New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients. Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field. Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-02T16:09:36Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO PARA DEPÓSITO_AMANDA DAMASCENO LEÃO.pdf: 4254308 bytes, checksum: 37ca5d3f981b6ef7d24669240e08a3cc (MD5) / Made available in DSpace on 2017-03-02T16:09:36Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO PARA DEPÓSITO_AMANDA DAMASCENO LEÃO.pdf: 4254308 bytes, checksum: 37ca5d3f981b6ef7d24669240e08a3cc (MD5) Previous issue date: 2016-03-03 / CNPq / Hidróxidos duplos lamelares são materiais inorgânicos, estruturados bidimensionalmente, dotados de carga elétrica e com capacidade de interagir e carrear moléculas orgânicas. Proporcionam aumento de solubilidade, estabilidade e alteração na liberação da molécula intercalada ou adsorvida. A presente dissertação objetivou o aumento da taxa de dissolução aquosa do hipoglicemiante glibenclamida utilizada no tratamento do diabetes mellitus tipo II, para tanto realizou-se a adsorção do fármaco em HDLs do tipo Mg2Al(OH)8(Cl).nH2O e Zn2Al(OH)8(Cl).nH2O. Os sistemas foram obtidos através de síntese por co-precipitação e caracterizados pelas técnicas: análise elementar; difratometria de raios X; espectroscopia na região do infravermelho (FTIR), microscopia eletrônica de varredura (MEV) e calorimetria exploratória diferencial (TGA-DSC) acoplada à espectrometria de massa (MS). O percentual de glibenclamida nos sistemas segundo a análise elementar foi de 25,23% para Mg2Al(OH)8(Cl).nH2O e de 26,85% para Zn2Al(OH)8(Cl).nH2O, observou-se retardamento de 130°C na decomposição do fármaco em Zn2Al(OH)8(Cl).nH2O e alteração na estrutura cristalina em ambos os sistemas. Para a avaliação das alterações do perfil de dissolução, os sistemas foram submetidos ao teste de dissolução usando meio ácido com pH 1,2 e meio básico com pH 7,3, no qual, foi observado o aumento de 500% na taxa de dissolução da glibenclamida no HDL Mg2Al(OH)8(Cl).nH2O e de 300% na taxa de dissolução de Zn2Al(OH)8(Cl).nH2O em meio básico. Assim, pode-se concluir que os novos sistemas obtidos apresentaram aumento significativo da taxa de dissolução da glibenclamida podendo portanto, ser considerados como promissores para aplicações tecnológicas futuras. / HDLs are inorganic materials, two-dimensionally structured, equipped with electric charge and the ability to interact and caries organic molecules. Provide increased solubility, stability and change in the release of the intercalated or adsorbed molecule. This work aimed to increase the aqueous solubility of hypoglycemic glibenclamide, used in the treatment of diabetes mellitus type II, for both held the adsorption of the drug in the HDLs type Mg2Al(OH)8(Cl).nH2O and Zn2Al(OH)8(Cl).nH2O. The systems were obtained through synthesis by co-precipitation and characterized by the techniques: elemental analysis; X-ray diffraction; scanning electron microscopy (SEM); in the infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC-TGA) coupled with mass spectrometry (MS). The loading of the glibenclamide in the systems according to the elemental analysis was 25.23% for Mg2Al(OH)8(Cl).nH2O and 26.85% for Zn2Al(OH)8Cl.nH2O, the retardation was observed 130° C the decomposition of the drug in Zn2Al(OH)8(Cl).nH2O and also to change the crystalline structure of both systems. For the evaluation of the change of the dissolution profile systems were subjected to the dissolution test using pH 1.2 with acidic and basic medium at pH 7.3, which showed an increase of 100% in the solubility of glibenclamide in LDH Mg2Al (OH)8(Cl).nH2O and 60% Zn2Al (OH)8(Cl).nH2O. Thus, one may conclude that the obtained new systems have provided substantial increase of the solubility of glibenclamide and can therefore be considered promising for future technological applications.