Silicone adhesive, a better matrix for tolterodine patches-a research based on in vitro/in vivo studies.

OBJECTIVE: To design and optimize a drug-in-adhesive (DIA) type transdermal patch for tolterodine (TOL) based on acrylic and silicone matrixes. METHODS: Initial in vitro studies were conducted to optimize the formulations. Two types of adhesive matrixes, drug loading, and enhancers were evaluated on the TOL transport across rabbit skin. For in vivo studies, patches were administered to rabbit abdominal skin. Pharmacokinetic assessments were performed based on plasma level of TOL up to 28 h for acrylic patch and 52 h for silicone patch after topical application. RESULTS: The final formulation of acrylic adhesive type patch consisted of 10% TOL (w/w) and 5.8 × 10(-4) mol isopropyl myristate (IPM) and 2.9 × 10(-4) mol Span 80 in per unit gram (mol/g) of adhesive, while 2.5% TOL (w/w) and 2.9 × 10(-4) mol/g IPM for silicone adhesive type patch. Comparison of the pharmacokinetic parameters between two types of patches showed that the steady-state concentration of silicone type patch was 2-fold higher than that of acrylic type patch being 0.97 mg/L versus 0.49 mg/L, and the absolute bioavailability was 27.5% for silicone type patch and 6.3% for acrylic type patch, respectively. In addition, the prediction of in vivo drug level from the in vitro permeation data of silicone adhesive formulation was in good agreement with actual observed concentration data in rabbits. CONCLUSION: These results indicate that the silicone type of TOL patch is an appropriate delivery system for the treatment of overactive bladder (OAB).

Polydimethylsiloxane in the human vocal fold: description of partial explantation.

We describe here for the first time a partial explantation of polydimethylsiloxane in a patient 7 years after implantation caused by faulty positioning of the implant. The histopathologic examination demonstrated that the material that displayed green autofluorescence in hematoxylin-eosin staining was biologically inert and stable. Major inflammatory reaction could not be ascertained.

How to adjust dexamethasone mobility in silicone matrices: A quantitative treatment.

Silicone-based drug delivery systems offer a great potential to improve the therapeutic efficacy and safety of a large variety of medical treatments, e.g. allowing for local long-term delivery of active agents to the inner ear. Different formulation parameters can be varied to adjust desired drug release kinetics. However, often only qualitative information is available on their effects, and product optimization is cumbersome. The aim of this study was to provide a quantitative analysis, allowing also for theoretical predictions of the impact of the device design on system performance. Dexamethasone was incorporated into thin films based on different types of silicones (e.g. varying in the type of side chains and contents of amorphous silica), optionally containing different types and amounts of poly(ethylene glycol) (PEG) (5% or 10%). Furthermore, the initial drug content was altered (from 10% to 50%). In most cases, an analytical solution of Fick's second law could be used to describe the resulting drug release kinetics from the films and to determine the respective "apparent" diffusion coefficient of the drug (which varied from 2×10(-14) to 2×10(-12)cm(2)/s, depending on the system's composition). Thus, the impact of the investigated formulation parameters on drug mobility in the polymeric matrices could be quantitatively described. Importantly, the knowledge of the "apparent" drug diffusivity can be used to theoretically predict the resulting release kinetics from dosage forms of arbitrary size and shape. For instance, dexamethasone release was theoretically predicted from cylindrical extrudates based on a selection of different silicone types. Interestingly, these predictions could be confirmed by independent experiments. Hence, this type of quantitative analysis can replace time-consuming and cost-intensive series of trial-and-error experiments during product optimization. This is particularly helpful, if long-term drug release (e.g., during several weeks, months or years) is targeted.

Silicon and silicone levels in patients with silicone implants.

