Table 1.

Reported strategies for modulation of drug release from silicone elastomers.

Strategy	Mechanism	Description	References
Incorporation of hydrophilic excipients	Introduce pores to create water channels	HPMC, sucrose, or glycine dispersed in silicone to increase bovine serum albumin (BSA) release	Carelli et al. 1989; Woolfson et al. 2006; Brook et al. 2008; Di Colo 1992; Morrow et al. 2011; Snorradóttir et al. 2011; Murphy et al. 2016; Mazurek et al. 2018; McBride, Boyd, et al. 2019; Mazurek, Frederiksen, et al. 2021; Mazurek, Yuusuf, et al. 2021
Hydrophilic polymer blending	Blend silicone with polymers to enhance water uptake and drug mobility	Silicone–polyethylene glycol (PEG) copolymer matrices used to enhance the permeability of the silicone elastomer to hydrophilic and ionic species	Li and Peck 1989; Rajendra et al. 2010; Forbes et al. 2014; Mikolaszek et al. 2020
Porous matrix	Introduction of pores to promote diffusion	Silicone containing PEG8000-leached pores to enhance acetaminophen and tartrazine release	Dahl and Sue 1992; Nemati et al. 2014
Use of co-solvents or solubilizers	Enhancing drug mobility by reducing matrix–drug interactions and lowering diffusion activation energy	Glycerol and NaCl incorporated into silicone elastomer implants to enhance release of melatonin and estradiol	Hsieh et al. 1985; Maeda, Brandon, et al. 2003
Incorporation of preformed hydrogel particles	Embedding hydrophilic hydrogel particles that swell upon hydration to form aqueous diffusion paths	Polyacrylamide hydrogel particles incorporated in silicone rubber to enhance progesterone release	Lopour et al. 1990; Mashak 2008
Drug molecular complexation	Modify drug solubility and partitioning via inclusion complexation	Azelaic acid-hydroxypropyl-β-cyclodextrin complex used in silicone membrane to enhance the release of azelaic acid	Manosroi et al. 2005
Surface hydrophilization	Graft hydrophilic groups on silicone surface	PEGylation of silicone elastomer to modulate triclosan release	McBride et al. 2009
Drug particle size engineering	Altering particle size to modify surface area and diffusion dynamics	Larger particle size of interferon/human serum albumin (HSA) powder in silicone elastomer to increase release rate of IFN	Kajihara et al. 2000; Farahmandghavi et al. 2019
Polymer microstructure engineering	Using additives/fillers to modify polymer crystallinity, viscosity, drug affinity, and diffusion paths	Silica, PEG, or silicone oil used to modify polydimethylsiloxanes for optimized levonorgestrel release	McConville et al. 2012; Tolia and Li 2012; Ma et al. 2018; Fanse et al. 2024
Formulation geometry design	Control of release via physical structure to maintain a constant diffusion area	A 1/8 fractional segment core design of vaginal ring to achieve zero-order release of oxybutynin	Kajihara et al. 2001, 2003; Maeda, Ohashi, et al. 2003; Woolfson et al. 2003
Stimuli-responsive additives	Triggering release via stimuli, such as pH, enzymes, or temperature	N-isopropylacrylamide hydrogel particles incorporated into a silicone rubber membrane as temperature-responsive additives that enhance release at temperature > 34 °C	Hu et al. 2000; Nemati et al. 2014