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-07T13:13:13Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO DAYANNE.pdf: 3522857 bytes, checksum: cf44960151386725475547d266f32f30 (MD5) / Made available in DSpace on 2017-03-07T13:13:13Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO DAYANNE.pdf: 3522857 bytes, checksum: cf44960151386725475547d266f32f30 (MD5) Previous issue date: 2016-03-04 / CAPES / O Tamoxifeno (TMX) utilizado no tratamento do câncer de mama, apresenta diversas desvantagens, elevada toxicidade, baixa solubilidade e precipitação no ambiente gástrico na forma de sal com aumento do risco de ocorrência de câncer de estômago. Os sistemas de dispersões sólidas (DS) têm sido utilizados com polímeros comerciais, Eudragit®, para liberação controlada e em determinados pH. Assim, o objetivo desse estudo foi desenvolver sistemas de dispersões sólidas para liberação pH dependente do tamoxifeno. Utilizou-se os polímeros Eudragit® RL 100, Eudragit® L 100 e TMX, pelo método de evaporação do solvente, obtendo DS10%, 20%, 30%, 40%, 50% e 60%, mistura física MF30% e dispersões binárias (DS binária) sem fármaco. A difração de Raios-X (DRX) mostrou amorfização das dispersões formadas nas proporções de 10%, 20%, 30%, 40%, 50% e 60%. Na MF30% foi constatada a cristalinidade do fármaco. Na análise térmica através das curvas (TG), foi observada aumento da temperatura de decomposição da DS binária. No DSC, para a MF30% foi observado o pico de fusão e as etapas de decomposição do fármaco. Já nas DS10%, DS20% e DS30% observou-se ausência desses picos. Para a DS binária a temperatura de transição vítrea (Tg) se assemelhou a Tg do Eudragit® L 100, aumentando estabilidade das DS. Na espectroscopia de Infravermelho (FTIR) foi verificado interações polímero-polímero através da diminuição e alargamento das bandas de 2601 cm-¹, atribuído ao grupamento livre do ácido carboxílico do Eudragit® L 100. Observou interação fármaco-polímero com ausência dos picos característicos do fármaco nas regiões de 1588 cm-¹, referente ao amônio quaternário, nas DS 10% e DS 20%, e diminuição da intensidade das bandas na DS 30%. Assim com o alargamento de banda das regiões 2601cm-1 do Eudragit® L100, sugerindo a interação do fármaco nessa região. A Microscopia Eletrônica de Varredura exibiu diferenças significativas nas dispersões sólidas DS30% e MF 30%. Para os testes de solubilidade nos meios pH 1,2 e 7,4 a solubilidade do TMX aumentou com a diminuição do pH já com adição de Tween80 no meio pH 7,4 a solubilidade do fármaco aumentou em até 26 vezes a concentração, melhorando a solubilidade do TMX nesse meio. As condições designadas na USP para formulação gastrorresistentes (pH 1,2) foram satisfatórias para as DS10% e DS20%. Porém, para DS30% a condição não foi alcançada devido a mudanças da permeabilidade do polímero, pela formação de iPECS. No pH 7,4 + Tween80 (0,4% p/v) houve controle na liberação do fármaco com aumento de solubilidade de até 200% para DS20% e Ds30%. Portanto, pode-se concluir que o método empregado foi eficaz na obtenção das dispersões com aumento da estabilidade do fármaco nos sistemas formados, atendendo as diretrizes da USP para formulações gastrorresistentes e liberando de forma modificada o fármaco no pH 7,4, com incremento solubilidade. Sendo um promissor sistema para futuras modificações e estudos. / Tamoxifen (TMX) used in the treatment of breast cancer, has several disadvantages, like high toxicity, low solubility and precipitation in the gastric environment in salt form with an increased risk of stomach cancer. Solid dispersions systems (DS) have been used with commercial polymers, Eudragit, for controlled release and certain pH. The aim of this study was to develop solid dispersion systems for pH dependent release of tamoxifen. It was used the polymers Eudragit RL 100, Eudragit L 100 and TMX, the solvent evaporation method, obtaining. DS10%, 20%, 30%, 40%, 50% and 60% physical mixture and binary dispersions PM30% (binary DS) no drug. The X-ray diffraction (XRD) showed amorphization of the dispersions formed in proportions of 10%, 20%, 30%, 40%, 50% and 60%. In PM30% was observed crystallinity of the drug. In the thermal analysis curves through (Tg), it was observed increase of the decomposition temperature of the binary DS. In DSC, for PM30% was observed melting peak of the drug and decomposition steps. Already in DS10%, DS20 and DS30% was observed the absence of these peaks. For binary DS glass transition temperature (Tg) resembled the Tg of Eudragit® L 100, increasing stability of the DS. In infrared spectroscopy (FTIR) was checked polymer-polymer interactions by lowering and widening of the bands 2601 cm-¹ assigned to the free carboxylic acid grouping of Eudragit® L 100 observed drug-polymer interaction with the absence of the characteristic peaks drug in the region of 1588 cm-¹, referring