sorbitan-monooleate and carbitol

Thiocolchicoside (TCC) is an effective therapeutic agent against the orthopaedic, traumatic and rheumatologic disorders but it suffer from the drawback of poor bioavailability due to extensive first pass metabolism and low permeability via the oral route. The aim of the present study was to evaluate the potential of nanoemulsion (NE) for bioavailability enhancement of TCC through the transdermal route. The NEs were developed using Linseed: sefsol in 1:1 ratio as the oil phase, span 80, Transcutol P and distilled water as surfactant, co-surfactant and aqueous phase. Furthermore, selected formulations were subjected to physical stability and consequently evaluated for in vitro permeation using porcine skin. The optimized formulation had small average globule diameter of 117 nm with polydispersity index of 0.285. The globules were spherical in shape as observed by transmission electron microscopy. The in vitro skin permeation profile of optimized NE was compared with aqueous solution of TCC. Significant increase in permeability parameters were observed in NEs formulation (p < 0.05) as compared to aqueous solution of TCC. The steady-state flux (Jss) and permeability coefficient (Kp) for optimized NE formulation (C1) were found to be 30.63 ± 4.18 µg/cm(2)/h and 15.21 × 10(-3) ± 2.81cm(2)/h, respectively. The results of enhanced permeation through transdermal route suggest that water-in-oil NEs which are compatible with the lipophilic sebum environment of the hair follicle facilitate the transport of TCC, and such transport might be predominantly transfollicular in nature. Overall, these results suggested that water-in-oil NEs are good carriers for transdermal delivery of TCC.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Calorimetry, Differential Scanning; Colchicine; Drug Carriers; Drug Compounding; Drug Stability; Emulsions; Ethylene Glycols; Hexoses; Hydrogen-Ion Concentration; In Vitro Techniques; Kinetics; Linseed Oil; Microscopy, Confocal; Microscopy, Electron, Transmission; Nanoparticles; Nanotechnology; Permeability; Polymers; Propylene Glycols; Skin; Skin Absorption; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; Surface-Active Agents; Swine; Technology, Pharmaceutical; Viscosity; Water

This project was carried out to exploit the feasibility of using microemulsion (ME) as an alternative carrier for percutaneous delivery econazole nitrate (ECN) and elucidate the underlying mechanism of permeation enhancement. The ME was developed based on Labrafil M 1944 Cs as oil phase, Solutol HS15 and Span 80 as surfactants, Transcutol P as cosurfactant and water as aqueous phase. The solubility of ECN was firstly determined for screening the ingredients of the system. Pseudo-ternary phase diagrams were constructed to formulate ME and select surfactant and cosurfactant. Central composite design-response surface methodology (CCD-RSM) was utilized to optimize the formulation of ME. The ECN loaded ME was characterized in terms of morphology, particle size and size distribution, pH value, refractive index, viscosity and conductivity, and storage stability of the ECN loaded ME was assayed. Percutaneous permeation of ECN from ME in vitro through rat skin was investigated in comparison with PBS aqueous suspension (1%, w/w), and results showed that ME enhanced drug retention in the skin and permeation through the skin, the enhancement of ME on skin deposition was further visualized through fluorescent-labeled ME by confocal laser scanning microscope (CLSM). The action mechanism of ME on improving percutaneous delivery was studied by performing a pretreatment test. It can speculate that ME does not simply behave as enhancer but it also acts as drug carrier. Furthermore, ME-skin interaction was elucidated through transmission electron microscope (TEM), and attenuated total reflectance fourier-transform infrared (ATR-FTIR). TEM was performed to visualize the micro morphological change of skin. ATR-FTIR was carried out to investigate the molecular vibrations of the components of stratum corneum (SC). The results indicate that the ME system may be a promising vehicle for percutaneous delivery of ECN.

Topics: Administration, Cutaneous; Animals; Antifungal Agents; Drug Carriers; Econazole; Emulsions; Ethylene Glycols; Feasibility Studies; Female; Glycerides; Hexoses; Microscopy, Confocal; Microscopy, Electron, Transmission; Particle Size; Permeability; Polyethylene Glycols; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Spectroscopy, Fourier Transform Infrared; Stearic Acids; Surface-Active Agents; Technology, Pharmaceutical; Water

Microemulsions show significant promise for enhancing the oral bioavailability of biopharmaceutics classification system (BCS) class II drugs, but how about class III drugs remains unclear. Here we employed metformin hydrochloride (MET) as the model drug and prepared drug-loaded water-in-oil (W/O) microemulsions selecting different hydrophile-lipophile balance (HLB) surfactant systems, using HLB 8 as a cut-off. We examined the phase behaviors of microemulsions after dilution and attempted to correlate these behaviors to drug oral bioavailability. ME-A, including a lower content of surfactants (35%), underwent a transition of W/O emulsion and then became a stable O/W emulsion in a light milky appearance; ME-B, in contrast, introducing a higher content of surfactants (45%), still remained transparent or semitransparent upon dilution. Unexpectedly, ME-A showed significantly higher oral bioavailability, which can be reduced by blocking the lymphatic absorption pathway. Comparatively, the AUC of ME-B is lower, close to MET solution. Both microemulsions behaved similarly in intestinal perfusion test because of the dilution before perfusion, lacking of the important phase transition of W/O emulsion. These findings suggest that W/O microemulsions improve oral bioavailability of BCS class III drug by promoting lymphatic absorption. Analyzing the phase behavior of microemulsions after dilution may help predict the drug oral bioavailability and optimize formulations.

Topics: Administration, Oral; Animals; Biological Availability; Emulsions; Ethylene Glycols; Glycerides; Glycerol; Hexoses; Hypoglycemic Agents; Intestinal Absorption; Intestinal Mucosa; Linoleic Acids; Male; Metformin; Oleic Acids; Organic Chemicals; Phase Transition; Polysorbates; Rats, Sprague-Dawley; Solubility; Surface-Active Agents; Water