Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells.

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/- 0.370 mg/kg, and the cells' metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new "easy-to-make" nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

Modification of chicha gum: Antibacterial activity, ex vivo mucoadhesion, antioxidant activity and cellular viability.

The aim of the present work was to modify the exuded gum of Sterculia striata tree by an amination reaction. The viscosity and zero potential of the chicha gum varied as a function of pH. The modification was confirmed by X-ray diffraction (XRD), infrared spectroscopy (FTIR), size exclusion chromatography (SEC), zeta potential, thermogravimetric analysis (TG), and differential scanning calorimetry (DSC). Furthermore, the chemical modification changed the molar mass and surface charge of the chicha gum. In addition, the gums were used in tests for ex vivo mucoadhesion strength, antibacterial activity against the standard strain of Staphylococcus aureus (ATCC 25923), inhibitory activity of α-glucosidase, antioxidant capacity, and viability of Caco-2 cells. Through these tests, it was found that amination caused an increase in the mucoadhesive and inhibitory activity of chicha gum against the bacterium Staphylococcus aureus. In addition, the gums (pure and modified) showed antioxidant capacity and an inhibitory effect against the α-glucosidase enzyme and did not show cytotoxic potential.

Trichilia catigua and Turnera diffusa extracts: In vitro inhibition of tyrosinase, antiglycation activity and effects on enzymes and pathways engaged in the neuroinflammatory process.

ETHNOPHARMACOLOGICAL RELEVANCE: Flavonoids interact with multiple targets in Central Nervous System resulting in a broad neuroprotection mediated by complementary processes and synergic interactions. Therefore, flavonoid-based therapies may input positive outcomes in the prevention and early management of neurodegenerative diseases. In Brazilian folk medicine Trichilia catigua is used for its neuroactive properties, such as neurostimulant, antioxidant and anti-neuroinflammatory, while Turnera diffusa is traditionally used as a tonic in neurasthenia. Both species are known to be rich in flavonoids. AIM OF THE STUDY: To study aqueous extracts of T. catigua and T. diffusa in terms of their antioxidant and antiglycation effects, inhibition of tyrosinase activity, and interaction with enzymes and pathways engaged in neuroinflammation. Moreover, whenever possible, to establish a relationship between the studied activities and the traditional usage of the species. MATERIALS AND METHODS: The phenolic profiles of the aqueous extracts were validated by HPLC-DAD. The effect of the extracts over mushroom tyrosinase and 5-lipoxygenase activities, as well as their capacity to impair bovine serum albumin glycation, were assessed by in vitro assays. The anti-neuroinflammatory potential of the same extracts was evaluated by their capacity to mitigate the pro-inflammatory stimulus induced in BV-2 microglia cells by interferon-gamma. RESULTS: T. catigua extract, a rich mixture of phenolic acids, catechins and flavonolignans, excels by its ability to decrease lipid peroxidation (EC50 = 227.18 ±â€¯9.04 µg/mL), and to work as anti-glycation agent, and inhibitor of both tyrosinase and 5-lipoxigenase (IC50 = 358.84 ±â€¯19.05 and 56.25 ±â€¯14.53 µg/mL, respectively). However, only T. diffusa extract, mainly composed by luteolin derivatives, is able to lower NO production by BV-2 microglia cells stimulated with interferon-gamma, despite its lower activities in the other assays. CONCLUSIONS: Overall, this work highlights the value of medicinal plant extracts as sources of bioactive flavonoid-rich extracts with neuroactive effects. Furthermore, these results support their application as alternative strategies to develop functional foods and therapeutics to fight chronic neurodegenerative disorders.

Sterculia striata gum as a potential oral delivery system for protein drugs.