Although a potential link between silicone gel breast implants and autoimmune connective tissue disease has been suggested, none has been proven. The potential role of silicone as an immune adjuvant remains very controversial. Currently available techniques do not easily allow precise measurements of silicone in tissues. However, all compounds containing silicon (which would include silicone) can be measured accurately. The present study was designed to measure silicon levels in the fibrous capsules of patients with silicone-gel breast implants, saline breast implants and silicone inflatable penile prostheses. Baseline control silicon levels were obtained from the breast tissue of patients undergoing breast reduction, who had no exposure to breast implants. All silicon measurements were carried out using atomic absorption spectrometry with a graphite furnace. The mean silicon levels in 16 breast tissue control samples from 8 patients undergoing breast reduction varied from 0.046 to 0.742 micrograms/g dry weight, with the median mean being 0.0927. The median silicon level in capsules from 6 patients with saline implants was 7.7 micrograms/g (range 36.6). The median silicon level in capsules from 5 patients with silicone inflatable penile prostheses was 19.5 micrograms/g (range 34.8). Although the levels of silicon in capsules of patients with saline breast prostheses and penile implants were higher than in control samples, they were much lower than those from the capsules of the 58 gel implants (median 9979 micrograms/g). Of the 58 silicone gel breast implants (from 20 patients with bilateral implant removal and 18 patients with unilateral removal) which had been inserted from 1974 to 1990, 28 were intact, 8 had pinhole leaks, and 22 were ruptured. Median capsule silicon levels and ranges for all 58 implants, for intact only, for leaking, and for ruptured were: 9979 (152,000), 10,477 (88,703), 6592 (65,396), and 9922 (152,387) micrograms/g respectively. There were no significant differences in silicon levels associated with implant status, duration in situ, or year of implantation. Capsule contracture was not associated with higher levels of capsule silicon. Capsule silicon levels were about 10(6) times higher than previously assayed blood silicon levels. This may be because silicone released from implants remains localized in capsular tissue, or because blood-borne silicone is quickly excreted. Using 29Si nuclear magnetic resonance spectroscopy, no detectable silicone was found in the blood of 7 control women and 7 women with silicone-gel implants (5 with known implant rupture).

Serum silicon levels are elevated in women with silicone gel implants.

The metabolic fate of silicone gel leaked into the body from an implant is unknown. In this study, serum from 72 women with silicone gel breast implants and 55 control women was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed using materials free of silicon. The mean silicon level in controls was 0.13 +/- 0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw or the number of years with implants and silicon levels. The results suggest that elevations of serum silicon are seen in many women with silicone gel breast implants. The kinetics of this elevation and the actual chemical species of the measured silicon remain to be determined.

Pharmacokinetics and effects of 17beta-estradiol and progesterone implants in ovariectomized rats.

UNLABELLED: For the pharmacokinetic evaluation of Silastic capsules, ovariectomized (OVX) rats were implanted subcutaneously with this dosage form containing 17beta-estradiol (5, 10, 15, or 20% in cholesterol, where 5% 17beta-estradiol equals 0.4 mg) or progesterone (20, 40, 110, or 220 mg of crystalline progesterone). The time-course of serum 17beta-estradiol and progesterone released from these capsules in the OVX rat is characterized by an initial increase in serum hormone levels followed by a decline and then an apparent steady-state that persists from 7 to 24 days postimplant. Both hormones have large clearance values (total clearance is 97.7 L/day for 17beta-estradiol and 20.9 L/day for progesterone). For 17beta-estradiol and progesterone only, 11% of the dose was released from the implant after 24 days. Thus, the Silastic membrane represents the rate controlling barrier for these hormones. The relationship between graded doses of 17beta-estradiol or progesterone and serum concentration was linear. Neither tail flick latencies measured at 48, 52.5, and 55 degrees C nor the antinociceptive potency of morphine (ED(50) values) were altered by continuous administration to steady-state of graded doses of 17beta-estradiol or progesterone. We demonstrate how a dose-dependent analysis of some of the behavioral effects of 17beta-estradiol or progesterone can be conducted at steady-state serum hormone concentrations. PERSPECTIVE: We describe a method to obtain sustained serum levels of estrogen or progesterone and the consequences of these sustained hormone levels on acute thermal nociception and the antinociceptive response to morphine. This rat model of hormone replacement may provide insights into the role of these hormones in pathological pain states.

Biodegradation of polysiloxanes in lymph nodes of rats measured with 29Si NMR.

