No description available.

The objective of this study was to determine how neurons within the right atrial ganglionated plexus (RAGP) and posterior atrial ganglionated plexus (PAGP) interact to modulate right atrial chronotropic, dromotropic, and inotropic function, particularly with respect to their extracardiac vagal and sympathetic efferent neuronal inputs. Surgical ablation of the PAGP (PAGPx) attenuated vagally mediated bradycardia by 26%; it reduced heart rate slowing evoked by vagal stimulation superimposed on sympathetically mediated tachycardia by 36%. RAGP ablation (RAGPx) eliminated vagally mediated bradycardia, while retaining the vagally induced suppression of sympathetic-mediated tachycardia (-83%). After combined RAGPx and PAGPx, vagal stimulation still reduced sympathetic-mediated tachycardia (-47%). After RAGPx alone and after PAGPx alone, stimulation of the vagi still produced negative dromotropic effects, although these changes were attenuated compared with the intact state. Negative dromotropic responses to vagal stimulation were further attenuated after combined ablation, but parasympathetic inhibition of atrioventricular nodal conduction was still demonstrable in most animals. Finally, neither RAGPx nor PAGPx altered autonomic regulation of right atrial inotropic function. These data indicate that multiple aggregates of neurons within the intrinsic cardiac nervous system are involved in sinoatrial nodal regulation. Whereas parasympathetic efferent neurons regulating the right atrium, including the sinoatrial node, are primarily located within the RAGP, prejunctional parasympathetic-sympathetic interactions regulating right atrial function also involve neurons within the PAGP.

Controlled release formulations deliver an active ingredient over an extended period of time. It is an ideal dosage form for an active ingredient with a short elimination half-life. An active ingredient with a short elimination half-life would be released in small portions over an extended period of time and thus less frequent administration is necessary and this improve patient compliance. Other advantages of these formulations include: decreased side effects, constant drug levels in the blood, improvement in treatment efficiency and reduction in cost of administration. Controlled release beads are formulated in such a way that the active ingredient is embedded in a matrix of insoluble substance like chitosan; the dissolving drug then has to find its way through the pores of the matrix into the surrounding medium. The chitosan matrix swells to form a gel, the drug then has to first dissolve in the matrix and diffuse through the outer surface into the surrounding medium. Chitosan is a biocompatible, biodegradable polymer of natural origin. It has mucoadhesive properties as well as the ability to manipulate the tight junctions in the epithelium membrane and these properties have qualified chitosan as an effective drug carrier in controlled release dosage forms. The effect of a modern controlled release polymer namely Kollidon® SR in combination with chitosan on drug release was investigated. Ketoprofen was chosen as model drug. Ketoprofen is an anti-inflammatory drug that causes gastrointestinal side effects in conventional dosage forms. Ketoprofen has a short elimination half-life of 2.05 ± 0.58 h and this characteristic makes it an ideal candidate for use in a controlled release formulation. The aim of this study was to achieve controlled release and minimize gastrointestinal effects of ketoprofen with chitosan particles. Kollidon® SR was used as polymer because it exhibits pH independent release characteristics and previous studies have shown potential for this combination. Chitosan beads and chitosan-Kollidon® SR beads, as well as chitosan granules and chitosan-Kollidon® SR granules, were prepared and investigated as potential controlled release formulations. Chitosan beads were prepared through the inotropic gelation method using tripolyphosphate as a cross linking agent. Granules were prepared through wet granulation using 2% v/v acetic acid as the granulating fluid or by dissolving ketoprofen in ethanol and Kollidon® SR in 2-pyrrolidinone and using the solution as granulating fluid. Kollidon® SR was added in concentrations of 0.25, 0.5 and 1% (w/v) in the bead formulations and concentrations of 1, 5 and 10% (w/w) in the granule formulations. The beads and granules were characterised by evaluating the following properties: morphology, drug loading and drug release. Additionally swelling and friability tests were also conducted on the bead formulations. The cross linking times of the bead formulations were varied to investigate the effect of cross linking time on the characteristics of the beads. Chitosan-Kollidon® SR beads showed promising results for controlled release formulations and ketoprofen were released over an extended