This paper presents the fabrication of controlled release devices for anticancer drug paclitaxel using supercritical antisolvent method. The thermodynamic and hydrodynamic effects during supercritical antisolvent process on the particle properties obtained were investigated. Scanning electron microscopy was employed to study particle sizes and morphologies achieved. It was observed that increasing supercritical pressure improves the surface morphology of particles obtained, and increasing the flow rate of the organic solution jet reduces the particle sizes obtained. A modified Supercritical Antisolvent with Enhanced Mass transfer setup was developed to produce monodispersed nanoparticles with high recovery yield. High performance liquid chromatography was used to determine the encapsulation efficiency and in vitro release profiles of paclitaxel loaded particles obtained. The encapsulation efficiencies of particles obtained using the modified SASEM process were high and up to 83.5%, and sustained release of paclitaxel from the polymer matrix was observed over 36 days release. The thermogram properties of the particles were also analyzed using differential scanning calorimetry to determine the crystalline state of polymer and drug. / Singapore-MIT Alliance (SMA)

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting an estimated 1% of the global population. Joint protection is one intervention with some quality evidence of efficacy for RA self-management. However, joint protection education is often provided only in urban centres during Arthritis Self-Management Programs (ASMPs) in classroom sessions at designated times. These programs, therefore, may not be available to all who need them. Providing and testing more accessible methods of delivering joint protection education to people living with RA may improve accessibility. Aims: (i) To develop a virtual world (VW) intervention available via the Internet in Second Life®, that aims to improve the knowledge of joint protection among people with RA and (ii) to undertake a pilot randomised controlled trial (RCT) to assess the feasibility of conducting a subsequent large scale RCT. Methods: First, qualitative interviews with occupational therapists and clients living with RA who had previous experiences teaching or taking arthritis self-management programmes were undertaken and thematically analysed. This analysis informed the design of the VW joint protection education intervention. Second, the intervention was constructed and tested with these same participants. Their feedback helped refine the VW intervention and select assessment tools for the pilot RCT. Third, in a pilot RCT, three primary methods of advertising and invitation were used to recruit subjects: (i) poster invitations with take-home paper copies from clinical settings; (ii) direct messages to Twitter® users living with RA; and (iii) online discussion forums. Participants were recruited after contacting the principal investigator, reading an invitation letter and giving written informed consent. Participants were randomised to intervention or (30-day) waiting list control group, and completed a series of measures. These were completed after 30 days of program access for the treatment group and on enrolment in the study for the control group. Survey completion was online and included piloted knowledge-based questions about joint protection, validated during the second phase of the study with occupational therapists who were experts in joint protection education. A higher score was indicative of better joint protection knowledge. Standardized measures used on the survey included the Arthritis Impact Measurement Scale, Short Form, version II (AIMS2SF) and Pain Self-Efficacy Questionnaire (PSEQ). Results: It was possible to develop a VW education program focused on RA and joint protection based on the content identified by participants in the first part of the study and test with the tools selected. The program developed included input from client users, following the theorectical basis of occupational therapy as a client-centred practice. Additionally, the program developed applied principles of adult-learning and the recommendations of existing programs regarding chronic disease management. Recruitment of 50 participants for the pilot RCT was challenging, taking 6 months with low response rates for all three methods. The poorest response rates were to poster and paper invitations in clinical settings. The most effective means of recruitment was via electronic bulletin boards, such as blogs. All subjects, once randomised to the control or intervention group completed the online questionnaire. However, adherence to the intervention was poor; only 15 out of 25 randomised reported using the program. On the other hand, all 15 who used the program indicated that this medium was acceptable to learn about joint protection, despite 5/15 of these subjects reporting some difficulty accessing the program. All participants completed the three questionnaires (knowledge, impact, pain self-efficacy) and these may be useful in a definitive RCT. Although the main purpose of using Intention to