to quaternary ammonium, and the DS 10% DS 20%, and decreased intensity of the bands in DS30%. So, with the extension band of regions 2601cm-1 Eudragit® L100, suggesting the interaction of the drug in this region. The Scanning Electron Microscopy showed significant differences in solid dispersions DS30% and 30% MF. For solubility testing in pH 1.2 and 7.4 means the solubility of TMX increased with decreasing pH already with addition of Tween 80 at pH 7.4 means the solubility of the drug increased up to 26 times the concentration by improving TMX solubility in this medium. The conditions referred to in USP gastroresistant formulation (pH 1.2) were satisfactory for DS10 and DS20%. However, in DS30%, the condition was not achieved due to the polymer permeability changes by forming iPECS. At pH 7.4 + Tween 80 (0,4 w/v) there has been control drug release with increased solubility up to 200% for DS20 and DS30%%. Therefore, it can be concluded that the method employed was effective in obtaining the dispersions with increased drug stability in the systems formed, meeting the USP guidelines for gastroresistant formulations and modifying the release of the drug at pH 7.4, with increased solubility; and that it is a promising system for future modifications and studies.

Magister Pharmaceuticae - MPharm / Sutherlandia frutescens is a traditional plant medicine widely used in South Africa. Traditionally, the leaves of S. frutescens are mainly used as a tea, but these traditional dosage forms have several disadvantages, including that they are not particularly convenient to prepare and store, encourage dosage inaccuracy and are highly susceptible to microbial contamination. To solve these problems, dried aqueous extract forms, e.g. freeze dried aqueous extract (FDAE) of S. frutescens were prepared, but they, in turn, may still suffer from instability and contain mainly hydrophilic phytoconstituents that are poorly absorbed and delivered for in vivo activity. Modified forms of the FDAE, i.e. the active phytopharmaceutical ingredient (API), may be a better solution. Therefore this study sought to prepare liposomes and phytosomes of the freeze dried aqueous extract of Sutherlandia frutescens, as a means of increasing the total the surface area of the API, thus improving its release and dissolution in gastrointestinal fluids. Liposomes and phytosomes of the FDAE of Sutherlandia frutescens obtained were prepared using a thin film hydration method at ratios of lecithin: S. frutescens (3:1) and phosphatidylcholine: S. frutescens (2:1) respectively. The physical characteristics (i.e. particle size, size distribution, zeta potential, and morphology), of flavonoid glycosides (i.e. sutherlandins A to D; API) as well as content and release profiles of each dosage form (i.e. FDAE liposome or phytosomes) at pH 1.2 and pH 6.8 was determined. A validated HPLC assay was used to determine and compare the flavonoid glycoside content and release profiles of the liposomes and phytosomes. Both liposomes and phytosomes were successfully prepared, in moderate yields (± 30 %, and ± 50 %, respectively), using the thin film hydration method. The liposomes had a significantly smaller size, lower size distribution, higher zeta potential and better stability than the phytosomes (p < 0.05). The phytosomes, however, had significantly higher flavonoid glycoside encapsulation efficiency than the liposomes (±50 % vs ±26 %; p < 0.01). In addition, the release at 120 minutes, of flavonoid glycosides from the liposomes (63%, 58%, 76% and 46% % at pH 1.2, and 78%, 76%, 87% and 89 % at pH 6.8 for sutherlandins A, B, C and D, respectively) was significantly higher and faster than that of the phytosomes (52%, 41%, 51% and 39 % at pH 1.2, and 31% 31%, 33%and 45% % at pH 6.8, for sutherlandins A, B, C and D, respectively). The differences in release were likely due to differences in particle size and size distribution of the two modified API forms. Overall, liposomes and phytosomes can be considered promising vehicles for delayed delivery of herbal crude extracts. Based on its characteristics (i.e. narrower size distribution, and better stability), the liposomes were preferred compared to the phytosomes offering a better kinetic release profile. The phytosomes had higher encapsulation than the liposomes that may be due to complex formation between the API and the lipid.

