Hybrid Dissolving Microneedle-Mediated Delivery of Ibuprofen: Solubilization, Fabrication, and Characterization

Abstract

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg).

Transdermal Delivery of Glimepiride: A Novel Approach Using Nanomicelle-Embedded Microneedles

“…The pharmacokinetic parameters were determined for various groups of volunteers after three dissolving MN patches were applied to the wrist (volar part) as shown in Figure 19 via a spring applicator with 1.6 N force and secured with medical tape for 48 h. The zero-order model was found to be the best fit for the drug release in both nanomicelles and DMNs (R 2 = 0.9916 and 0.905), suggesting that the dissolution of glimepiride from the PVP K-90: PVA patch and GM nanomicelles is concentration-independent, which is the most desirable pattern [67] as depicted in Figure 18. Hixon-Crowell model was the best fit for the release data with the R 2 of 0.9871 and 0.8603 for nanomicelles and nanomicelle-loaded MNs, respectively [28]. The results indicated that the GM from the GM nanomicelles and nanomicelle-loaded MNs is released via dissolution of the polymeric matrix; this is in agreement with the drug release from Soluplus ® nanomicelles and the PVP K-90 matrix reported earlier [29,68].…”

“…Hixon–Crowell model was the best fit for the release data with the R 2 of 0.9871 and 0.8603 for nanomicelles and nanomicelle-loaded MNs, respectively [ 28 ]. The results indicated that the GM from the GM nanomicelles and nanomicelle-loaded MNs is released via dissolution of the polymeric matrix; this is in agreement with the drug release from Soluplus ® nanomicelles and the PVP K-90 matrix reported earlier [ 29 , 68 ].…”

“…The effect of different concentrations of Soluplus ® ( n = 3), i.e., 1%, 2%, 4%, 6%, 8%, and 10% w / v , were tested to achieve maximum solubility and to optimize the Soluplus ® concentration as reported earlier [ 28 , 29 ]. An excess amount of drug was gradually added to each 5 mL different concentration of Soluplus ® aqueous dispersion to create saturated micelles [ 30 ].…”

“…The drug–polymer blend (GM: PVP K-90: PVA) in a 1:1 was incorporated into the microarray mold [ 25 , 36 ] applying a vacuum of −90 kPa for about 6 min at room temperature using an oil-less vacuum pump to ensure optimal filling [ 37 ]. A drug-free backing layer of PVP K-90 and PVA was then added to the mold and subjected to vacuum under the same conditions [ 28 ]. The array was left to dry for 24 h at room temperature [ 38 ] and were manually detached from molds with an adhesive tape and stored in a control conditions of temperature and humidity [ 25 ].…”

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs

“…In addition, anti-inflammatory activity was found to be significantly increased following treatment with microneedle systems compared to systems without microneedles [115]. Microneedle arrays have also been used to enhance the transdermal permeation of other NSAIDs, such as diclofenac [116,117], ibuprofen [118,119], and acetaminophen [116].…”