period of time. Drug loading of the plain chitosan beads was 74.65 ± 0.71% and it was noted that the inclusion of Kollidon® SR in the beads resulted in an increase in drug loading and the formulation containing 1% (w/v) Kollidon® SR, cross linked for 30 minutes had a drug loading of 77.38 ± 0.01%. Drug loading of the beads that were cross linked for a longer time were slightly lower which is an indication that some of the drug might have leached out during cross linking. The degree of swelling was promising with some beads swelling to a degree of 2.5 in phosphate buffer solution pH 5.6. Granules had a drug loading between 81.73 ± 1.53% and 93.30 ± 0.50%. Ketoprofen release from the beads and the granules in PBS pH 7.40 at 37 °C over a period of 6 hours were investigated. The bead formulations were more effective in achieving controlled release and it was noted that the bead formulations that was cross linked for a longer period was more efficient in achieving controlled release. The granules did not form a matrix and were not effective in achieving controlled release. Controlled release of ketoprofen were achieved and the results show potential for chitosan-Kollidon® SR formulations in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Inotropic support for the failing myocardium as the therapy for xi congestive heart failure (CHF) is intended to achieve an increase in cardiac output via positive responses in myocardial contractility and vasodilation. A novel approach to differentiate these two responses is the use of an animal with an implanted total artificial heart (TAH). Three inotropic drugs, dobutamine, enoximone, and pimobendan, were tested in eight animals with their natural heart intact and five animals implanted with a TAH. Baseline values of the TAH and natural heart (NH) were compared to determine their hemodynamic similarities. Each of the three drugs was given randomly to the animals in dosages similar to human clinical doses. Peak responses were recorded and analyzed. All three drugs caused an increase in contractility and cardiac output in the NH animals. Dobutamine and pimobendan also caused a significant increase in heart rate at higher dosages whereas enoximone did not. Dobutamine caused an increase in left ventricle work, as did pimobendan at the first dose given; at higher doses of pimobendan, the left ventricular work returned to baseline. However, at the doses tested, the left ventricular stroke work during enoximone administration decreased. Vasodilation (the only drug stimulation response in the TAH model) was also observed with the administration of the drugs in T AH animals, and all three caused decreases in systemic and pulmonary vascular resistance. Dobutamine and pimobendan caused an increase in left and right atrial pressures (because of the mechanical heart not being adjusted to compensate the increased return). There was also a reduction in systemic and pulmonary resistance. Enoximone caused severe pulmonary hypertension in the TAH animals, possibly due to stimulus of platelets to release vasoconstrictive substances. Thus, dobutamine, enoximone, and pimobendan significantly contribute to increases in output by vasodilation in animals with a natural heart. Similarly, dobutamine and pimobendan's vasodilatory action is identified in an animal with a TAH. However, enoximone's hypertensive action on the pulmonary vasculature of a TAH animal may offer an insight to the toxicity of enoximone when used after recent surgery.

Controlled release formulations deliver an active ingredient over an extended period of time. It is an ideal dosage form for an active ingredient with a short elimination half-life. An active ingredient with a short elimination half-life would be released in small portions over an extended period of time and thus less frequent administration is necessary and this improve patient compliance. Other advantages of these formulations include: decreased side effects, constant drug levels in the blood, improvement in treatment efficiency and reduction in cost of administration. Controlled release beads are formulated in such a way that the active ingredient is embedded in a matrix of insoluble substance like chitosan; the dissolving drug then has to find its way through the pores of the matrix into the surrounding medium. The chitosan matrix swells to form a gel, the drug then has to first dissolve in the matrix and diffuse through the outer surface into the surrounding medium. Chitosan is a biocompatible, biodegradable polymer of natural origin. It has mucoadhesive properties as well as the ability to manipulate the tight junctions in the epithelium membrane and these properties have qualified chitosan as an effective drug carrier in controlled release dosage forms. The effect of a modern controlled release polymer namely Kollidon® SR in combination with chitosan on drug release was