Mini-matrix multiple unit dosage forms (MUDFs) of diclofenac sodium and S(+) ibuprofen have been prepared. Normal tabletting techniques were used to form the mini-matrices prior to their enclosure in hard gelatin capsules. Four natural hydrophilic gums, namely xanthan, karaya, locust bean and carrageenan gums as well as hydroxypropyl methylcellulose (HPMC) were used as the principle release-retarding agents. Various excipients - lactose, Encompress®, cellulose acetate phthalate (CAP), Veegum F® and Avicel PH101® - were added in different proportions to further modify drug release. The diclofenac sodium mini-matrices (4.5 mm in diameter) were produced by the wet granulation method. The release profiles from several encapsulated minimatrices in phosphate buffer solution (pH 7.0) showed that xanthan, karaya and locust bean gums could sustain the release of diclofenac sodium while the carrageenan gum did not produce a satisfactory sustaining effect. The rank order of decreasing swelling rate in both axial and radial dimensions was xanthan > karaya > locust bean gum and each of these gums showed almost Fickian swelling behaviour. The solvent penetration rates were consistent with the swelling rates. However, the order of decreasing drug release and erosion rates was locust bean> xanthan > karaya gum. For each of these gums, the release behaviour was anomalous indicating that both Fickian drug diffusion and polymer relaxation were involved in the release process. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution period. The study involving xanthan gum showed that the diclofenac sodium release rate declined linearly with a progressive increase in the gumcontent, without changing the release behaviour. However, for high drug: xanthan gum ratio (2:1), the release kinetics changed to Super Case II. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. Mini-matrices containing HPMC produced faster drug release than those containing the three natural gums. There was no synergistic effect between xanthan and locust bean gums on the release of diclofenac sodium from mini-matrices. Variation in the stirring speed (used in the dissolution apparatus) and matrix volume had little effect on drug release, whereas the pH of the dissolution medium greatly affected the release of diclofenac sodium. Following on from the studies involving diclofenac sodium, xanthan and karaya gums were used to produce mini-matrices of S(+) ibuprofen. Excipients with good compressibility characteristics such as lactose, Encompress® and Avicel PH101® were needed in the formulations. At pH 7, higher drug release rates were obtained with karaya gum (Super Case II mechanism) compared with xanthan gum (anomalous behaviour). Solubility differences between the excipients slightly affected the release rate. Compression forces (11 - 26 kN) slightly affected the crushing strength. The minimatrices were relatively stable to variation in temperature (5 - 37°C) and relative humidity (10 - 75%) over a 2 month time period. These studies have shown that near zero-order release of diclofenac sodium and S(+) ibuprofen can be achieved using encapsulated mini-matrices formulations. The release mechanisms and release rates can be adjusted by variation of the type and content of gums and/or excipients.

No description available.

No / The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model.

