Zero-order Release Rate Research Articles

A Novel Gastro-Retentive Osmotic Pump Capsule Using Asymmetric Membrane Technology: In Vitro and In Vivo Evaluation

The purpose of this paper is to develop a novel gastro-retentive osmotic pump capsule using asymmetric membrane technology. The physical characteristics of capsule walls and drug delivery behaviors of the system were compared through different coating solutions. The formulation with the glycerin and diethyl phthalate ratio of 5:4 appears to be the best. The thickness of asymmetric membranes was evaluated by withdrawing speed. The relation between the two can be fitted to a linear model. The floating abilities were investigated through filling polyethylene oxide of different molecular weight into the capsules. WSR N-80 (molecular weight 200000) is chosen for the longest floating time. Central composite design-response surface methodology was used to investigate the influence of factors on the responses. The in vivo pharmacokinetics were studied in beagle dogs. A second-order polynomial equation was fitted to the data, and the actual response values are in good accordance with the predicted ones. The optimized formulation displays a complete drug delivery, zero-order release rate and 12 h floating time. The in vivo study results clearly indicate the controlled and sustained release of Famotidine from the system, and the relative bioavailability of this preparation is about 1.605 in comparison to that of the marketed preparation.

A novel gastric-resident osmotic pump tablet: In vitro and in vivo evaluation

A novel famotidine gastric-resident osmotic pump tablet was developed. Pharmaceutical iron powder was used as a gas-formation and density-increasing agent. Central composite design-response surface methodology was used to investigate the influence of factors, i.e., polyethylene oxide ( Mw 1,000,000) content, NaCl content, iron powder content and weight gain, on the responses including ultimate cumulative release and correlation coefficient of drug release profile. A second-order polynomial equation was fitted to the data and actual response values are in good accordance with the predicted ones. The optimized formulation displays a complete drug delivery and zero-order release rate. Gamma scintigraphy was selected as the method to monitor in vivo gastric residence time of the 99mTc-labeled system in Beagle dogs. It was observed that the system can retain in stomach for an extended period of 7 h after administration compared with conventional tablets. The present investigation suggests that water-insoluble drug can be delivered from single-layer osmotic pump tablets completely due to the push power of the hydrogen gas generated by the reaction of the iron and gastric fluid. And iron powder can increase the system density which is over 2.5 g cm −3, making the system resident in stomach to prolong the drug delivery time in absorption zone.

Synthesis and characterization of nanoporous polycaprolactone membranes via thermally- and nonsolvent-induced phase separations for biomedical device application

A constant and well-controlled drug release rate is of paramount importance to implantable drug delivery systems in finding the remedy against chronic diseases. This paper describes the synthesis and potential application of nanoporous poly(caprolactone) (PCL) membranes to achieve the zero-order release rate. Nanoporous PCL membranes were prepared via the combination of thermally- and nonsolvent-induced phase separations. In the membrane preparation, 1,4-dioxane and 2-methoxyethanol were used as solvent and nonsolvent, respectively, resulting in uniform nanoporous membranes and consistent lysozyme diffusion using a Teflon plate for membrane casting. Pore connectivity was improved significantly when coagulation bath temperature was lowered from 35 to 5 °C. By using a 5 °C water coagulation bath in the wet-process precipitation, the average pore size reduced from about 90 to 55 nm while increasing the casting solution concentration from 15 to 25 wt% PCL. Thus, by varying the polymer concentration of the casting solution, the lysozyme release rate was well controlled. The potential of nanoporous PCL membranes for an implantable drug delivery device to achieve the zero-order release rate was demonstrated in this study.

Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle after Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

Corticosteroids (CS) effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX) rats were given single doses of 50 mg/kg methylprednisolone (MPL) intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1), uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase isoenzyme 4 (PDK4), fatty acid translocase (FAT) and glycerol-3-phosphate acyltransferase (GPAT) dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N)) and transcription factors. The oscillatory feature of endothelin-1 (ET-1) expression was depicted by a negative feedback loop. These integrated models provide testable quantitative hypotheses for these regulatory cascades.