investigated. Ketoprofen was chosen as model drug. Ketoprofen is an anti-inflammatory drug that causes gastrointestinal side effects in conventional dosage forms. Ketoprofen has a short elimination half-life of 2.05 ± 0.58 h and this characteristic makes it an ideal candidate for use in a controlled release formulation. The aim of this study was to achieve controlled release and minimize gastrointestinal effects of ketoprofen with chitosan particles. Kollidon® SR was used as polymer because it exhibits pH independent release characteristics and previous studies have shown potential for this combination. Chitosan beads and chitosan-Kollidon® SR beads, as well as chitosan granules and chitosan-Kollidon® SR granules, were prepared and investigated as potential controlled release formulations. Chitosan beads were prepared through the inotropic gelation method using tripolyphosphate as a cross linking agent. Granules were prepared through wet granulation using 2% v/v acetic acid as the granulating fluid or by dissolving ketoprofen in ethanol and Kollidon® SR in 2-pyrrolidinone and using the solution as granulating fluid. Kollidon® SR was added in concentrations of 0.25, 0.5 and 1% (w/v) in the bead formulations and concentrations of 1, 5 and 10% (w/w) in the granule formulations. The beads and granules were characterised by evaluating the following properties: morphology, drug loading and drug release. Additionally swelling and friability tests were also conducted on the bead formulations. The cross linking times of the bead formulations were varied to investigate the effect of cross linking time on the characteristics of the beads. Chitosan-Kollidon® SR beads showed promising results for controlled release formulations and ketoprofen were released over an extended period of time. Drug loading of the plain chitosan beads was 74.65 ± 0.71% and it was noted that the inclusion of Kollidon® SR in the beads resulted in an increase in drug loading and the formulation containing 1% (w/v) Kollidon® SR, cross linked for 30 minutes had a drug loading of 77.38 ± 0.01%. Drug loading of the beads that were cross linked for a longer time were slightly lower which is an indication that some of the drug might have leached out during cross linking. The degree of swelling was promising with some beads swelling to a degree of 2.5 in phosphate buffer solution pH 5.6. Granules had a drug loading between 81.73 ± 1.53% and 93.30 ± 0.50%. Ketoprofen release from the beads and the granules in PBS pH 7.40 at 37 °C over a period of 6 hours were investigated. The bead formulations were more effective in achieving controlled release and it was noted that the bead formulations that was cross linked for a longer period was more efficient in achieving controlled release. The granules did not form a matrix and were not effective in achieving controlled release. Controlled release of ketoprofen were achieved and the results show potential for chitosan-Kollidon® SR formulations in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Orientadores: José Wilson Magalhães Bassani, Pedro Xavier de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-21T21:15:04Z (GMT). No. of bitstreams: 1 FimNeto_Arnaldo_M.pdf: 1424780 bytes, checksum: 73cab0ac057a4075313d76ce8e26bbbf (MD5) Previous issue date: 2012 / Resumo: O vaso dorsal de insetos tem sido proposto como um modelo mais simples para estudar o desempenho do coração em diferentes condições. O vaso dorsal apresenta características semelhantes às encontradas no coração de vertebrados (e.g. atividades cronotrópica e inotrópica dependentes do ambiente iônico e da ação de neurotransmissores), mas os mecanismos envolvidos na sua atividade inotrópica estão pouco explorados. Neste trabalho, desenvolvemos instrumentação e métodos com o objetivo de estudar aspectos da atividade inotrópica in situ do vaso dorsal do coleóptero T. molitor. Foram desenvolvidos dois métodos para estimar a redução do diâmetro luminal do vaso dorsal durante as contrações. Um foi baseado na detecção da "quantidade de luz" emitida por um conjunto de pixels de uma imagem de vídeo do centro do lúmen do vaso, e o outro, na medição do diâmetro do lúmen, como visto na imagem de vídeo. Os métodos se mostraram aplicáveis, mas o último foi menos sensível a variações das condições experimentais. O diâmetro diastólico luminal foi 148,70 ± 5,09 ?m, consistente com dados da literatura. Com a instrumentação desenvolvida, e a partir do controle da frequência de contrações por meio de estimulação elétrica, foi possível estudar o efeito de intervenções inotrópicas. A relação entre a redução de diâmetro (amplitude da contração) e frequência foi negativa (p< 0,05 na faixa de 1,0-2,5 Hz). A incubação do coração com cafeína, que tipicamente depleta a carga de Ca2+ do reticulo sarcoplasmático (RS), produziu um efeito inotrópico negativo, diminuindo a redução sistólica do diâmetro luminal de 