Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide (A771726)

Abstract

Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying antirheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The results of antiinflammatory effect showed that compared with the control group, the external TEF microemulsion group could significantly inhibit swelling of paw in rats, and no significant difference compared with oral LEF group. The results of hepatotoxicity test show that there were normal content of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and no obvious inflammatory infiltration of TEF microemulsion group compared with LEF group. The plasma concentration curve showed that compared with LEF group, the peak concentration of TEF microemulsion group was decreased, the half-life (t 1/2) was prolonged, and the relative bioavailability of TEF microemulsion was 75.35%. These results suggest that TEF W/O microemulsion can be used as a promising preparation to play an anti-inflammatory role while significantly reducing hepatotoxicity.

Quality by Design (QbD) Approach for Optimization and Characterization of Micro emulsion based Nasal formulation of Antipsychotic/Antischizophrenic Drug-Aripiprazole

“…[10][11][12] Polynomial model was constructed for optimization of Aripiprazole keeping four independent and two dependent variables [ Table 2 which will surely helpful in stable micro emulsion development. [10][11][12][13][14] Pharmaceutical evaluation of Micro emulsion Optical clarity (Percentage transmittance): Percentage transmittance of each formulation was measured at 650 nm using UV-spectrophotometer against distilled water as blank. 9,15 Percentage transmittance indicates the homogenous nature and clarity of formulation.…”

“…16,17 Viscosity: Viscosity of the formulations were determined using Brookfield cone and plate Rheometer using CPE spindle at the rotational speed of 5rpm, shear rate of 10 at 33.8±0.3°C. 14,15 pH measurement: The excipients used in the formulation decide the pH of the final preparation. pH is also responsible for stability of micro emulsion.…”

“…16 Refractive Index: The refractive index of the system was measured by a simple Abbe's refractometer by placing 1 drop of AME on the slide. 14,15 Drug content Estimation: Micro emulsion equivalent to 15 mg of Aripiprazole was dissolved in suitable quantity of ethanol (100 ml).…”

“…The samples were mixed thoroughly to dissolve the drug in ethanol and percentage drug content analysed using Shimadzu UV visible spectrophotometer at 255 nm. [12][13][14] Biological Evaluation: Freshly excised sheep nasal mucosa without septum part was obtained from the slaughter house. This membrane was kept in PBS at pH 6.4 for 15 min to equilibrate.…”

Microemulsion assisted transdermal delivery of a hydrophilic anti-osteoporotic drug: Formulation, in vivo pharmacokinetic studies, in vitro cell osteogenic activity

“…Low electrical conductivity is a typical property of w/o microemulsion due to the presence of a non-aqueous outer phase. As electrical conductive component in a microemulsion is water, it is present as the inner phase, and the low electrical conductivity is observed when w/o microemulsions are concerned (Cao et al, 2019;Kantaria et al, 2003). The conductivity of both, blank and drug-containing w/o microemulsion, was found to be quite low (Table 2).…”