title: Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution.
abstract: The dissolving microneedle array (DMNA) offers a novel potential approach for transdermal delivery of biological macromolecular drugs and vaccines, because it can be as efficient as hypodermic injection and as safe and patient compliant as conventional transdermal delivery. However, effective needle drug distribution is the main challenge for clinical application of DMNA. This study focused on the mechanism and control of drug diffusion inside DMNA during the fabrication process in order to improve the drug delivery efficiency. The needle drug loading proportion (NDP) in DMNAs was measured to determine the influences of drug concentration gradient, needle drying step, excipients, and solvent of the base solution on drug diffusion and distribution. The results showed that the evaporation of base solvent was the key factor determining NDP. Slow evaporation of water from the base led to gradual increase of viscosity, and an approximate drug concentration equilibrium was built between the needle and base portions, resulting in NDP as low as about 6%. When highly volatile ethanol was used as the base solvent, the viscosity in the base rose quickly, resulting in NDP more than 90%. Ethanol as base solvent did not impact the insertion capability of DMNAs, but greatly increased the in vitro drug release and transdermal delivery from DMNAs. Furthermore, the drug diffusion process during DMNA fabrication was thoroughly investigated for the first time, and the outcomes can be applied to most two-step molding processes and optimization of the DMNA fabrication.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Department of Pharmacy, Bengbu Medical College, Bengbu, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Gangtao
authors.initials: G
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Dong
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Guangzhou Neworld Co. Ltd., Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; GuangDong Research Center for Drug Delivery Systems, Guangzhou, China. Electronic address: chuanbin_wu@126.com.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry; D001672:Biocompatible Materials; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004356:Drug Storage; D004867:Equipment Design; D008790:Metoprolol / Q000737:chemistry; D009339:Needles; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D001672:Biocompatible Materials; D012710:Serum Albumin, Bovine; D008790:Metoprolol
keywords: Dissolving microneedle array (DMNA); Drug diffusion; Drug distribution; Solvent evaporation; Transdermal drug delivery; Two-step molding