56,32 ± 4,85 para 35,05 ± 3,86 % (n = 7, p< 0,05), o que sugere um papel funcional do RS na atividade inotrópica. O aumento da concentração externa de Ca2+ ([Ca2+]o) na faixa de 0,5 a 8,0 mM, durante estimulação elétrica a 1,5 Hz, aumentou significativamente a amplitude das contrações de 43,23 ± 2,51 para 66,60 ± 3,31% do diâmetro luminal (n=7, p< 0,05). Os resultados mostram que ambos [Ca2+]o e carga de Ca2+ do RS são fatores regulatórios importantes da atividade contrátil do vaso dorsal do T. molitor, além de afetar a atividade cronotrópica, como demonstrada previamente no nosso laboratório / Abstract: The dorsal vessel of insects has been proposed as a simplified model to study the performance of the heart. The dorsal vessel shares important features with the vertebrate heart (e.g. chronotropic and inotropic activities affected by the ionic environment and neurotransmitters), but the mechanisms involved in its inotropic activity are not clear yet. In this work, we developed instrumentation and methods aiming at studying the contractile activity of the in situ dorsal vessel of the coleopterum T. molitor. Two methods were developed to estimate the decrease in the dorsal vessel lumen during contractions. One was based on the detection of the "amount of light" emitted by a set of pixels at the center of the dorsal vessel video image, and the other, on the measurement of the luminal width in the dorsal vessel image. The methods were shown to be applicable, but the latter was less sensitive to variations in the experimental conditions. The measured diastolic diameter of the dorsal vessel was 148.70 ± 5.09 ?m, which was consistent with the values in the literature. With the developed instrumentation, and by controlling the beating rate by electrical stimulation, it was possible to study the effect of inotropic interventions. The relationship between contraction amplitude and stimulation rate was negative (p< 0.05 in the range of 1.0-2.5 Hz). Incubation of the heart with caffeine, which typically depletes the sarcoplasmic reticulum (SR) Ca2+ load, produced a negative inotropic effect, decreasing the systolic reduction of luminal diameter from 56.32 ± 4.85 to 35.05 ± 3.86 % (n = 7, p< 0.05), which is suggestive of a functional participation of the SR in the inotropic activity. Increasing the extracellular Ca2+ concentration ([Ca2+]o) in the range of 0.5 - 8.0 mM during electrical stimulation at 1.5 Hz significantly increased contraction amplitude from 43.23 ± 2.51 to 66.60 ± 3.31% of the luminal diameter; (n=7, p< 0.05). The present results show that both [Ca2+]o and the SR Ca2+ load are important factors in the regulation of the contractile activity of the T. molitor dorsal vessel, in addition to their influence on the chronotropic activity, as previously observed in this laboratory / Mestrado / Engenharia Biomedica / Mestre em Engenharia Elétrica

A hipotensão trans-anestésica é frequente em equinos submetidos a anestesia geral inalatória e pode desencadear graves complicações pós-anestésicas. Consequentemente, o tratamento adequado deve ser instituído rapidamente, entretanto, há poucos estudos na espécie que auxiliem na escolha do fármaco simpatomimético quando o agente inalatório empregado é o isofluorano. Dessa forma, o presente estudo teve como objetivo comparar os efeitos cardiovasculares da efedrina, com os da dobutamina. O experimento foi dividido em duas fases: na Fase I foram utilizados 13 cavalos monitorados com cateter em artéria pulmonar o que possibilitou avaliação hemodinâmica, além da obtenção de sangue venoso misto. Ademais, foi realizada a mensuração do lactato sérico e troponina I e de parâmetros de ventilação e oxigenação, sendo que os animais não foram submetidos a procedimento cirúrgico. Na Fase II foram utilizados 22 equinos da rotina do serviço de cirurgia de grandes animais, submetidos a avaliação cardiovascular (frequência cardíaca e pressão arterial sistêmica), parâmetros de ventilação e oxigenação, avaliação de eletrólitos e lactato sérico. Em ambas as fases os animais foram randomizados entre o grupo dobutamina e grupo efedrina, e o tratamento teve início após detecção de hipotensão arterial (PAM <60 mmHg). O grupo dobutamina recebeu taxa de infusão inicial de 1 &micro;g/kg/min, aumentada conforme necessário até atingir a PAM igual a 70mmHg ou taxa máxima de 5 &micro;g/kg/min. Já o grupo efedrina foi tratado com infusão contínua na dose de 20 &micro;g/kg/min até atingir PAM de 60mmHg, depois reduzida para 10 &micro;g/kg/min até obter PAM igual 70mmHg e posteriormente mantida em 5 &micro;g/kg/min. Após determinação da normalidade, os dados foram submetidos à ANOVA com duas variáveis independentes e pós teste de Bonferroni. Na Fase I os dois grupos resgataram a pressão arterial em tempos semelhantes, diferindo entre si quanto a frequência cardíaca, que foi superior no grupo efedrina (p=0,0098), porém com a