Analysis of nano drug carriers towards optimum release rate

The aim of this paper is to determine which polymer shape (sphere, hemisphere, cylinder, tablet, cuboid, tetrahedron or octahedron) is best for zero kinetics drug delivery and for sustained nanoparticle release. We applied the Carslaw and Jaeger heat diffusion equations of a sphere with same order of its effective surface area to volume ratio as a reference, to predict how drug delivery would occur in other shapes. The assumption of the heat diffusion analogy in the present study of negligible drug particles is sensible since the drug at nano scale is tiny and thus nearly ‘massless’. From tests involving changing the micro-carrier configuration, we can confirm that shape is an important factor to consider when examining drug release rates, to achieve zero-order design. The preliminary analysis suggests that a hemisphere shape is more promising in achieving zero-order drug release rate, followed by a tablet shape of L = 2Rs, 3Rs, a tetrahedron, a cylindrical shape with L = 3Rs, 2Rs, a sphere, a cuboid shape with L = 3Rs, 2Rs, and finally an octahedron. This is due to the larger effective surface area, given the same parameters and surrounding conditions. In other words, a hemisphere shape reaches zero order in the shortest possible time and thus permits sustained zero-order particle release rate. Based on the ratio between the surface area of a micro-carrier and its volume, we further derived the drug release equation of cylinder/tablet shaped micro-carrier. By introducing h as an index of the similarity of the drug release rate to a desirable zero-order drug release rate, we obtained a relationship between different length/radius (L/R) values of cylinder/tablet shapes and the index h. From this relationship, we find the best L/R ratio that can achieve a drug release process most similar to a zero-order drug release process. Future work is to include optimization of the lipid matrixes.

Characterization of 5-Fluorouracil Release from Hydroxypropylmethylcellulose Compression-Coated Tablets

Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (Tlag), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of Tlag and increase of k. Tlag and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in Tlag and decrease in k. There was good fitting of a linear model for each of the four variables W, D, Tlag, and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.

Inward release polymer matrix covered by a permeable membrane: a possible zero-order controlled release device

An inward release polymer matrix with its aperture covered by a drug-permeable membrane is proposed as a potential zero-order controlled release device. The presence of the membrane has the effects of modifying the rate of release so that it is closer to zero order, and alleviating the problem of initial burst. Applying a Landau transformation, the present moving boundary problem is transformed in to a fixed boundary one, and the resultant problem is solved numerically by a finite difference scheme. We show that assuming drug release occurs under a pseudosteady-state condition is appropriate if the ratio (inner radius of device/outer radius of device) is small and/or the mass transfer resistance of the membrane is large. The applicability of two kinds of pseudosteady-state assumptions is discussed. The performance of the pseudosteady-state based on the rate of release is better than that based on the moving front. The region of the present device where the rate of release remains constant increases with the decrease in the ratio (inner radius of device/outer radius of device) and/or the increase in the mass transfer resistance of the membrane. Also, the higher the degree of overloading the longer the device is capable of maintaining a zero-order release rate.

Effect of lactide/glycolide monomers on release behaviors of gentamicin sulfate-loaded PLGA discs

In order to develop the desirable drug release patterns such as no lag time and exact zero-order release rate, gentamicin sulfate (GS)-loaded poly( d, l-lactide-co-glycolide) (PLGA) discs containing lactide monomer (LM) or glycolide monomer (GM) were prepared. LM or GM was applied for the controlling drug release pattern due to its non-toxic and biodegradable nature. Water absorption, mass loss, pH change, and morphology of discs were examined to study the effect of LM or GM addition. GS release showed near zero-order profile in the GS-loaded polymeric discs prepared in the presence of LM or GM (10%). The channel of GS-loaded PLGA containing LM or GM was formed by the dissolution of LM or GM. Water uptake of disc increased till 21 days from the beginning of the test. The pH variations of media declined in the same manner with the result of mass loss. The antibiosis of GS was also confirmed by bacterial inhibition zone test using the prepared polymeric discs. From these results, we expected that the polymeric discs containing LM or GM would be a good dosage form as a topically implantable device which can get rid of lag period from PLGA matrix.

Antinociceptive effects of hydromorphone, bupivacaine and biphalin released from PLGA polymer after intrathecal implantation in rats

Intraspinal drug delivery, based on the concept of controlling pain by delivering drug to a nociceptive target rich in opioid and other relevant receptors is increasingly used clinically. The therapeutic ratio for opioids or other centrally acting agents is potentially greater if they are administered intrathecally (i.t.) than outside the central nervous system (CNS). The present study was designed with the ultimate goal of formulating a controlled release system for intrathecal analgesia characterized by effectiveness, rapid onset and few side effects for chronic pain control. A biodegradable copolymer poly( l-lactide-co-glycolide) (PLGA) was used to prepare a rod-shaped drug delivery system containing hydromorphone (HM), bupivacaine (BP), both HM and BP, or biphalin (BI). In vitro drug release kinetics of these systems showed a zero-order release rate for HM and BP from PLGA (85:15) rods. Drug-loaded rods were implanted i.t. Control groups received only placebo implants. Measurement of analgesic efficacy was carried out with tail flick and paw-withdrawal tests. In vivo studies showed potent, prolonged analgesia in comparison to controls for all active treatments. Analgesic synergy was observed with HM and BP. With further refinements of drug release rate, these rods may offer a clinically relevant alternative for intrathecal analgesia.