Linear and cyclic polysiloxanes and extracts (free polymer) from a silicone gel-filled implant are used to investigate the reactivity of silicones in vivo. Aqueous emulsions of polysiloxanes and controls (without polysiloxanes) are injected once (day 0, approximately 10% w/v) or six times (starting at day 0, every 14 days, approximately 3% w/v) in the right thigh of rats and the popliteal and lumbar lymph nodes are harvested (3 rats per time point and compound investigated) at 2, 16, 30, 44, 58 and 72 days after the injection. 29Si NMR spectroscopy is used to detect and evaluate the presence of polysiloxanes and their metabolites in the lymph nodes. In addition to the resonance associated with the polysiloxane injected (approximately -20 ppm), the NMR spectra of lymph nodes show new resonances that are attributed to partially hydrolyzed polysiloxanes (-5 to -15 ppm) and silica (-90 to - 120 ppm). These resonances are not present in polysiloxanes emulsions before injection or in the lymph nodes of controls. Our results demonstrate that all polysiloxanes and extracts from silicone gel-filled implants are biotransformed in the lymph nodes, but high molecular weight polymer degrades at a slower rate than oligomers.

Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy.

Gastric emptying of oral silicone dosage forms was studied in humans by gamma-scintigraphy. To achieve a constant and predictable residence time in the stomach, three different formulations based on known concepts such as controlled swelling were investigated. The importance of physical parameters such as size or shape were also examined to assess the feasibility of designing a dosage form for gastric retention. Three shapes: minimatrices, extruded rods and moulded slabs were screened. To label the silicone polymer, two isotopes, used routinely in nuclear medicine departments, were selected: iodine-123 and indium-111. To select the most suitable isotope, the yield and the stability of the labelling were determined in vitro on the pharmaceutical dosage forms. The residence time of these silicone formulations, labelled with iodine and administered in hard gelatine capsules, was monitored in 12 subjects with a gamma camera. The study was performed under fed conditions after ingestion of a standardised meal labelled with indium. The minimatrices provided at least 3 h retention, slabs exhibited 4 h 40 min retention. For the rods the mean residence time in the stomach was around 4 h 20 min. In addition, a correlation was established between the gastric emptying of rods and the half-gastric residence time of meal. On the contrary, such a correlation was not observed for the slabs.

Design of a silicone reservoir intravaginal ring for the delivery of oxybutynin.

Oxybutynin, a drug of choice in the treatment of urinary incontinence, has low oral bioavailability due to extensive first-pass metabolism. A toxic metabolite, N-desethyloxybutynin, has been linked to adverse reactions to oral oxybutynin. This study, therefore, reports on the design of an oxybutynin intravaginal ring (IVR) of reservoir design, comprising an oxybutynin silicone elastomer core encased in a non-medicated silicone sheath, manufactured by reaction injection moulding at 50 degrees C. An unusually high initial burst release of oxybutynin (42.7 mg in 24 h) was observed in vitro with a full length core (100 mg drug loading), with subsequent non-zero order drug release. Use of fractional segment cores substantially reduced the burst effect, yielding linear cumulative drug release versus time plots from days 2 to 14. Thus, a 1/8 fractional segment core gave a 24 h burst of 11.28 mg oxybutynin and, thereafter, zero order release at the target dose of 5 mg/day over 14 days. Two oxybutynin cores, each 1/16 of full length, gave a greater release than a single 1/8 core, due to core segment end effects resulting in an increased surface area for release. The burst release was investigated by determining drug solubilities in the propan-1-ol product of elastomer condensation cure (390 mg/ml) and in the elastomer itself (13.9-20.21 mg/ml, by direct extraction and indirect thermal methods). These high oxybutynin solubilities were considered the major contributors to the burst effect. It was concluded that use of a fractional segment core would allow development of a suitable oxybutynin reservoir IVR.

In vitro release of nonoxynol-9 from silicone matrix intravaginal rings.

The controlled-release characteristics of matrix silicone intravaginal rings loaded with between 100 and 971 mg of nonoxynol-9 have been investigated with a view to developing a ring that may offer a new female-controlled method for the prevention of transmission of sexually transmitted diseases, particularly HIV. Intravaginal rings containing 253, 487 and 971 mg of nonoxynol-9 provided a daily release of 2 mg or more over the 8-day release period, the minimal amount of nonoxynol-9 considered to provide an effective vaginal concentration for the prevention of HIV. Furthermore, the maximum daily release of N9 was about 6 mg, an amount significantly smaller than that observed for other nonoxynol-9 products whose large daily doses may in fact increase the occurrence of HIV by causing epithelial damage to the vaginal tissue. The release mechanism of the liquid nonoxynol-9 from the intravaginal rings has also been investigated and compared to models describing the release of solid drugs from the rings. It has been demonstrated through release studies and surface microscopy that a drug depletion zone is not established in such liquid-loaded intravaginal ring systems, with implications for the release kinetics.

