Ampelopsin, one of the most common flavonoids, reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study was to enhance the dissolution rate and bioavailability of this drug by developing a novel delivery system that is microemulsion (ME) and to study the effect of microemulsion (ME) on the oral bioavailability of ampelopsin. Capmul MCM-based ME formulation with Cremophor EL as surfactant and Transcutol as cosurfactant was developed for oral delivery of ampelopsin. Optimised ME was evaluated for its transparency, viscosity, percentage assay and so forth. Solubilisation capacity of the ME system was also determined. The prepared ME was compared with the pure drug solution and commercially available tablet for
Ampelopsin, isolated from the tender stem and leaves of the plant species
Structure of ampelopsin.
Ampelopsin was obtained from Novopharm Formulations (Pvt. Ltd., Gujarat, India). Capmul MCM, Labrafac CC, Cremophor EL, Labrasol, and Transcutol P were obtained from Colorcon Asia (Mumbai). All other chemicals and reagents were of AR grade. Double-distilled water was used throughout the experiment.
ME formulations were prepared by the water titration method by varying the ratio of oil, surfactant, cosurfactant and water; keeping the concentration of Ampelopsin constant in each case (Table
Content in different ratio for selected microemulsion.
System | Oil | Surfactant | Cosurfactant | Water | Drug |
| |||||
ME-A | 1 | 1 | 1 | 3 | 1 |
ME-B | 3 | 6 | 3 | 10 | 1 |
M E-C | 5 | 10 | 2.5 | 20 | 1 |
The systems were visually inspected for homogeneity, optical clarity, and fluidity.
Transparency of both optimized ME formulation and its diluted forms (10 and 100 times with distilled water) was determined by measuring percentage transmittance through ultraviolet spectrophotometer (UV-1601-220x, Shimadzu). Percentage transmittance of samples was measured at 292 nm using purified water as blank.
Microemulsions were subjected to examination under cross-polarizing microscope for the absence of birefringence to exclude liquid crystalline systems.
The rheological behaviour of ME (0.5 mL) was evaluated using Brookfield LVDV and CP Viscometer (Brookfield, USA) by means of rheological software. Both rheometers were equipped with automatic gap setting. A 5 cm, 18 cone (CP-40), and plate geometry with a solvent trap was used to all investigated samples, and the temperature in the measuring geometry was controlled to within
Electrical conductivity of ME was measured using a conductometer [(CM 180 conductivity meter (Elico, India))]. Calibration was done using freshly prepared standard KCl solutions. To ensure efficient phase separation of excess water, samples at
The loading efficiency of drug in each formulation was determined spectrophotometrically at 292 nm, 5 mL of ME formulation was diluted upto 25 mL with acetonitrile and centrifuged at 4000 rpm at
The solubility data of Ampelopsin in various vehicles are provided in Table
Solubility studies in various vehicles.
Vehicles | Solubility [(mg/mL) ± standard deviation (SD)] |
| |
Capmul MCM |
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Labrafac CC |
|
Cremophor EL |
|
PEG 600 |
|
Transcutol P |
|
Optimised ME |
|
Content of optimized formulation ME-C.
System | Oil | Surfactant | Cosurfactant | Water | Drug |
| |||||
ME-C | 5 | 10 | 2.5 | 20 | 1 |
Percentage transmittance of ME after 10 times and 100 times dilution was 98.39% and 98.12%, respectively; indicating transparency and stability of optimized ME.
Examination under cross-polarizing microscope showed dark field indicating no change in isotropic character, and no crystals of the drug were detected, indicating that the drug was completely dissolved and has optical isotropy property.
Drug content in the optimized ME formulation was found to be 98.11%.
The structure and type of ME system was characterized by rheological measurements. Results obtained from the viscosity study reveal that viscosity increased from 50.31 cP to 75.42 cP, with increasing water content which then gradually decreased (Figure
Viscosity changes of ME with increasing water content.
Results indicated that electrical conductivity increased rapidly up to 59.54% of the aqueous phase addition. Therefore, it was not affected significantly with further addition of the aqueous phase (Figure
Results of the electroconductivity study.
Results of the
Physicochemical characterization showed that the system undergoes a structural transition from water-in-oil to bicontinuous microemulsion system upon addition of water. The conductivity and viscosity studies provided evidence for the structural transition from water-in-oil to bicontinuous phases. ME-C was found to be the best for use as a drug delivery system on the basis of its optimal solubility for Ampelopsin. After the incorporation of the drug, the microemulsion systems remained stable and optically clear showing no phase separation. The solubility of the drug was confirmed using conductivity measurements which indicated that the drug may be present at the interface of the oil and aqueous phases. UV-visible spectroscopic studies indicated that the system was optically clear. We can conclude that our microemulsion system helps increase the solubility of the hydrophobic drug with the help of hydrophobic component of microemulsion and lipophilic part of the surfactant. The developed ME, containing Capmul MCM (5.5%), Cremophor EL (25%), Transcutol P (8.5%), and distilled water, was found to be a transparent fluid. ME showed higher