Abstract��OBJECTIVE To prepare dissolving microneedles using Gantrez S-97 and PVPk30 as composite matrix materials to accelerate the delivery of poorly water soluble drugs and study the preparation, appearance, mechanical properties, intradermal solubility, drug efficacy and crystallization behavior of dissolving microneedles. METHODS Using polydimethylsiloxane(PDMS) as the negative mode, microneedles were prepared by the reverse casting method. SEM was used to observe the morphological appearance of the microneedles. The mechanical properties of the microneedles were investigated by texture analyzer and histological sections. Delivery of lidocaine was characterized by intradermal dissolution and pharmacodynamics. Crystallization behavior of lidocaine was characterized by DSC. RESULTS Lidocaine dissolving microneedles had good needle shape and possessed sufficient mechanical strength to penetrate into the skin. The microneedles could dissolve in the dermis within 3 min and retain anesthetic effect, and the drug existed in amorphous form in the microneedles. CONCLUSION Cosolvent preparation of dissolving microneedles has potential for promoting the delivery of poorly water soluble drugs.
HENRY S, MCALLISTER D V, ALLEN M G, et al.Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci,1998,87(8):922-925.
LEE D S, LI C G, IHM C, et al. A three-dimensional and bevel-angled ultrahigh aspect ratio microneedle for minimally invasive and painless blood sampling. Sens Actuators B Chem, 2018, 255:384-390.
HWA K Y, CHANG V H S, CHENG Y Y, et al. Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery. Biomed Microdev, 2017, 19(4):84.
HUANG Y C, MA F S, ZHAN H H. Microneedle array used for transdermal delivery of biomacromolecules. Pro Biochem Biophys(���ﻯѧ�����������չ), 2017, 44(9):757-768.
HIROBE S, OTSUKA R, IIOKA H, et al. Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo. Life Sci, 2017, 168:24-27.
YAO G, QUAN G, LIN S, et al. Novel dissolving microneedles for enhanced transdermal delivery of levonorgestrel:in vitro and in vivo characterization. Int J Pharm, 2017, 534(1-2):378-386.
GRIFFIN P, ELLIOTT S, KRAUER K, et al. Safety, acceptability and tolerability of uncoated and excipient-coated high density silicon micro-projection array patches in human subjects. Vaccine, 2017, 35(48):6676-6684.
MA S, XIA Y, WANG Y, et al. Fabrication and characterization of a tungsten microneedle array based on deep reactive ion etching technology. J Vac Sci Technol B Nanotechnol Microelectron, 2016, 34(5):052002.
WENDORF J R, GHARTEY-TAGOE E B, WILLIAMS S C, et al. Transdermal delivery of macromolecules using solid-state biodegradable microstructures. Pharm Res, 2011, 28(1):22-30.
BERGSTRÖM C A S, LUTHMAN K, ARTURSSON P. Accuracy of calculated pH-dependent aqueous drug solubility. Eur J Pharm Sci, 2004, 22(5):387-398.
LEE U, CHOI Y J, CHOI G J, et al. Intravenous lidocaine for effective pain relief after bimaxillary surgery. Clin Oral Investig, 2017,21(9):1-8.
ZHOU W, LIU C, LU M J. The impact of filling endotracheal tube cuff with lidocaine carbonate on postoperative sore throat in general anaesthesia. J Clin Anesthesiol(�ٴ�����ѧ��־), 2013, 29(11):1051-1053.
ZHONG C, WANG L P. Preemptive analgesia of lidocaine-prilocaine cream on hypertrophic scars injection with low pressure needle free syringe. Chin J Nurs(�л�������־), 2017, 52(2):190-192.
KREILGAARD M, KEMME M J B, BURGGRAAF J, et al. Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics. Pharm Res, 2001, 18(5):593-599.
VAN HAL D A, JEREMIASSE E, DE VRINGER T, et al. Encapsulation of lidocaine base and hydrochloride into non-ionic surfactant vesicles(NSVs) and diffusion through human stratum corneum in vitro. Eur J Pharm Sci, 1996, 4(3):147-157.
REPKA M A, GUTTA K, PRODDUTURI S, et al. Characterization of cellulosic hot-melt extruded films containing lidocaine. Eur J Pharm Biopharm, 2005, 59(1):189-196.
KOCHHAR J S, LIM W X S, ZOU S, et al. Microneedle integrated transdermal patch for fast onset and sustained delivery of lidocaine. Mol Pharm, 2013, 10(11):4272-4280.
ZHANG Y, BROWN K, SIEBENALER K, et al. Development of lidocaine-coated microneedle product for rapid, safe, and prolonged local analgesic action. Pharm Res, 2012, 29(1):170-177.
KIM M Y, JUNG B, PARK J H. Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials, 2012, 33(2):668-678.
FRIEDMANN A, CISMAK A, TAUTORAT C, et al. FIB Preparation and SEM investigations for three-dimensional analysis of cell cultures on microneedle arrays. Scanning, 2012, 34(4):221-229.
LARRAÑETA E, MOORE J, VICENTE-PÉREZ E M, et al. A proposed model membrane and test method for microneedle insertion studies. Int J Pharm, 2014, 472(1):65-73.
LI H M. Pharmcodynamics in analgesics of ketoprofen injectable in situ forming gel and pharmcokinetics in dogs. Nanjing:Nanjing Forestry University,2015.
LUTTON R E M, LARRAÑETA E, KEARNEY M C, et al. A novel scalable manufacturing process for the production of hydrogel-forming microneedle arrays. Int J Pharm, 2015, 494(1):417-429.
ZHENG J M. Polymer Science in Pharmaceutics(ҩ�ø߷��Ӳ���ѧ). Beijing:China Medical Science Press, 2000:147.
ZHANG J, MA F S, ZHAN H H. Matrix materials and their composites for dissolvable microneedle construction:a review. Mat Rev(���ϵ���), 2017, 31(19):129-134.
DAVIS S P, LANDIS B J, ADAMS Z H, et al. Insertion of microneedles into skin:measurement and prediction of insertion force and needle fracture force. J Biomech, 2004, 37(8):1155-1163.
UMEDA Y, FUKAMI T, FURUISHI T, et al. Molecular complex consisting of two typical external medicines: intermolecular interaction between indomethacin and lidocaine. Chem Pharm Bull, 2007, 55(5):832-836.
LI J Y, HE Z G, WANG Q F. The effect of glimepiride crystal inhibitor on its solid dispersions. J Shenyang Pharm Univ(����ҩ�ƴ�ѧѧ��), 2017, 34(6):451-460.