Treat Analysis in pilot studies is to practice and check that analysis is feasible, there was a positive statistically significant difference between the treatment (x̄=52.8%) and control (x̄=24%) group scores on a test of joint protection knowledge using an independent samples t-test (F value, 20.8 p < 0.05) comparing joint protection knowledge scores after the treatment group had access to the program for 30 days. A higher score was indicative of better joint protection knowledge. The difference between the two groups was considerable, with the intervention group score mean being more than double that of the control group. Given the magnitude of this difference between groups, a smaller difference between groups would also be worth finding. The difference between groups for the AIMS2SF and PSEQ were not statistically significant using an independent samples t-test (F values, 0.5 and 0.2) but there was some suggestion that the intervention group scored more favourably on some of the subscales more relevant to joint protection on both the AIMS2SF and PSEQ, particularly noteworthy was a higher score pertaining to ability to carry out work on both measures. In a definitive trial a sample size of 1250 participants would give 80% power to find a difference of 28.8% on joint protection knowledge, weighted score of 1.8 on the AIMS2SF and overall score of 1.8 on the PSEQ at 5% level of significance. Smaller samples would be required if the PSEQ was dropped as a measure in a future study. Sample sizes of 14 and 558 would be required for the joint protection knowledge and AIMS2SF respectively at the same level of power and significance. Conclusion: A VW intervention to improve joint protection knowledge has been developed and is worth testing further. The intellectual contribution of the creation of this program using this methodology is that an occupational therapy based study using client input and priniciples of adult learning to create the intervention has been conducted, applying client-centred practice in research, which is, in reality, present in a minority of studies at this time. A full RCT would be feasible, though very challenging, given the numbers of subjects required for recruitment, most likely recruiting via the Internet on relevant RA focus sites, such as RA bloggers, and using the same outcome measures as in this study. A sample size of 1250 could feasibly be recruited in 36 months if a full time study were undertaken with suggestions discussed to assist with future study recruitment. However, given the number of study dropouts at enrolment seen in this study, close to double this number would be needed, entailing a recruitment period of up to 72 months, or 6 years, making a full RCT less practical. A future study may need to consider either a longer enrolment period, different outcome measures as well as address the limitations of this study, including the limited time of enrolment in this pilot RCT. However, longer enrolment duration would increase the amount of time required for a future full RCT, reducing the feasibility of a future study. Findings from this study indicate that the program developed would likely to be useful to people who are not able to access the urban centred classroom based program. On the other hand, those participants who used the program incurred no costs, appeared to have no risks or detrimental impact with possible improvement in knowledge and self-efficacy. Now the intervention has been developed, refinement, maintenance, and use is low cost for service providers, so it could be used routinely now for those who prefer it to ASMPs with an ongoing preference trial.

Hypertonic saline (HS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The first study compared the behavioral and cognitive consequences of HS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HS, or 0.9% saline vehicle (1.0 mL/kg) were given at 2, 24, and 48 hrs post-CCI. Behavioral results revealed that animals treated with NAM and HS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 18-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HS animals showed no acquisition of this task. Histological examinations revealed that the HS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HS without this associated tissue loss. Study 1 suggested that future research into HS should include drug injection time course studies. Multiple injections may be responsible for the notable tissue damage. Therefore, it is possible that fewer injections will result in comparable behavioral recovery and less tissue damage that was observed. Due to the detrimental effects of 7.5% HS on cognition and hippocampal tissue following multiple administration in study 1, the proposed second study sought to study the behavioral and cognitive effects of HS using either single or multiple injection regime. The proposed study entailed a lengthier testing schedule than in study 1 and included the same histological examination to compare the different dosages. Additionally, edema formation was measured 24 hours following each drug endpoint in order to delineate the possible underlying mechanism of the observed deficits. In