The current study aimed to develop a prolonged-release pramipexole (PPX) transdermal patch for the treatment of Parkinson’s disease. Permeation parameters of PPX were investigated using human cadaver skin. Pramipexole patches were prepared using DURO-TAK® pressure-sensitive-adhesive (PSA) and evaluated for drug stability, drug loading, in vitro drug release, and in vitro permeation through mouse skin. The results indicated that blends of DURO-TAK® 87-2852 and DURO-TAK® 87-2510 were suitable for creating a prolonged-release PPX patch due to their advantages in drug release, drug loading, and stability. The final formulation consisted of 87-2852/87-2510 (70:30), 10% PG, and 15% PPX and showed a cumulative permeation amount of 1497.19 ± 102.90 μg/cm2 with a continuous flux over 6.0 μg/(cm2·h) across human cadaver skin for 7 days. In vivo studies in rats indicated that PPX patch produced a significantly longer (p < 0.001) half-life (t1/2, 75.16 ± 17.37 h) and mean residence time (MRT, 135.89 ± 24.12 h) relative to oral tablets (Sifrol®) and had a relative bioavailability of 51.64 ± 21.32%. Therefore, this study demonstrated the feasibility of developing a prolonged-release PPX patch, which proposed the potential to serve as an alternate to conventional oral tablets and may therefore improve patient compliance.

Based on the blend of styrene-isoprene-styrene (SIS) thermoplastic elastomer and acrylic resin Eudragit® EPO, amphiphilic hot-melt pressure sensitive adhesives (HMPSAs) were fabricated. Compatibility and micromorphology of SIS/EPO blends (SEBs) were analyzed with differential scanning calorimetry (DSC), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results showed that when the mass ratio of SIS to EPO was 1:1~1:2, bicontinuous structure was formed. Following the addition of an appropriate amount of polyethylene glycol (PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. Because of the compatibility between SIS and EPO, as well as the hydrogen bond interaction between EPO and PEG, amphiphilic HMPSAs showed good thermostability. The adhesive performance of HMPSAs was measured with 180° peeling strength and holding power. Geniposide and oleanolic acid were used as model drugs to investigate drug release behavior. When the mass ratio of PEG to SEB was 13:30~16:30, the HMPSAs could maintain good adhesion performance and achieve continual release of both hydrophilic and lipophilic drugs. In weakly acidic conditions, the HMPSAs exhibited good hygroscopicity and release profile, it was shown that pH sensitive amphiphilic HMPSAs were more suitable for transdermal drug delivery system (TDDS).

Poor permeability of stratum corneum limits the transportation of insulin across the skin. A transdermal peptide has exhibited enhancement activity on insulin transdermal delivery. A series of cationic cyclopeptides based on the sequence of TD-1 (ACSSSPSKHCG) were designed by the partial arginine or lysine scan method. Among these peptides, TD-34 (ACSSKKSKHCG) with bis-substituted lysine in N-5 and N-6 showed the best transdermal enhancement activity, with the blood glucose level lowered to about 26% of initial after administrating 2.1 IU insulin with 0.5 μmol of TD-34 in 100 μL of saline for 8 h to diabetic rats in vivo. In addition, the transmembrane permeability in Caco-2 cell monolayers (BL→AP) exhibited preferable correlation with percutaneous absorption of insulin (R2 = 0.73). It can be concluded that the appropriate content and position of cationic group in cyclopeptides may improve percutaneous absorption and transmembrane ability of insulin, and Caco-2 cell monolayers (BL→AP) might be applied to predict the percutaneous absorption of insulin chaperoned by a transdermal peptide in vivo.Keywords: insulin; Caco-2 cells; cyclopeptide; enhancement activity; transdermal;

A monomer-activated anionic polymerization approach was utilized to synthesize poly(styrene-b-isoprene-b-styrene-b-ethylene oxide) tetrablock terpolymers (SISO), which were melt-mixed with tackifiers and plasticizer to develop polar SISO-based hot-melt pressure-sensitive adhesives (HMPSAs) for transdermal delivery of hydrophilic drugs. Their hydrophilic performance was characterized using contact angle analysis. Their adhesive performances were measured in terms of 180° peel strength and holding power. In vitro drug release experiments were carried out using a modified Franz type horizontal diffusion cell, in which geniposide was chosen as a hydrophilic model drug. The results show that poly(ethylene oxide) (PEG) blocks exhibit substantial effects on adhesive performance and the release behavior of the model drug. The shorter PEG molecular chains enhance adhesive performance and the cumulative release rate of the model drug in the SISO-based HMPSAs. The longer PEG molecular chains tend to crystallize. Their crystallization structures have negative effects on adhesive performance and limit the dissolution and diffusion of drugs in the SISO-based HMPSAs. Therefore, appropriate PEG molecular chains are required to fabricate SISO-based HMPSAs with excellent adhesive performance for transdermal delivery of hydrophilic drugs.

BackgroundGlycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine.Hypothesis/PurposeThe aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics.Study design and MethodsGA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics.Results and conclusionIn dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48 h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy.Download high-res image (112KB)Download full-size image