L’électrospinning est un procédé couramment utilisé pour la fabrication de membranes nanofibreuses non-tissées. Ces membranes sont particulièrement intéressantes pour des applications tels que l’ingénierie tissulaire et la libération contrôlée de médicaments car elles sont très poreuses et ont une large surface spécifique. Dans une première partie, nous avons développé une nouvelle stratégie afin de contrôler la morphologie et la dimension des fibres fabriquées par electrospinning. Puis nous avons développé un composite fait de nanofibres de PLA et de microparticules de PEG auto-organisé, créant des motifs en nid d’abeilles qui grandissent avec l’épaisseur de la membrane. Ces membranes auto-organisées ont une structure poreuse dont la dimension des pores va de quelques microns à plusieurs centaines de microns. Enfin, deux modèles ont été développés pour une libération contrôlée d’un composé model : la délivrance retardée par l’élaboration de structure sandwich et la libération directionnnelle par la création d’un gradient de concentration avec différentes cinétiques. / Electrospinning is widely used for the synthesis of nanofibrous non-woven membranes. The fabricated electrospun membranes have high porosity and high surface to volume ratio; they are thus suitable for many applications such as sensing, tissue engineering or drug delivery. In the present work, the first focus was on the fabrication of electrospun fibers with controlled morphology and dimension. Then A self-organized honeycomb-like composite made of simultaneously electrosprayed PEG microparticles and PLA electrospun fibers was developed. The obtained composite mat exhibits a hierarchical, porous structure with pore sizes ranging from few microns up to several hundreds of microns. Finally, a method tailoring the hydrophobicity of drug loaded nanofibrous membranes by the incorporation of electrosprayed PEG microparticles was developed.

In this study, it is aimed to develop an injectable controlled release system of PCL and P(L,DL)LA microspheres loaded with TA and/or Ral for local treatment of rheumatoid arthritis which will avoid from systemic side effects of traditional administration and eliminate problems caused by direct local injections. Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder that most commonly causes inflammation and tissue damage in joints and tendon sheaths. Current strategies for the disease are mainly towards relieving symptoms and increasing mobility. The microsphere form drug delivery systems were developed to enhance the treatment success of rheumatic diseases by providing these agents alone or together for long terms without causing systemic or local site effects upon injection to the RA joints. Microspheres were prepared with s/o/w solvent evaporation technique and optimized to achieve a suitable size for joint application, to sustain the delivery of the drug(s), to provide required amount of the agent with feasible amount of microsphere. In order to manage these, microspheres prepared with different combinations of polymers and drugs were examined for particle size analysis, surface and structural characterizations, time related drug release properties, and drug loading capacities. In vitro cytotoxicity tests using 3T3 fibroblast cells were done to evaluate the biocompatibility of drug loaded PCL microspheres. The degradation of polymers were conducted and evaluated by GPC analysis. In PCL:TA microspheres, as polymer:drug ratio decreased (from 10:1 towards 10:4), namely as the drug partition increased, it was seen that encapsulation efficiency and loading percentages increased. Meanwhile, percent release of the drug decreased, indicating more prolonged release. Among all microspheres, PCL:TA 10:4 and PCL:Ral 10:2 were found to be the most appropriate for dual release in terms of release values (ca 21% and 0.09%, respectively), loadings (ca 27% and ca 13%, respectively) and mean particle size values (ca 100 &mu / m and ca 95 &mu / m, respectively). After release studies, microspheres preserved their sphericity. These selected polymer:drug groups also represented no cytotoxic effect. The microspheres for dual drug study (PCL:TA:Ral 10:4:2) released app. 55% of its TA and 0.29% of Ral at the end of 4 weeks. Drug loading capacities of these microspheres were found to be ca 14% for TA and 8% for Ral. Furthermore, with dual loading case, smallest mean particle size (68 &mu / m) could be obtained among all studied groups. P(L,DL)LA microspheres caused high viscosity problems during microsphere preparation steps and resulted in the slowest release, which was unfavorable for the aim of the study. To our knowledge there is no microsphere study reported with P(L,DL)LA in literature. The TA and Ral delivery systems with PCL and P(L,DL)LA were developed and studied for the first time in literature and they were optimized for RA treatment purposes. The potential of these systems, should be further tested in experimental animal models of RA.