Study 2, HS tended to improve function on motor, sensorimotor and neurological tasks. Although this was a trend on all tests, animals treated with a single administration of HS overall performed better on all tasks compared to those receiving double or multiple injections. In the retrograde amnesia test, although not significant, the Sham, HS-2, and HS-24 animals showed improvement; whereas, the Vehicle and HS-48 animals showed no improvement in performance. This could possibly be linked to the additional hippocampal tissue loss that was noted in the HS-48 animals. In the working memory paradigm, the HS-2 and Vehicle groups had longer latencies to reach the platform than did the Sham group. However, after the first testing day, there were no significant differences between any of the groups. All animals treated with HS performed at the same rate and their performance either stayed the same over the three day testing period or became worse. It appears these animals were unable to learn and improve in the new memory acquisition task which is comparable to the results found in study 1. In study 1, there were again no observed hippocampal volume differences between the Sham and Vehicle-treated animals. However, there was extensive hippocampal tissue damage observed in all of the HS groups. Furthermore, animals treated with a single administration of HS had less hippocampal loss than those with double or multiple doses. Those animals receiving more than one dose of HS lost significantly more hippocampal tissue than the Vehicle group. The results of study 2 are comparable, and support, the results of study 1. Both studies support the strengths and weakness of HS therapy following TBI. Although there are potential benefits of HS therapy, there are also detrimental risks involved. Cognitive and structural damage could possible occur if the dosage amounts are not closely studied and monitored. Although the use of HS may be beneficial to reduce ICP following TBI, it appears that the use of HS may also lead to direct or indirect tissue loss possibly by chronic cellular dehydration. Stronger or more delineated effects may be noticed using higher doses or concentrations of HS in future studies. However, due to the nature of these results, caution should be advised with the use of all therapeutic usage of HS until further detailed studies are conducted.

PURPOSE: Develop and evaluate a chart review tool (CRT) to improve the safety and effectiveness of prescribing controlled substances in a primary care setting. METHODS: A Controlled Substance Review Committee, consisting of volunteer primary care physicians and a clinical pharmacist, developed a CRT to assess compliance with a primary care clinic’s controlled substance prescribing policy and effectiveness of therapy. The CRT was based on existing clinic policies and American Pain Society/American Academy of Pain Medicine clinical guidelines for opioid prescribing. Every month, committee physicians used the CRT to review medical records of patients prescribed controlled substances chronically. The CRT tracked factors from the previous 6 months, including morphine equivalent dose (MED) prescribed, indication for treatment, documentation of treatment effectiveness, the Opioid Risk Tool score (ORT score), results from urine drug testing (UDT) and patient violations of the clinic’s controlled substance policy. These findings are used to provide the treating physician constructive, non-punitive feedback. We also assessed if the use of the CRT resulted in change in MED prescribed. RESULTS: Ninety-nine patient charts from 14 different physicians were reviewed over 1 year. Eighty-eight of these patients were receiving opioids for chronic pain, with an average dose in MED 72.6 mg/day (SD 89). Twenty-nine percent of charts had documentation that the controlled substance was improving the patient’s quality of life or decreasing their pain. Sixty percent of patients had at least one violation of the clinic’s controlled substance treatment agreement in the prior 6 months, and half of the violations were due to missed appointments with specialists to help manage pain. Patients were more likely to have a violation of controlled substance policy in the past 6 months if they were prescribed both a benzodiazepine (BZD) and an opioid (p=0.04), had a documented treatment agreement (p=0.002), or were high risk per ORT score (p=0.001). The mean dose of opioids, for the 88 patients who were prescribed opioids, decreased 2.6 mg/day MED from time of chart review until the end of study (mean duration 6.3 months), compared to a 6.9 mg/day MED increase that occurred from 12 months prior to chart review to the time of chart review (p=0.01). CONCLUSION: Development and implementation of a CRT in an urban primary care clinic provided helpful insight on prescribing practices, and has promise to improve quality of opioid prescribing. The most common violation of the clinic policy was missed appointments with specialists, and patients prescribed both BZD and an opioid or were high risk per ORT were most likely to have violations. Documentation of effectiveness of therapy was lacking.

