Two into one does go: Formulation development of a multipurpose combination vaginal ring releasing dapivirine and metronidazole for prevention of HIV infection and treatment of bacterial vaginosis

被引:5
作者
Zhao, Xinyu [1 ]
Boyd, Peter [1 ]
Bashi, Yahya Dallal [1 ]
Murphy, Diarmaid J. [1 ]
Mccoy, Clare F. [1 ]
Coulter, Sophie [1 ]
Laverty, Garry [1 ]
Malcolm, R. Karl [1 ]
机构
[1] Queens Univ Belfast, Med Biol Ctr, Sch Pharm, Belfast BT9 7BL, North Ireland
关键词
Gardnerella vaginalis; HIV prevention; Sustained release; Multipurpose prevention technology (MPT); IN-VITRO RELEASE; INTRAVAGINAL RING; GENITAL INFLAMMATION; CURE CHARACTERISTICS; MICROBICIDE TMC120; DRUG-RELEASE; DELIVERY; SAFETY; MATRIX; ACQUISITION;
D O I
10.1016/j.ijpharm.2023.123572
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection. With the dapivirine-releasing vaginal ring for HIV prevention now approved in several African countries, here we report formulation development of a next-generation ring product that releases both dapivirine (DPV) and the antibiotic drug metronidazole (MET). Following thermal analysis studies to characterize the phase behaviour of DPV-MET mixtures and rheological analysis to assess the cure characteristics of the active silicone elastomer mixes, matrix-type rings were manufactured containing 25 or 200 mg DPV in combination with 100, 250, 500, 1000 or 2000 mg MET. The results for drug content, in vitro release, mechanical testing, and Gardnerella vaginalis time-kill experiments demonstrate the feasibility of incorporating both DPV and MET in a matrix-type ring formulation and indicate that clinically effective release rates may be possible.
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页数:17
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