ocorrência de arritimias apenas no grupo dobutamina; e quanto a pressão de oclusão da artéria pulmonar, a qual se elevou apenas no grupo dobutamina (p&lt;0,0001). Os dois protocolos experimentais elevaram de forma significativa as pressões arteriais, o débito cardíaco (p=0,0012), índice cardíaco (p=0,0013), resistência vascular sistêmica (p=0,008), índice de resistência vascular sistêmica (p=0,0001), enquanto o índice sistólico elevou-se significativamente apenas no grupo dobutamina (p=0,003). Dentre os índices de oxigenação e gases sanguíneos TEO2 (p=0,0008), IDO2 (p&lt;0,0001), SvO2 (p= 0,0005) e SpO2 (p=0,006) diferiram entre tempos nos dois grupos, sem diferir entre grupos. Apenas no grupo efedrina verificou-se redução da C(a-v)O2 (p=0,02), porém sem diferir entre grupos. O lactato, utilizado como indicador de perfusão tecidual não diferiu entre tempos, nem entre grupos, assim como a Troponina I, biomarcador de lesão miocárdica. O K reduziu significativamente em ambos os grupos nessa fase, enquanto o cálcio reduziu apenas no grupo efedrina. Na fase II verificou-se que a pressão arterial se elevou em tempos semelhantes em ambos os grupos, porém não foram observadas alterações na FC. Parâmetros de ventilação e oxigenação também não sofreram alterações, tampouco diferiram entre os grupos, com exceção da PaCO2 que se elevou significativamente (p=0,006) e a concentração sérica de Ca que diminuiu (p=0,01) apenas no grupo efedrina. Conclui-se que ambos os fármacos são efetivos para o tratamento de hipotensão em equinos anestesiados com isofluorano. / Trans-anesthetic hypotension is frequent in horses submitted to general inhalation anesthesia and may lead to severe post-anesthetic complications. Consequently, adequate treatment should be instituted rapidly, however, there are few studies in the species that assist in the choice of sympathomimetic drug when the inhalant agent employed is isoflurane. Thus, the present study aimed to compare the cardiovascular effects of ephedrine with those of dobutamine. The experiment was divided into two phases: in Phase I, 13 horses were monitored with a pulmonary artery catheter, which allowed a hemodynamic evaluation, in addition to obtaining venous mixed blood. In addition, measurement of serum lactate, troponin I and ventilation and oxygenation parameters were performed, the animals were not submitted to a surgical procedure. In Phase II, 22 horses from large animals surgery routine were submitted to cardiovascular evaluation (heart rate and systemic arterial pressure), ventilation and oxygenation parameters, electrolyte evaluation and serum lactate. In both phases the animals were randomized in two groups, the treatment started after detection of hypotension (MAP &lt;60 mmHg). The dobutamine group received an initial infusion rate of 1 &micro;g/kg/min, increased as needed until the MAP was equal to 70 mmHg or a maximum rate of 5 &micro;g/kg/min. On the other hand, the ephedrine group was treated with continuous infusion at a dose of 20 g/kg/min until it achieved a PAM of 60 mmHg, then reduced to 10 &micro;g/kg/min until the PAM was 70 mmHg and subsequently maintained at 5 &micro;g/kg/min. After determination of normality, the data were submitted to ANOVA with two independent variables and post Bonferroni test. In Phase I, the two groups recovered blood pressure at similar times, differing in heart rate, which was higher in the ephedrine group (p = 0.0098), but with the occurrence of arrhythmias only in the dobutamine group; and the pulmonary artery occlusion pressure, which only increased in the dobutamine group (p &lt;0.0001). The two experimental protocols significantly elevated arterial pressures, cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p = 0.0001), whereas the systolic index increased significantly only in the dobutamine group (p = 0.003). Among the rates of oxygenation and blood gases TEO2 (p = 0.0008), IDO2 (p &lt;0.0001), SvO2 (p = 0.0005) and SpO2 (p = 0.006) differed between times in the two groups, without differing between groups. Only in the ephedrine group C(a-v)O2 decrease signficantly (p = 0.02), but did not differ between groups. Lactate, used as an indicator of tissue perfusion did not differ between times, niether between groups, as did Troponin I, a biomarker of myocardial injury. Potassium significantly reduced in both groups in this phase, while calcium reduced only in the ephedrine group. In phase II, it was found that blood pressure increased at similar times in both groups, but no changes were observed in HR. Ventilation and oxygenation parameters also did not change, neither differ between groups, with the exception of PaCO2 that increased significantly (p = 0.006) and the Ca concentration that decreased (p = 0.01) only in the ephedrine group. It is concluded that both drugs are effective for the treatment of hypotension in horses anesthetized with isoflurane.

Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Chitosan has proven through the years as a versatile biomaterial to be used in pharmaceutical applications. Its mucoadhesive properties as well as its ability to manipulate the tight junctions in epithelium membranes have qualified it as an effective drug carrier in controlled drug delivery systems. Microparticles or beads as they are forward called in this study have advantages over conventional drug dosage forms because of a large surface to volume ratio and have the ability to target a specific site for drug release. Indomethacin is an anti-inflammatory drug that causes gastrointestinal side effects in conventional immediate-release dosage forms. The goal is to manipulate the drug delivery vehicle to target the intestines/colon as the site for drug delivery and to minimize this side effect. Thus chitosan beads have been chosen as a drug delivery system for indomethacin in this study. Chitosan beads have been prepared through the ionotropic gelation method using tripolyphophate (TPP) as a cross-linking agent. To prepare the most effective bead to encapsulate indomethacin different formulation and system variables (pH of the TPP solution, the concentration of the TPP solution as well as the indomethacin concentration) have been evaluated according to the following parameters: morphology, drug loading capacity and swelling capability. The ideal pH of the TPP solution was determined at 8.7 and the most effective TPP and indomethacin concentration were 5% w/v and 4% w/v respectively. The chitosan concentration was kept at 3% w/v throughout the study. These concentrations were used to examine the effect of pharmaceutical excipients on the indomethacin release from chitosan beads. The effect of the different excipients namely, ExplotabⒽ(0.25% w/v), Ac-Di-SolⓀ (0.5% w/v) and Vitamin C (0.25% w/v), on the morphology, drug loading capacity, swelling capability as well as the drug release of indomethacin chitosan beads (ICB's) were also studied. The excipients were used in the individually above mentioned concentrations and in combination with each other in the same concentrations. These formulations were used in dissolution studies over a period of 6 hours in PBS pH 7.4 solutions. The indomethacin release rate increased when an excipient was added to the formulation and it dramatically increased when the excipients were added in their various combinations, compared to the formulation that did not contain excipients. / Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release formulations offer many advantages over conventional dosage forms. These include reduced plasma fluctuations and improved patient comp1i:nce. Complex controlled release formulations such as those with enteric release properties, often require additional steps in the production phase. The costs and economic impact associated with these complex controlled release dosage formulations often outweigh the immediate benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations, the drug is generally dispersed throughout a polymer matrix. The rate of drug release is often determined by the viscosity or complexity of the polymer matrix through which the drug needs to diffuse in order to be released. With enteric release the polymer coating, insoluble in an acidic environment is often applied in the final phase of production. Chitosan is a versatile polymer of natural origin with many favourable characteristics. These include its safety, biocompatibility, and biodegradability. Simple methods can be applied and modified to produce controlled release particles form chitosan. The effect of modern controlled release polymers such as Aqoat AS-HF, Eudragit SlOO and Kollidon SR was investigated. Chitosan beads and chitosan-polymer beads, as well as chitosan granules and chitosan-polymer granules, were prepared and investigated as possible controlled release formulations. Ketoprofen was chosen as the model drug. Chitosan beads and chitosan-polymer beads were prepared by inotropic gelation in tripolyphosphate. Chitosan granules and chitosan-polymer matrix granules were prepared by binding chitosan with an acetic acid solution as a granulating system. The beads and granules appeared differed in appearance as well as in the results obtained from various experiments. Granules prepared in the study did not appear to be effective with regards to enteric and controlled release. Beads prepared form Kollidon SR appeared to be effective with regards to enteric and controlled release, with Kollidon 1% and 5% w/v chitosan beads achieving good drug loading of up to 73.13% and releasing less than 15 % of the total drug content in 0.1 M HCI after 60 minutes. Drug release continued steadily for up to 360 minutes in pH 7.2. It was concluded that Kollidon SR loaded chitosan beads nay be a viable controlled release dosage form with enteric release properties, and that future experiments, possibly with lower polymer concentrations, are worthwhile / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.