Design of an injectable system based on bioerodible polyanhydride microspheres for sustained drug delivery

The fabrication, morphological characterization, and drug release kinetics from microspheres of three bioerodible polyanhydrides, poly[1,6-bis( p-carboxyphenoxy)hexane] (poly(CPH)), poly(sebacic anhydride) (poly(SA)), and the copolymer poly(CPH-co-SA) 50:50 (CPH:SA 50:50) is reported. The fabrication technique yields microspheres with different morphologies for each of the three polymers studied, ranging from very smooth exterior surfaces for poly(CPH) to coarse surface roughness with large pores for poly(SA). Release profiles for the model drug, p-nitroaniline are also different for each polymer. The release profile from poly(CPH) has a large initial burst and shows little additional release after 2 days. The release from poly(SA) is nearly zero-order and lasts for about 8 days. The release profile from CPH:SA 50:50 shows a relatively small burst and then exhibits zero-order release for about 1 month. The different release profiles are attributed to both polymer erosion rates and drug distribution characteristics of the microspheres. Tailored release profiles of a burst followed by zero-order release are obtained by appropriately combining the microspheres. This technique enables independent modulation of both the burst and the zero-order release rate by varying the number of poly(CPH) and poly(SA) microspheres respectively. Additionally, the zero-order release can be extended from about a week to a month by including CPH:SA 50:50 microspheres.

Development of Extended Release Dosage Forms Using Non-Uniform Drug Distribution Techniques

ABSTRACTDevelopment of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37°C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

Assessment of biodegradable controlled release rod systems for pain relief applications

Control of chronic, severe pain is a difficult and important clinical problem for most patients, especially those with cancer. Although current applications are insufficient for a satisfactory solution to this problem, the rate of disease incidence is increasing worldwide, thus making the problem more apparent. Based on this fact, this study was designed with the ultimate goal of formulating a controlled release system of pain relievers, mainly opioids, for the local treatment of pain to achieve satisfactory, fast, and less side effect-related relief and to provide a better life status for chronic pain patients. Two copolymers of a biodegradable polymer poly(L-lactide-coglycolide) (PLGA) were used to prepare an implantable rod type drug release system containing either an analgesic or anesthetic type of pain reliever. In vitro drug release kinetics of these systems were studied. It was observed that release from PLGA 85 : 15 was more zero-order than it was from PLGA 50 :50. A zero-order release rate was obtained for codeine, hydromorphone, and bupivacaine from PLGA (85 :15) rods. They, however, were released from PLGA (50 :50) rods with Higuchi kinetics. The drug solubility was also influential on release rate, as shown by the zero-order morphine release from PLGA (50 :50) rods. Scanning electron micrographs (SEMs) of the monolithic rods revealed erosion of the rods and the removal of drug crystals from the rod structure.

Pharmacodynamics and pharmacogenomics of methylprednisolone during 7-day infusions in rats.

An array of adverse steroid effects was examined on a whole body, tissue, and molecular level. Groups of male adrenalectomized Wistar rats were subcutaneously implanted with Alzet mini-pumps giving zero-order release rates of 0, 0.1, and 0.3 mg/kg/h methylprednisolone for 7 days. The rats were sacrificed at various times during the 7-day infusion period. A two-compartment model with a zero order input could adequately describe the kinetics of methylprednisolone upon infusion. Blood lymphocyte counts dropped to a minimum by 6 h and were well characterized by the cell trafficking model. The time course of changes in body and organ (liver, spleen, thymus, gastrocnemius muscle, and lungs) weights was described using indirect response models. Markers of gene-mediated steroid effects included hepatic cytosolic free receptor density, receptor mRNA, tyrosine aminotransferase (TAT) mRNA, and TAT levels. Our fifth-generation model of acute corticosteroid pharmacodynamics was used to predict the time course of receptor/gene-mediated effects. An excellent agreement between the expected and observed receptor dynamics suggested that receptor events and mRNA autoregulation are not altered upon 7-day methylprednisolone dosing. However, the model indicated a decoupling between the receptor and TAT dynamics with this infusion. The strong tolerance seen in TAT mRNA induction could be partly accounted for by receptor down-regulation. An amplification of translation of TAT mRNA to TAT and/or a reduction in the enzyme degradation rate could account for the observed exaggerated TAT activity. Our results exemplify the importance of biological signal transduction variables in controlling receptor/gene-mediated steroid responses during chronic dosing.