Study on accelerated evaluation system for release profiles of covered-rod type silicone formulation using indomethacin as a model drug.

The purpose of this study was to establish a method allowing rapid evaluation in vitro of the profiles of drug release from covered-rod type silicone formulation (CR silicone formulation), which releases drug for a prolonged period of time. Three CR silicone formulations containing indomethacin (IDM) with different release profiles were used in this study. The release of IDM was accelerated in a mixture of methanol and water (MeOH/water) compared with in phosphate-buffered saline (PBS) added by Tween 20 (PBS-based solvent). The velocity of IDM release varied depending on the composition of the MeOH/water. The change in release velocity was dependent on the solubility of IDM and the permeability of IDM through the silicone membrane. In all the tested formulations, the release rates of IDM estimated in 90% (v/v) MeOH/water were equally 14.6 times faster than those estimated in PBS-based solvent. Release of IDM from the cross-sections and lateral side evaluated by a bi-directional elution cell were accelerated in the MeOH/water in a similar degree. By introducing a common factor to shorten the time axis in all formulations, a fairly good agreement was observed between the two release profiles obtained in the accelerated MeOH/water system and the usual PBS-based solvent system. These results indicate that MeOH/water system enables to reduce the period for evaluation of profiles of drug release from CR silicone formulations in reflecting their release characteristics in usual PBS-based solvent system.

The in vitro characterisation and biodistribution of some non-ionic surfactant coated liposomes in the rabbit.

The degree of adsorption of some novel silicone glycol copolymers onto polystyrene microspheres was studied and compared with the sorption onto small unilamellar vesicles (SUVs) composed of egg phosphatidylcholine (EPC) and prepared by the detergent dialysis technique. These non-ionic surfactants are 'comb' polymers of the ABn type where A is a silicone chain with n pendant polyglycol chains (B). Photon correlation spectroscopy was used to measure the adsorbed layer thickness (delta h) following polymer sorption from aqueous solutions. delta h on latex particles was a function of the length of the polymer hydrophilic chains. Upon incubation with SUVs, delta h of the different polymers was similar (3 nm) and significantly less (two sample t-test, p < 0.01) than the corresponding delta h on the polystyrene latex which could be attributed to the penetration of the polymers into the outer phospholipid bilayer. The glycol chains of the silicone polymers are assumed to be in a helical and planar position. Efflux of 5(6)-carboxyfluorescein from EPC liposomes was increased by the presence of these polymers. The highest retention (49% at 5 h) was obtained with SUVs coated with the silicone polymer possessing the highest glycol content and the longest ethylene oxide chains. Sterically stabilised vesicles were also formed by coating dipalmitoyl phosphatidyl-choline (DPPC)/cholesterol (Chol) (molar ratio 1:1) with two of these silicone glycol copolymers and Poloxamer 338. The liposomes were labelled with 67gallium-desferrioxamine (67Ga-DF). Incubation of radiolabelled Poloxamer 338-coated vesicles in saline or serum at 37 degrees C for 24 h resulted in less stable liposomes compared to the more stable non-coated or silicone coated vesicles. Following intravenous (i.v.) administration in rabbits, free 67Ga-DF rapidly disappeared from the circulation (half-life = 41.4 min) and accumulated in the bladder. Two populations of vesicles were prepared (136 +/- 2.9 nm and 100 +/- 1.4 nm). 24 h after i.v. injection of the different formulations of the 100 nm liposomes in rabbits, 20-27% of the activity was retained in blood. The silicone polymer with the highest glycol content and the longest ethylene oxide chains showed the longest half-life (21.4 h). Using gamma scintigraphy, the liver/spleen uptake of the 136 nm non-coated vesicles was 57% which was significantly reduced to 37% upon coating the liposomes with the silicone glycol copolymers. At 30 min post i.v. injection, approximately 10% of the activity was associated with the heart/lung region irrespective of liposome size or polymer coating.(ABSTRACT TRUNCATED AT 400 WORDS)

The piscine bioconcentration characteristics of cyclic and linear oligomeric permethylsiloxanes.