abstract: Mesoporous materials that possess large surface area, tunable pore size, and ordered structures are attractive features for many applications such as adsorption, protein separation, enzyme encapsulation and drug delivery as these materials can be tailored to host different guest molecules. Films provide a model system to understand how the pore orientation impacts the potential for loading and release of selectively sized molecules. This research work aims to develop structure-property relationships to understand how pore size, geometry, and surface hydrophobicity influence the loading and release of drug molecules. In this study, the pore size is systematically varied by incorporating pore-swelling agent of polystyrene oligomers (hPS) to soft templated mesoporous carbon films fabricated by cooperative assembly of poly(styrene-block-ethylene oxide) (SEO) with phenolic resin. To examine the impact of morphology, different compositions of amphiphilic triblock copolymer templates, poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO), are used to form two-dimensional hexagonal and cubic mesostructures. Lastly, the carbonization temperature provides a handle to tune the hydrophobicity of the film. These mesoporous films are then utilized to understand the uptake and release of a model drug Mitoxantrone dihydrochloride from nanostructured materials. The largest pore size (6nm) mesoporous carbon based on SEO exhibits the largest uptake (3.5&mu;g/cm2); this is attributed to presence of larger internal volume compared to the other two films. In terms of release, a controlled response is observed for all films with the highest release for the 2nm cubic film (1.45 &mu;g/cm2) after 15 days, but this is only 56 % of the drug loaded. Additionally, the surface hydrophobicity impacts the fraction of drug release with a decrease from 78% to 43%, as the films become more hydrophobic when carbonized at higher temperatures. This work provides a model system to understand how pore morphology, size and chemistry influence the drug loading and release for potential implant applications. / Dissertation/Thesis / M.S. Chemical Engineering 2011

Catalisadores Ziegler-Natta (Z-N) de 4ª geração são preparados com suporte de dicloreto de magnésio com morfologia controlada, obtidos a partir de adutos etanólicos de dicloreto de magnésio (MgCl2.nEtOH). O objetivo deste trabalho foi otimizar o balanço entre as variáveis independentes concentração de reagentes, velocidade de agitação da emulsão e pressão de transferência, na preparação do aduto com controle morfológico. Os adutos etanólicos com controle da morfologia esférica foram preparados pela transferência controlada do aduto fundido a 125 ºC e precipitação por resfriamento brusco (quenching) em não-solvente a – 50 ºC, utilizando o método Controlled Turbulence Emulsion Method (CTEM). A ativação do MgCl2.nEtOH foi feita pela rota química para remoção do etanol e consequente aumento da área superficial do suporte. Os adutos foram preparados com razão molar EtOH/MgCl2 de 3,5 ou 63% (p/p) de etanol. Os experimentos foram realizados segundo planejamento fatorial 23 a dois níveis e ponto central replicado. As variáveis dependentes foram o diâmetro médio e distribuição de tamanho das partículas do suporte, densidade aparente compactada, morfologia e teor de álcool incorporado no aduto. Os catalisadores Z-N’s foram obtidos a partir dos suportes tratados com TiCl4 e um doador de elétrons interno, e testados em polimerização padrão de propileno. Foi observado que o controle do tamanho (diâmetro médio) da partícula do suporte é altamente dependente da velocidade de transferência, controlada pela pressão no reator de fusão. A concentração do reagente ([MgCl2]) teve efeito significativo nas quatro variáveis dependentes. A velocidade de agitação no reator de fusão ou da emulsão do aduto fundido teve efeito significativo somente na morfologia do suporte, sendo este efeito menor que o observado para a pressão de transferência. A velocidade de agitação não teve significância no processo de transferência CTEM, sendo este mais suscetível a variação da pressão no reator. / 4th Generation Ziegler-Natta catalysts (Z-N catalysts) are prepared with magnesium dichloride support with controlled morphology, obtained from ethanolic adducts of magnesium dichloride (MgCl2.nEtOH). The objective of this work was to optimize the balance between the independent variables reagent concentration, emulsion agitation speed and transfer pressure, in the