Sustained release ketoprofen microparticles with ethylcellulose and carboxymethylethylcellulose

Microparticulate systems for sustained release of ketoprofen were prepared and evaluated by monitoring drug release in the JP XIII second fluid, pH 6.8. All the microparticulate dosage forms were prepared using ketoprofen in the form of calcium salt (KP-Ca). Simple ethylcellulose microparticles of KP-Ca (EC-MP) exhibited the fairly rapid release in the first phase with slower release in the late period. Most of the drug was released from EC-MP showing high drug content. For polymer-coated microparticles of ketoprofen, Eudragit microparticles of KP-Ca (ER-MP) were first prepared, and then coated with ethylcellulose or with a mixture of carboxymethylethylcellulose and ethylcellulose to produce ethylcellulose-coated (EC-coat) and the mixture-coated microparticles (CMEC/EC-coat), respectively. Some polymer-coated microparticles showed drug release at nearly zero-order rate. Especially, CMEC/EC-coat prepared at a CMEC:EC ratio of 1:1 (w/w), named formation I, could supply the drug constantly and efficiently for about half a day except for an initial rapid release. When formation I was administered intraduodenally to rats, the plasma concentration of ketoprofen could be maintained at a nearly constant level. Kinetic analysis demonstrated that formation I showed a nearly zero-order release rate in vivo consistent with that observed in vitro.

A novel approach for constant rate delivery of highly soluble bioactives from a simple monolithic system

A novel monolithic drug delivery system for highly water-soluble bioactive agents to follow pH-independent zero-order kinetics is described. The system utilizes a hydrophilic gel-based swellable polymeric material (polyethylene oxide), a model drug (metoprolol tartrate, 100% water soluble at 25°C) and different electrolytes, such as sodium carbonate and/or pentasodium tripolyphosphate. Based on the induction of in situ intra-gel chemical reactions between different ionic species, drug and polymer, a heterogeneous structure manifested as ‘peripheral boundary stiffening,’ is accomplished. The consequence of these interactions essentially include the development of gradient-controlled matrix swelling as elucidated through textural profiling, which may contribute to inhibition of drug solubility and its outward diffusion. Analysis of textural profiles and photomicroscopy distinctly provides information on the disposition of peripheral boundary densification for the electrolyte-containing matrices. Electrolytic conductivity measurements performed with the simultaneous analysis of matrix swelling showed that sodium carbonate forms a highly reactive matrix within the first 3 h of medium penetration. On the other hand, larger molecules such as pentasodium tripolyphosphate maintain a constant conductivity level, which may be related to its lower solubility and diffusion in comparison to sodium carbonate. Based on model fitting and statistical analysis, it is shown that drug release kinetics were adequately described by Mt/M∞=k0t, with zero-order release rate constant k0 of 0.054 h−1. This novel approach in formulation development could potentially be used for constant rate delivery of highly soluble bioactive agents over an extended period for specific biopharmaceutical needs.

Combined denitrification and phosphorus removal in a biofilter

A lab-scale biofilter was run continuously for 1½ years for combined denitrification and phosphorus removal. lternation between anaerobic and anoxic (nitrate) conditions was used to obtain an enriched culture of denitrifying, phosphate accumulating organisms. Batch experiments were performed to test the importance of diffusion and zonation in the biofilm. Half- and zero-order anaerobic phosphate release and anoxic phosphate uptake rates were verified, which was taken as an indication of a zonated biofilm. To investigate the practical applicability of the process, the development of a computer model is necessary due to the high complexity of the process. AQUASIM is suitable for this purpose. The model can provide insight into what goes on inside the biofilm and act as a tool when predicting required tank sizes, optimal phase lengths and biofilm thickness etc. for a large-scale system. For control of the process, on-line measurements and computer control of the system are essential.

