A new topical transdermal sildenafil gel formulation to improve skin flap viability in a rabbit model
Skin flap survival is one of the most important outcomes in reconstructive surgery. Various applications of pharmacological agents with different dosing regimens have been shown to improve flap survival experimentally with varying degrees. This study aimed to produce an effective topical gel form...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://eprints.usm.my/46077/1/Dr.%20Kho%20Swee%20Liang-24%20pages.pdf |
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| Summary: | Skin flap survival is one of the most important outcomes in reconstructive
surgery. Various applications of pharmacological agents with different dosing
regimens have been shown to improve flap survival experimentally with varying
degrees. This study aimed to produce an effective topical gel formulation of
sildenafil citrate for the improvement of skin flap survival. Characterization of
physicochemical properties and basic stability tests were carried out on the gel
formulation. Skin flaps (14 cm x 5 cm) based on superficial inferior epigastric
vessels was designed and raised on nine New Zealand White rabbits (weight range
2.5-3.2 kg). An aliquot of 1 ml gel consisted of sildenafil citrate (3 mg) was applied
immediately post-surgery to the distal half of the flap in treatment group (n = 3)
while 1 ml gel without sildenafil was applied to vehicle control group (n = 3), and
none was applied to controls (n = 3). Blood perfusion at the flap distal end and mean
necrotic index of the skin flaps were measured continually for 10 days after the flap
surgery using laser Doppler flowmetry (LDF) and 2-plane planimetry, respectively.
Necrotic index (mean ± standard deviation) in the treatment group was significantly
lower compared to control and vehicle control group (Treatment group, 0.25 ±
0.43% vs. vehicle control 5.41 ± 3.50% vs. control 5.41 ± 1.53%; p = 0.017). Early
blood perfusion improvement was observed in the treatment group with significant
increase seen at flap distal end on the first 24 hours post-surgery (p < 0.001). Ex
vivo drug release data of the sildenafil gel across rabbit skin (n = 3) showed that
more than half of the drug content were released after six hours (58.03%) and
95.84% of the drug were released after 24 hours. The drug release in the first 24
hours was found to follow the first-order kinetic model, and the release exponent, n,
was found to be greater than 1.0 using the Korsmeyer-Peppas equation. Both kinetic
analyses showed that the current sildenafil gel formulation demonstrated controlled
release properties for extended drug release. In conclusion, this study demonstrated
that single application of the current gel formulation of sildenafil (3 mg/ml)
significantly increased microcirculatory blood perfusion at the flap distal end and
improved skin flap survival in rabbits. |
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