Chronic diseases can often be managed by constantly delivering therapeutic amounts of drug for prolonged periods. A controlled release for extended duration would replace the need for multiple and frequent dosing. Local drug release would provide added benefit as a lower dose of drug at the target site will be needed as opposed to higher doses required by whole body administration. This would provide maximum efficacy with minimum side effects. Nonetheless, a problem with the known implantable drug delivery devices is that the delivery rate cannot be controlled, which leads to drug being released in an unpredictable pattern resulting in poor therapeutic management of patients. This dissertation is the result of development of an implantable drug delivery system that is capable of long-term zero order local release of drugs. The device can be optimized to deliver any pharmaceutical agent for any time period up to several years maintaining a controlled and desired rate. Initially significant efforts were dedicated to the characterization, biocompatibility, and loading capacity of nanoporous metal surfaces for controlled release of drugs. The physical characterization of the nanoporous wafers using Scanning electron microscropy (SEM) and atomic force microscopy techniques (AFM) yielded 3.55 x 10⁴ nm³ of pore volume / μm² of wafer surface. In vitro drug release study using 2 - octyl cyanoacrylate and methyl orange as the polymer-drug matrix was conducted and after 7 days, 88.1 ± 5.0 % drug was released. However, the initial goal to achieve zero order drug release rates for long periods of time was not achieved. The search for a better delivery system led to the design of a perforated microtube. The delivery system was designed and appropriate dimensions for the device size and hole size were estimated. Polyimide microtubes in different sizes (125-1000 μm) were used. Micro holes with dimensions ranging from 20-600 μm were fabricated on these tubes using photolithography, laser drilling, or manual drilling procedures. Small molecules such as crystal violet, prednisolone, and ethinyl estradiol were successfully loaded inside the tubes in powder or solution using manual filling or capillary filling methods. A drug loading of 0.05 – 5.40 mg was achieved depending on the tube size and the drug filling method used. The delivery system in different dimensions was characterized by performing in vitro release studies in phosphate buffered saline (pH 7.1-7.4) and in vitreous humor from the rabbit’s eye at 37.0 ± 1.0°C for up to four weeks. The number of holes was varied between 1 and 3. The tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE). Linear release rates with R²>0.9900 were obtained for all groups with CV and EE. Release rates of 7.8±2.5, 16.2±5.5, and 22.5±6.0 ng/day for CV and 30.1±5.8 ng/day for EE were obtained for small tubes (30 μm hole diameter; 125 μm tube diameter). For large tubes (362-542 μm hole diameter; 1000 μm tube diameter), a release rate of 10.8±4.1, 15.8±4.8 and 22.1±6.7 μg/day was observed in vitro in PBS and a release rate of 5.8±1.8 μg/day was observed ex vivo in vitreous humor. The delivery system was also evaluated for its ability to produce a biologically significant amounts in cells stably transfected with an estrogen receptor/luciferase construct (T47D-KBluc cells). These cells are engineered to produce a constant luminescent signal in proportion to drug exposure. The average luminescence of 1144.8±153.8 and 1219.9±127.7 RLU/day, (RLU = Relative Luminescence Units), yet again indicating the capability of the device for long-term zero order release. The polyimide device was characterized for biocompatibility. An automated goniometer was used to determine the contact angle for the device, which was found to be 63.7±3.7degreees indicating that it is hydrophilic and favors cell attachment. In addition, after 72 h incubation with mammalian cells (RAW 267.4), a high cell distribution was observed on the device’s surface. The polyimide tubes were also investigated for any signs of inflammation using inflammatory markers, TNF-α and IL-1β. No significant levels of either TNF-α or IL-1β were detected in polyimide device. The results indicated that polyimide tubes were biocompatible and did not produce an inflammatory response. / text