blood plasma

In this work, we used a preparation of diminazene, which belongs to the group of aromatic diamidines. This compound acts on the causative agents of blood protozoan diseases produced by both flagellated protozoa (Trypanosoma) and members of the class Piroplasmida (Babesia, Theileria, and Cytauxzoon) in various domestic and wild animals, and it is widely used in veterinary medicine. We examined the behavior of water-disperse diminazene (immobilized in Tween 80 micelles) at the cellular and organismal levels. We assessed the interaction of an aqueous and a water-disperse preparation with cells of the reticuloendothelial system. We compared the kinetic parameters of aqueous and water-disperse diminazene in sheep erythrocytes and plasma. The therapeutic properties of these two preparations were also compared. We found that the surface-active substances improved intracellular penetration of the active substance through interaction with the cell membrane. In sheep blood erythrocytes, micellar diminazene accumulated more than its aqueous analog. This form was also more effective therapeutically than the aqueous analog. Our findings demonstrate that use of micellar diminazene allows the injection dose to be reduced by 30%