Investigation of Polycaprolactone Matrices for Intravaginal Delivery of Doxycycline

On Drug-Base Incompatibilities During Extrudate Manufacture and Fused Deposition 3D Printing

“…Furthermore, PCL has reported use in pharmaceutical dosage forms. In 2015, Pathak and co-workers successfully manufactured PCL matrices loaded with doxycycline to be administered via the vaginal route for the treatment of sexually transmitted infections [29]. Thus, PCL could prove to be a suitable excipient for use in drug eluting constructs in the field of FDM.…”

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease

“…A large burst effect was previously observed for PCL matrices loaded only with metronidazole (35-65%) along with low drug release rates over a period of 14 days [24]. In contrast, doxycycline release from singlyloaded PCL matrices was more uniform [25], resulting in gradual delivery of 65-75% of the drug load over 14 days. Thus PCL matrices were loaded with increasing concentrations of metronidazole at constant doxycycline loading in the present study to enhance the rate and quantity of metronidazole release.…”

“…Poly (ɛcaprolactone) (PCL) has been studied extensively for controlled drug delivery applications in the form of micro-and nanoparticles, fibers and matrices [23] and offers advantages for the production of intravaginal drug delivery devices because of its biocompatibility, ease of processing and relatively low processing temperatures. PCL matrices prepared by rapid cooling techniques have previously been investigated for vaginal delivery of individual antibacterials (metronidazole and doxycycline) [24,25] antifungal (miconazole) [26] and antiviral agents (tenofovir and acyclovir) [27,28]. Here we describe the development of PCL matrices, loaded with a combination of metronidazole and doxycycline hyclate.…”

“…Here we describe the development of PCL matrices, loaded with a combination of metronidazole and doxycycline hyclate. The overall objectives of the research were to characterise the release behaviour of each compound and their antibacterial activity in vitro and thus assess the potential utility of the materials for production of IVRs in the Cylindrical PCL matrices loaded with combinations of metronidazole and doxycycline hyclate were prepared according to our previously reported method [25]. A 15% w/v solution of PCL in acetone was produced by heating at 45°C.…”

“…The crystallinity of the PCL phase was reduced by over 50% on incorporation of both metronidazole and doxycycline at loadings of 10% w/w (Table 1), indicating interference with PCL crystal nucleation and growth. When loaded individually into PCL matrices, doxycycline has been found to reduce crystallinity [25] while metronidazole increases crystallinity [24] compared with drug-free PCL matrices. Indeed, in the present study, PCL crystallinity increased as the concentration of metronidazole in the matrices increased from 10 to 20% (Table 1), supporting the hypothesis that metronidazole acts as a nucleating agent for crystallisation of PCL .…”