preparation of the adduct with morphological control. The ethanolic adducts with spherical morphology control were prepared by controlled transfer of the molten adduct at 125 °C and quenching in nonsolvent at - 50 °C using the Controlled Turbulence Emulsion Method (CTEM). The activation of MgCl2.nEtOH was done by chemical route to remove the ethanol and consequently increase the surface area of the support. The adducts were prepared with EtOH/MgCl2 molar ratio of 3.5 or 63% (w/w) ethanol. The experiments were performed according to factorial design 23 at two levels and replicated central point. The dependent variables were the mean diameter and particle size distribution of the carrier, compacted bulk density, morphology and alcohol content incorporated in the adduct. The Z-N’s catalysts were obtained from TiCl4-treated media and an internal electron donor, and tested in standard polypropylene polymerization. It has been observed that size control (median diameter) of the carrier particle is highly dependent on the transfer rate, controlled by the pressure in the fusion reactor. The concentration of the reagent ( [MgCl2] ) had a significant effect on the four dependent variables. The stirring rate in the melt reactor or the cast adduct emulsion had significant effect only on the morphology of the support, this effect being smaller than that observed for the transfer pressure. The stirring speed was not significant in the CTEM transfer process, which is more susceptible to pressure variation in the reactor.

abstract: The present study applied latent class analysis to a family-centered prevention trial in early childhood to identify subgroups of families with differential responsiveness to the Family Check-up (FCU) intervention. The sample included 731 families of 2-year- olds randomized to the FCU or control and followed through age five with yearly follow up assessments (Dishion et al., 2014; Shaw et al., 2015). A two-step mixture model was used to examine whether specific constellations of family characteristics at age 2 (baseline) were related to intervention response at age 3, 4, and 5. The first step empirically identified latent classes of families based on a variety of demographic and adjustment variables selected on the basis of previous research on predictors of response to the FCU and parent training in general, as well as on the clinical observations of FCU implementers. The second step modeled the effect of the FCU on longitudinal change in children's problem behavior in each of the empirically derived latent classes. Results suggested a five-class solution, where a significant intervention effect of moderate-to- large size was observed in one of the five classes. The families within the responsive class were characterized by child neglect, legal problems, and mental health issues. Pairwise comparisons revealed that the intervention effect was significantly greater in this class of families than in two other classes that were generally less at risk for the development of disruptive behavior problems, and post hoc analyses partially supported these results. Thus, results indicated that the FCU was most successful in reducing child problem behavior in the highly distressed group of families. We conclude by discussing the potential practical utility of these results and emphasizing the need for future research to evaluate this approach's predictive accuracy. / Dissertation/Thesis / Masters Thesis Psychology 2016

abstract: Solar energy is leading in renewable energy sources and the aspects surrounding the efforts to harvest light are gaining importance. One such aspect is increasing the light absorption, where heliotropism comes into play. Heliotropism, the ability to track the sun across the sky, can be integrated with solar cells for more efficient photon collection and other optoelectronic systems. Inspired by plants, which optimize incident sunlight in nature, several researchers have made artificial heliotropic and phototropic systems. This project aims to design, synthesize and characterize a material system and evaluate its application in a phototropic system. A gold nanoparticle (Au NP) incorporated poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was synthesized as a photo-thermo-responsive material in our phototropic system. The Au NPs generate heat from the incident via plasmonic resonance to induce a volume phase change of the thermo-responsive hydrogel PNIPAAm. PNIPAAm shrinks or swells at temperature above or below 32°C. Upon