Preparation, in-vitro evaluation and pharmacodynamic study of minoxidil topical nanoemulsionbased gel

Androgenetic alopecia is a common type of hair loss and a very common
dermatological disorder. Minoxidil is a potent vasodilator that has been
approved by the FDA as a topical solution or foam for the treatment of
androgenetic alopecia. However, the delivery of minoxidil from conventional
topical solutions suffered from short contact time with the scalp, poor drug
penetration, and high dose requirements
This work aims to prepare an o/w nanoemulsion-based gel of minoxidil to
prolong contact time with the scalp and possible enhanced pharmaco-dynamic
effects.
Preliminary studies were conducted to make a suitable selection of oil
phase, surfactant and surfactant/co-surfactant ratios. Eight formulae of
minoxidil loaded nanoemulsion were prepared and subjected to different
investigational studies such as measurement of pH, electrical conductivity,
percent of light transmittance, drug content and entrapment efficiency, droplet
size, polydispersity, zeta potential, and thermodynamic stability studies to
determine the optimum formula. Then, the selected formula is subjected to
further studies such as in-vitro drug release, transmission electron microscopy
and pharmaco-dynamics studies.

Moreover, in the second part of the study, three different minoxidil-loaded
nanoemulgel formulae were prepared by using the selected formula of
nanoemulsion with three different concentrations of carbopol 934. The
prepared nanoemulgel formulae were further subjected to characterization
studies such as drug-excipient compatibility study by Fourier Transform
Infrared Spectroscopy (FTIR), measurement of pH, spreadability, viscosity, invitro drug release, permeation studies and stability study under different storage
conditions to determine the best minoxidil-loaded nanoemulgel formula.

The results of characterization showed that the minoxidil loaded
nanoemulsion NE-A2 formula with Smix ratio (2:1), 5% oil concentration, and
40% Smix concentration was the optimized formula (hydrodynamic diameter
of 14.62 ±1.36 nm, PDI of 0.22 ±0.021, Zeta potential of - 4.7 ±0.6 mV and
entrapment efficiency of 91.2 ±0.31%). The results of The EM of the selected
formula showed spherical droplets that appeared to be less than 100 nm. The
pharmaco-dynamic study showed that the average relaxation percentage for
optimized nanoemulsion formula NE-A2 was equal to 76.73 ±7.490% while
that for the marketed solution was 14.59 ±1.233%.
The characterization results of the optimized minoxidil-loaded
nanoemulgel formula NEG-A2y demonstrated that the formula has an
acceptable pH value with optimum spreadability (21.6 ±0.70 g.cm/s), and
optimum viscosity (492 ±87.81 cp) for nanoemulgel to be applied topically.
The in-vitro release profile of the optimized minoxidil-loaded nanoemulsion
formula NE-A2 has a higher release than that of standard solution and marketed
solution at 420 minutes, and it was noticed that the cumulative release profile
of optimized minoxidil-loaded nanoemulgel formula NEG-A2y is slower than
that of alcoholic standard solution and marketed solution. Based on the
permeation study results, the optimized nanoemulgel formula NEG-A2y
exhibited a better permeation profile than the marketed solution and the
cumulative amount of MXD that permeated through the skin over 24 hours
from the NEG-A2y formula was 961.97 ±4.77 µg/cm2
, which is significantly
(P≤0.05) higher than that from the marketed solution, 398.24 ±10.03 µg/cm2
.
The nanoemulgel formula NEG-A2y was checked for stability, and it was
shown that the formula is stable at different temperatures.