Development of a membrane-controlled transdermal therapeutic system containing isosorbide dinitrate

The formulation of a transdermal delivery system for isosorbide dinitrate (ISDN) was examined. It was found that the target release rate should be 4.01 mg/h per 20 cm 2 for optimal dosing. In order to reach such this zero order release rate, a membrane permeation controlled transdermal therapeutic system (TTS) formulation was developed, with ethylene vinyl acetate copolymer (EVAC) and polyethylene (PE) membranes as rate controlling membranes; a carbomer gel was used as the drug reservoir. The release of ISDN from this drug delivery device was studied in vitro using FDA recommended method. PIB adhesive on the EVAC or PE membrane caused a decreased flux of ISDN; the release kinetics fitted Higuchi matrix kinetics. TTS with EVAC membrane release ISDN at a rate much lower than the calculated target release rate, but with PE membranes, the release rate was very close to the target. Release rate studies have revealed that, as the VA content in EVAC membrane increased, the flux of ISDN increased. All these results were compared with the commercial product Frandol ® Tape S from Japan. It was found that the release rate of Frandol was close to target release rate and fitted matrix kinetics. These results suggested that TTS that contain PE membrane as rate controlling membrane, polyisobutylene (PIB) adhesive and carbomer gel as a reservoir can be applicable as a TTS for ISDN.

Controlled release of insect sex pheromones from paraffin wax and emulsions

Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27°C, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38°C, zero-order release was observed. At 38°C and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.

Pharmacokinetic evaluation in dogs of theophylline in a novel zero-order release core-in-cup tablet.

A new core-in-cup tablet that is manufactured from a novel adjustable punch, has been formulated and evaluated for its ability to release with subsequent absorption of theophylline via a zero-order rate of absorption. The core-in-cup tablets were compared with core only tablets and immediate release capsules. Pharmacokinetic parameters used to test the effectiveness of the formulations included, elimination rate, rate and kinetic order of absorption, relative availability as compared with an immediate release capsule of pure theophylline, and percentage area under the curve fluctuation (%AUCF) at steady state. The correlation coefficient, Akaike's information criterion (AIC) and the F-ratio probability were used to test the applicability of a zero-order, first-order, or square root of time model, for the rate of release of theophylline from the core-in-cup and core only tablets. The zero-order rate model was most applicable to the core-in-cup tablet, whereas the square root of time release model was most applicable to the core only tablet. The average %AUCF for the core-in-cup tablet was 9.26+/-3.15 while that for the core only tablet was 16.19+/-2.37 (p = 0.0545). The results of this study suggest that the core-in-cup tablet is a versatile zero-order release rate dosage form that are simple to produce.

Silicone rubber/hydrogel composite ophthalmic inserts: preparation and preliminary in vitro/in vivo evaluation

The present report describes the development and in vitro/in vivo testing of rod-shaped mucoadhesive ophthalmic inserts fitting the upper or lower conjunctival fornix. Cylindrical devices (diameter 0.9 mm, length 6–12 mm, weight 3–8 mg) all containing 0.8 mg oxytetracycline HCl (OXT) were prepared from appropriate mixtures of silicone elastomer, OXT and sodium chloride as release modifier. A stable polyacrylic acid (PAA) or polymethacrylic acid (PMA) interpenetrating polymer network (IPN; 30 or 46% w/w) was grafted onto the inserts' surface by treatment with a mixture of acrylic (or methacrylic) acid and ethylene glycol dimethacrylate in xylene at 100°C. Mucoadhesion studies in vitro showed that the mucoadhesive properties increased significantly with increasing thickness of the IPN layer. The inserts were tested for drug release in vitro, and for drug release and retention in rabbit eyes. The presence of IPN, as well as of NaCl, in general increased the drug release rate. The PMA-grafted devices released OXT at lower rates when compared with the PAA-grafted ones. A nearly zero-order release rate for about 1 week was observed in vitro for some types of inserts. When tested in rabbits, some IPN-grafted inserts maintained in the lacrimal fluid a OXT concentration of 20–30 μg/ml for several days: the in vitro minimum inhibitory concentration values (MIC 90%) of OXT against micro-organisms responsible of common ocular infections range from 0.8 to 2.0 μg/ml, while MIC 90% values in the range 14-50 μg/ml have been indicated for Pseudomonas aeruginosa. The ocular retention of IPN-grafted samples was significantly higher with respect to ungrafted ones. The presently described mucoadhesive silicone inserts might prove efficient therapeutic systems for chemotherapy of ocular bacterial infections, such as trachoma.