irradiation, the Au NP-PNIPAAm micropillar actuates, specifically bending toward the incident light and precisely following the varying incident angle. Swelling ratio tests, bending angle tests with a static incident light and bending tests with varying angles were carried out on hydrogel samples with varying Au NP concentrations. Swelling ratios ranging from 1.45 to 2.9 were recorded for pure hydrogel samples and samples with very low Au NP concentrations. Swelling ratios of 2.41 and 3.37 were calculated for samples with low and high concentrations of Au NPs, respectively. A bending of up to 88° was observed in Au NP-hydrogel pillars with a low Au NP concentration with a 90° incident angle. The light tracking performance was assessed by the slope of the pillar Bending angle (response angle) vs. Incident light angle plot. A slope of 1 indicates ideal tracking with top of the pillar being normal to the incident light, maximizing the photon absorption. Slopes of 0.82 and 0.56 were observed for the low and high Au NP concentration samples. The rapid and precise incident light tracking of our system has shown the promise in phototropic applications. / Dissertation/Thesis / Masters Thesis Materials Science and Engineering 2016

Orientador: Flávio Massone / Banca: Stélio Pacca Loureiro Luna / Banca: Valéria Nobre Leal de Souza Oliva / Banca: André Leguthe Rosa / Banca: Juliana Noda Bechara Belo / Resumo: A anestesia venosa total possui muitas vantagens, não polui ar ambiente, fácil de usar em lugares remotos, estabilidade cardiovascular e boa qualidade de recuperação. O propofol, devido sua farmacologia, é um dos fármacos mais usados em infusões contínuas. Recentes avanços têm acontecido na anestesia venosa total com a utilização de infusões alvo controlada, baseados em simulações farmacodinâmicas e farmacocinéticas dos fármacos em tempo real, inclusive na Medicina Veterinária. Em função disso, pretendeu-se colocar em prática este tipo de anestesia, utilizando-a em cadelas para a realização de cirurgias de ovariosalpingohisterectomia. Para isso foram anestesiadas 20 cadelas, após o consentimento livre e esclarecido dos proprietários. Sendo divididos em dois grupos (GI e GII). Em GI, os animais foram pré-tratados com levomepromazina na dose de 0,5mg/kg IV e anestesiados com propofol por infusão alvo controlada na dose de indução de 3,5æg/ml e na dose de manutenção de 1,5 æg/ml IV, através bomba de infusão Harvard pump, associado com remifentanila na dose de 0,3æg/kg/min, através de bomba de seringa. Em GII, os animais receberam o mesmo tratamento de GI, só que ao invés de receberem o propofol por infusão alvo controlada, receberam o propofol a 5mg/kg como dose de indução e como manutenção, receberam o propofol em infusão contínua de velocidade fixa, na dose de 0,2mg/kg/min. Assim, compararam-se as duas técnicas de infusão, a de velocidade fixa e a alvo controlada, concluindo-se que as doses de propofol utilizadas em ambas as técnicas, após o pré-tratamento de levomepromazina e associadas ao opióide, foram eficazes para a realização cirúrgica, promovendo bradicardia e discreta hipotensão, porém estabilidade hemogasométrica e respiratória... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Total venous anesthesia has many advantages as it does not pollute environmental air, can be easily used in remote sites, provides cardiovascular stability and good recovery quality. Due to its pharmacology, propofol is one of the most frequently used drugs in continuous infusions. Recently, advances have also been observed in total venous anesthesia with the use of target-controlled infusions based on real-time pharmacodynamic and pharmacokinetic drug simulations in Veterinary Medicine. As a result, this study aimed at applying this type of anesthesia by using it in female dogs for the performance of ovariosalpingohysterectomy surgery. To that end, twenty female dogs were anesthetized after free consent was given by their owners. The animals were divided into two groups (GI and GII). In GI, the dogs were pre-treated with methotrimeprazine at a dose of 0.5mg/kg IV and anesthetized with propofol by target-controlled infusion at an induction dose of 3.5æg/ml and a maintenance dose of 1.5 æg/ml IV by means of a Harvard infusion pump associated with remifentanil at a dose of 0.3æg/kg/min by means of a syringe pump. In GII, the animals received the same treatment as that given to GI, except that instead of receiving propofol by target-controlled infusion, they were given propofol at 5mg/kg as an induction dose. As maintenance, they received propofol by single-speed continuous infusion at a dose of 0.2mg/kg/min. Hence, two infusion techniques, fixed-speed infusion and target-controlled infusion, were compared, leading to the conclusion that the doses of propofol used in both techniques, after pre-treated with methotrimeprazine, associated with the opioid were efficient for surgery performance as they promoted bradycardia and discreet hypotension, but hemogasometric and respiratory stability, futher good muscle relaxation, more evident in fixed-speed infusion... (Complete abstract click electronic access below) / Doutor

