| Vancomycin hydrochloride,a first-generation glycopeptide antibiotic,was discovered in the 1950s and is primarily employed for the treatment of infections caused by Methicillinresistant Staphylococcus aureus(MRSA).This antibiotic is typically deployed as a last-line drug when other antibiotics prove ineffective.However,due to the current limitations in the diversity of dosage forms and some associated drawbacks in its formulation,the clinical applications of vancomycin hydrochloride are restricted.To address this issue,our research project focused on formulating vancomycin hydrochloride into a transdermal patch using physical permeation enhancement technology(a combination of microneedle-electroporation),and studied the preparation process and the pharmacokinetics of the resulting patch.In our study on parameter optimization for the microneedle-electroporation permeation enhancement method,we identified the factors that have the greatest influence on the cumulative permeation and transdermal absorption efficiency of vancomycin hydrochloride.These factors included pulse voltage and pulse duration for electroporation,and microneedle length and the number of rolls for the microneedles.Following the examination of each of these individual factors,we conducted a four-factor,three-level orthogonal experiment to optimize them.Consequently,we established that the optimal experimental parameters for the microneedle-electroporation were a pulse voltage of 100 V,a pulse duration of 100 ms,a microneedle length of 0.5 mm,and a rolling count of 5 times.Notably,our experiments demonstrated a significant increase in the transdermal permeation of the drug under these parameters,indicating that these conditions are both stable and feasible.As part of our investigation into the prescription and preparation process of the vancomycin hydrochloride transdermal patch,we used the appearance,adhesiveness,and cumulative permeation of the patch as evaluation indicators.We conducted a four-factor,threelevel orthogonal experiment to optimize the prescription and preparation process after investigating single factors such as the amount of pressure-sensitive adhesive,types and amounts of plasticizers,types and amounts of permeation enhancers,and drug loading.As a result,the optimal preparation process was found to be 1.5 g of pressure-sensitive adhesive(Eudragit L100),1.0 g of polyvinylpyrrolidone(K-30),8%menthol,and 1%drug loading.This preparation process was deemed simple,easy to operate,and stable.In the quality evaluation of the vancomycin hydrochloride transdermal patch,our selfmade patch’s appearance,adhesiveness,and weight variation were all found to comply with the relevant provisions of the 2020 edition of the Chinese Pharmacopoeia.All three batches of patches were of a milky white color with uniformity,a uniform matrix with no paste separation,and a smooth,intact surface with no bubbles.In the initial adhesion experiment,all three batches of patches were able to adhere to a No.10 steel ball,with a residence time on the patch surface exceeding 7 seconds.The sustained adhesion experiment revealed a relatively close drop-off time of the adhesion strength of the three batches of patches,with an average drop-off time between 67.00 and 72.00 minutes.In terms of peel strength,the three batches had a similar drop-off time,averaging 5.82±2.65 minutes,with a peel strength range of 3.20±2.17 N/cm.Examination of weight variations demonstrated that the weight difference across 20 transdermal patches was less than 5%,with no single patch exceeding the weight difference limit by a factor of one.Tests of cumulative penetration showed a gradual and relatively stable increase within 0-8 hours across the three batches,with the cumulative penetration amount at 8 hours being roughly equivalent,at 152.23±5.01 μg/cm2,152.64±3.12 μg/cm2,and 148.78±3.11μg/cm2,respectively.This uniformity ensures that the drug can effectively diffuse and be absorbed within the body.The in vitro release rate for each of the three batches reached over 70%within 12 hours,with content determination results averaging 32.97±1.81 mg/patch.In a pharmacokinetic study of Vancomycin Hydrochloride transdermal patches in rats,it was found that after administration of the transdermal patches,aided by the combined effects of microneedles and electroporation,Vancomycin Hydrochloride was able to reach a maximum absorption concentration(Cmax)of 3.66 μg/mL within 10 hours.The area under the blood drug concentration-time curve(AUC(0-48))was 85.507 μg/mL×h,the mean residence time(MRT(0-48))was 17.311 hours,the half-life(T1/2)was 11.263 hours,and F was 52.81%.Our preliminary research indicates that the incorporation of microneedles and electroporation can effectively enhance the drug’s permeation amount,maintain a relatively steady blood drug concentration,extend the drug’s treatment duration compared to intravenous injection,reduce the frequency of administration,and thereby improving patient compliance. |