Using a conventional "resaturation" method whereby aquarium water was continuously passed through a column containing sand or fine glass beads coated with cyclic and linear permethylsiloxanes, their uptake levels by rainbow trout and fathead minnows have been compared. Because of the uncertainty associated with defining the actual aqueous concentrations of such poorly soluble substances, this study was focused on defining the "attainable uptake" levels from saturated solutions rather than precise definition of actual bioconcentration factor values. Although cyclic Me2SiO-oligomers accumulated to a greater extent in fish than did comparable linear oligomers, uptake decreased sharply with increasing molecular weight. Thus, in the cyclic series (Dx), order of magnitude decreases were observed for each incremental molecular weight increase; i.e., for the compounds D4, D5, and D6 uptake levels of approximately 200, 20 and 2 ppm, respectively, were observed. Uptake of D8 was below our detection limit of 300 ppb. In the linear series, uptake of the tetramer MD2M was an order of magnitude less than observed for D4 and little or no uptake (i.e., less than 0.5 ppm) was observed for MD3M, MD4M and MD7M. The branched oligomer M3T exhibited levels comparable to its unbranched isomer MD2M, while M4Q was more comparable to the D6 uptake of 1-2 ppm. Very similar uptake levels of D5 resulted with and without a surfactant, even though the surfactant afforded a 20-fold increase in the D5 content of the water. This suggests that bio-availability is defined by the amount present in true solution as individual molecules and is not affected by the presence of aggregates or micelles. The highly inverse relationship observed in this study between uptake and molecular weight is strongly supportive of earlier estimates of a limiting molecular weight of about 600. These findings also strongly contradict a recent Japanese study, which concluded that bioconcentration not only occurred but actually increased with molecular weight in a series of commercial polydimethylsiloxane fluids. Also contrary to a recently published inference of biotransformation in fish, no evidence for such phenomena was observed in this study.

Effects of silicone emulsifiers on in vitro skin permeation of sunscreens from cosmetic emulsions.

The effects of different silicone emulsifiers on the in vitro permeation through human skin of two sunscreens (octylmethoxycinnamate, OMC, and butylmethoxydibenzoylmethane, BMBM) were investigated from cosmetic emulsions. The formulations being tested were prepared using the same oil and aqueous phase ingredients and the following silicone emulsifiers: dimethicone copolyol and cyclomethicone (emulsion 1), cetyldimethicone copolyol (emulsion 2), polyglyceryl-4-isostearate and cetyldimethicone copolyol and hexyllaurate (emulsion 3), lauryldimethicone copolyol (emulsion 4), and cyclomethicone and dimethicone copolyol (emulsion 5). The cumulative amount of OMC that permeated in vitro through human skin after 22 h from emulsions 1-5 decreased in the order 2 approximate, equals 1 > 5 > 4 approximate, equals 3 and was about twofold higher from emulsion 2 compared to emulsion 4. As for BMBM, no significant difference was observed in regard to its skin permeation from the emulsions being tested. In vitro release experiments of OMC and BMBM from emulsions 1-5 were performed through cellulose acetate membranes using Franz diffusion cells. Emulsions 1-3 showed an initial slow release of BMBM followed by a fast release phase, while the release of OMC showed a different pattern since the sunscreen was released very rapidly at the beginning of the experiment and then a plateau was observed followed by a second step of fast release. A pseudo-first-order release rate was observed only for BMBM from emulsion 4, while emulsion 5 released very small amounts of both sunscreens during 22 h. These findings could be attributed both to changes in sunscreen thermodynamic activity in the vehicle and to modified interactions between the active ingredient and the formulation components. The results of this study suggest that the type of silicone emulsifier used to prepare sunscreen emulsions should be carefully chosen in order to prevent the percutaneous absorption of sunscreens from these cosmetic formulations.

Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice.

