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Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC. Refereed/Peer-reviewed

The aim of the present study was to find a way of prepare silybin-phospholipid complex to make oral bioavailability of silybin increase and to study its physicochemical properties and to compare the pharmacokinetic characteristics and bioavailability after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine in rats. Using ethanol as a reaction medium, silybin and phospholipids were resolved into the medium, after the organic solvent was removed under vacuum condition, silybin-phospholipid complex was formed. The new complex's physicochemical properties including scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), solubility, dissolution, etc., were tested. The concentrations of silybin after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine at different time in rats were determined by RP-HPLC. The pharmacokinetic parameters were computed by software program 3p97. Our data showed that silybin and phospholipids in the silybin-phospholipid complex were combined by non-covalent-bond, not forming a new compound and the solubility of silybin-phospholipid complex in water and in n-octanol was effectively enhanced. We found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex and silybin-N-methylglucamine in rats was both in accordance with open single-compartment model with first-order absorption. Pharmacokinetic parameters of silybin in rats were Tmax 10 and 5 min; Cmax 126.72 and 104.29 ng ml(-1); AUC(0-infinity) 1020.33 and 235.81 ng ml(-1)h, respectively. The bioavailability of silybin in rats was increased remarkably after oral administration of silybin-phospholipid complex comparing to silybin-N-methylglucamine. This was mainly due to an impressive improvement of the lipophilic property of silybin-phospholipid complex and improvement of the biological effect of silybin.

Aim To compare pharmacokinetics of intravenous breviscapine liposomes in Beagle dogs, rabbits and rats. Methods Six Beagle dogs, 6 rabbits and 12 rats were intravenously administrated with breviscapine liposomes and commercial injection (breviscapine solution) by the crossover design (two periods), respectively. Plasma concentration of scutellarin, the main active component in breviscapine, at different time intervals was determined by reverse phase-HPLC. The pharmacokinetic parameters including area under the curve (AUC), clearance (CL (s) ) and volume of distribution ( V (c) ) were calculated. Results The plasma concentration–time profiles were fitted to a two-compartment model. Breviscapine liposomes exhibited significant difference from injection in CL (s) and AUC, examined by a one-way analysis of variance (ANOVA). With regard to both breviscapine liposomes and commercial injection (free breviscapine), the logarithm values of AUC, CL (s) and V (c) were all related to the logarithm of the body weight by the allometric equation: Y = a × W b . Conclusion The allometric equation might be applied to extroplate dosage for human from animal data and also for dosage adjustment of breviscapine liposomes in order to achieve same AUC as commercial injection. Compared with the breviscapine solution, breviscapine liposomes delivered more scutellarin into the plasma.