Catalisadores Ziegler-Natta (Z-N) de 4ª geração são preparados com suporte de dicloreto de magnésio com morfologia controlada, obtidos a partir de adutos etanólicos de dicloreto de magnésio (MgCl2.nEtOH). O objetivo deste trabalho foi otimizar o balanço entre as variáveis independentes concentração de reagentes, velocidade de agitação da emulsão e pressão de transferência, na preparação do aduto com controle morfológico. Os adutos etanólicos com controle da morfologia esférica foram preparados pela transferência controlada do aduto fundido a 125 ºC e precipitação por resfriamento brusco (quenching) em não-solvente a – 50 ºC, utilizando o método Controlled Turbulence Emulsion Method (CTEM). A ativação do MgCl2.nEtOH foi feita pela rota química para remoção do etanol e consequente aumento da área superficial do suporte. Os adutos foram preparados com razão molar EtOH/MgCl2 de 3,5 ou 63% (p/p) de etanol. Os experimentos foram realizados segundo planejamento fatorial 23 a dois níveis e ponto central replicado. As variáveis dependentes foram o diâmetro médio e distribuição de tamanho das partículas do suporte, densidade aparente compactada, morfologia e teor de álcool incorporado no aduto. Os catalisadores Z-N’s foram obtidos a partir dos suportes tratados com TiCl4 e um doador de elétrons interno, e testados em polimerização padrão de propileno. Foi observado que o controle do tamanho (diâmetro médio) da partícula do suporte é altamente dependente da velocidade de transferência, controlada pela pressão no reator de fusão. A concentração do reagente ([MgCl2]) teve efeito significativo nas quatro variáveis dependentes. A velocidade de agitação no reator de fusão ou da emulsão do aduto fundido teve efeito significativo somente na morfologia do suporte, sendo este efeito menor que o observado para a pressão de transferência. A velocidade de agitação não teve significância no processo de transferência CTEM, sendo este mais suscetível a variação da pressão no reator. / 4th Generation Ziegler-Natta catalysts (Z-N catalysts) are prepared with magnesium dichloride support with controlled morphology, obtained from ethanolic adducts of magnesium dichloride (MgCl2.nEtOH). The objective of this work was to optimize the balance between the independent variables reagent concentration, emulsion agitation speed and transfer pressure, in the preparation of the adduct with morphological control. The ethanolic adducts with spherical morphology control were prepared by controlled transfer of the molten adduct at 125 °C and quenching in nonsolvent at - 50 °C using the Controlled Turbulence Emulsion Method (CTEM). The activation of MgCl2.nEtOH was done by chemical route to remove the ethanol and consequently increase the surface area of the support. The adducts were prepared with EtOH/MgCl2 molar ratio of 3.5 or 63% (w/w) ethanol. The experiments were performed according to factorial design 23 at two levels and replicated central point. The dependent variables were the mean diameter and particle size distribution of the carrier, compacted bulk density, morphology and alcohol content incorporated in the adduct. The Z-N’s catalysts were obtained from TiCl4-treated media and an internal electron donor, and tested in standard polypropylene polymerization. It has been observed that size control (median diameter) of the carrier particle is highly dependent on the transfer rate, controlled by the pressure in the fusion reactor. The concentration of the reagent ( [MgCl2] ) had a significant effect on the four dependent variables. The stirring rate in the melt reactor or the cast adduct emulsion had significant effect only on the morphology of the support, this effect being smaller than that observed for the transfer pressure. The stirring speed was not significant in the CTEM transfer process, which is more susceptible to pressure variation in the reactor.