Nano-sized titanium dioxide particles (TiO(2)) are widely used in cosmetics, sunscreens and food additives. We previously reported that topical application of non-coated rutile type TiO(2) did not exhibit a promoting effect on ultraviolet B-initiated skin carcinogenesis in rats, and that this was likely due to lack of penetration of TiO(2) into the epidermis. In the present study, we examined the promoting effect of silicone coated TiO(2 )(sTiO(2)) suspended in silicone oil and non-coated TiO(2 )(ncTiO(2)) suspended in Pentalan 408 on a two-stage skin chemical carcinogenesis model: sTiO(2) suspended in silicon oil forms smaller particles than ncTiO(2) suspended in Pentalan because of the smaller sizes of aggregates formed. The model used skin carcinogenesis-sensitive human c-Ha-ras proto-oncogene transgenic mice (rasH2) and rats (Hras128) and their wild-type counterparts and CD-1 mice to test the effects of topical application of TiO(2). Animals were initially treated with a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) and then with 0, 10, or 20 mg sTiO(2) (mice) or 0, 50, or 100 mg ncTiO(2) (rats). The incidence and multiplicity of skin tumors (squamous cell papilloma and carcinoma) did not increase over DMBA alone controls in skin carcinogenesis-sensitive mice or rats or wild-type animals. Analysis of rat skin indicated that sTiO(2) and ncTiO(2) did not penetrate though either healthy or damaged skin. Furthermore sTiO(2) did not penetrate an in vitro human epidermis model. Our results indicate that treatment with sTiO(2) or ncTiO(2) did not promote skin carcinogenesis in mice or rats, probably due to lack of penetration through the epidermis.

Metal ion release kinetics from nanoparticle silicone composites.

Metal ion release kinetics from silver and copper nanoparticle silicone composites generated by laser ablation in liquids are investigated. The metal ion transport mechanism is studied by using different model equations and their fit to experimental data. Results indicate that during the first 30 days of immersion, Fickian diffusion is the dominant transport mechanism. After this time period, the oxidation and dissolution of nanoparticles from the bulk determine the ion release. This second mechanism is very slow since the dissolution of the nanoparticle is found to be anisotropic. Silver ion release profile is best described by pseudo-first order exponential equation. Copper ion release profile is best described by a second order exponential equation. For practical purposes, the in vitro release characteristics of the bioactive metal ions are evaluated as a function of nanoparticle loading density, the chemistry and the texture of the silicone. Based on the proposed two-step release model, a prediction of the release characteristics over a time course of 84 days is possible and a long-term ion release could be demonstrated.

In vitro and in vivo biological performance of collagen-chitosan/silicone membrane bilayer dermal equivalent.

Skin loss or damage affects severely the life quality of human being and can even cause death in many cases. We report here a bilayer dermal equivalent (BDE) composed of collagen-chitosan porous scaffold and silicone membrane, which can effectively induce the regeneration of dermis in an animal model of full thickness skin loss. The in vitro biosecurity test showed that the BDE had no cytotoxicity, and no remarkable sensitization and irritability. In vitro cell culture proved that the BDE had good biocompatibility to support the proliferation of fibroblasts. Animal test was performed on Bama miniature pig skin. Gross view and histological sections found plenty of fibroblasts and extracellular matrix in the regenerative scaffold after transplantation of the BDE for 4 weeks. Immunohistochemistry results proved that the BDE has the ability to support the angiogenesis of the regenerated dermis. All these results indicate that the BDE might be a promising equivalent in treating dermal loss.

Novel drug delivery device using silicone: controlled release of insoluble drugs or two kinds of water-soluble drugs.

Drug release mechanism from silicone carrier differs depending on physicochemical properties of the drug. So far, there have been few reports on controlled release of insoluble drug and on simultaneous release of two kinds of water-soluble drugs. The purposes of this study are to establish methods for (1). continuous release of insoluble drug, and (2). release of two kinds of water-soluble drugs from silicone carrier. Polystyrene beads (PSTB) and proteins such as interferon (IFN) and human serum albumin (HSA) were used as model drugs. PSTB was released from silicone only when citric acid (CA) and sodium bicarbonate (SB) existed as additives. The release patterns of IFN and HSA were almost same in the case of matrix and covered-rod formulations, but double-layered formulation released them in different patterns. As far as we are aware, this is the first report on the release of insoluble drug from silicone and the controlled release of two kinds of water-soluble drugs.