Natural polysaccharides have been investigated as vehicles for oral insulin administration. Because of their non-toxic, renewable, low cost and readily available properties, gums find multiple applications in the pharmaceutical industry. This work aimed to develop a Sterculia striata gum-based formulation associated with additional biopolymers (dextran sulfate, chitosan, and albumin), a crosslinking agent (calcium chloride) and stabilizing agents (polyethylene glycol and poloxamer 188), to increase the oral bioavailability of proteins. Insulin was used as a model drug and the methods used to prepare the formulation were based on ionotropic pregelation followed by electrolytic complexation of oppositely charged biopolymers under controlled pH conditions. The developed formulation was characterized to validate its efficacy, by the determination of its average particle size (622 nm), the insulin encapsulation efficiency (70%), stability in storage for 30 days, and the in vitro mucoadhesion strength (92.46 mN). Additionally, the developed formulation preserved about 64% of initial insulin dose in a simulated gastric medium. This study proposed, for the first time, a Sterculia striata gum-based insulin delivery system with potential for the oral administration of protein drugs, being considered a valid alternative for efficient delivery of those drugs.

Solvent-free synthesis of acetylated cashew gum for oral delivery system of insulin.

Cashew gum (CG) is a biopolymer that presents a favorable chemical environment for structural modifications, which leads to more stable and resistant colloidal systems. The gum was subjected to an acetylation reaction using a fast, simple, solvent-free and low cost methodology. The derivative was characterized by infrared and NMR spectroscopy, elemental analysis, coefficient of solubility and zeta potential. The modified biopolymer was used as a platform for drug delivery systems using insulin as a model drug. Nanoparticles were developed through the technique of polyelectrolytic complexation and were characterized by size, surface charge, entrapment efficiency and gastrointestinal release profile. The nanoparticles presented size of 460 nm with a 52.5% efficiency of entrapment of insulin and the electrostatic stabilization was suggested by the zeta potential of + 30.6 mV. Sustained release of insulin was observed for up to 24 h. The results showed that acetylated cashew gum (ACG) presented potential as a vehicle for sustained oral insulin release.

Methyl-ß-cyclodextrin Inclusion Complex with ß-Caryophyllene: Preparation, Characterization, and Improvement of Pharmacological Activities.

ß-Caryophyllene (BCP) is a sesquiterpene that shows high potential in pharmacological applications. However, these have been drastically limited by the respective volatility and poor water solubility. The present study investigates the formation of inclusion complexes between BCP and methyl-ß-cyclodextrin (MßCD) and shows that these complexes promote a significant improvement of the anti-inflammatory, gastric protection, and antioxidant activities relative to neat BCP. It is shown that the solubility of BCP is significantly increased through complexation in phase solubility studies. Inclusion complexes with MßCD in solid state were prepared by three different methods, kneading, rotary evaporation, and lyophilization, with the latter confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, scanning electron microscopy, 1H NMR spectroscopy, and molecular dynamics studies. This study provides for the first time a full characterization of inclusion complexes between BCP and MßCD and highlights the impact of complex formation upon pharmacological activity.

Crystalline forms of nonprotein drugs filed in Brazil from 1995-2005.

In the present study, we evaluated 457 patent applications filed for crystalline forms of nonprotein drugs during the period 1995-2005 in Brazil. Online searches were conducted using the Instituto Nacional da Propriedade Industrial patent database and the Derwent Innovations Index(®). It was found that no patent applications in this area were filed by Brazilian applicants. It was also noted that only 61% of patent applications included the characterization of three or more crystalline phase techniques. In most applications, no determination of purity was provided for chemical and/or crystalline phases. In a subset of patent applications, those for blockbuster drugs, we found that approximately 90% did not meet Instituto Nacional da Propriedade Industrial acceptance criteria nor the criteria developed in this study. These results reveal that appropriate and thorough characterization of the crystalline forms of drugs is, indeed, lacking in patent applications.

Development of a doxazosin and finasteride transdermal system for combination therapy of benign prostatic hyperplasia.

The treatment of benign prostatic hyperplasia can be accomplished by the use of different drugs including, doxazosin, an α-1 adrenergic antagonist, and finasteride (FIN), a 5-α reductase inhibitor. Traditionally, treatments using these drugs have been administered as either a mono or combination therapy by the oral route. A transdermal delivery system optimized for doxazosin and FIN combination therapy would provide increased patient adherence and facilitate dose adjustment. Doxazosin base (DB) was prepared from doxazosin mesylate and characterized together with FIN, by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The permeation enhancers, azone and lauric acid, and the gelling agents, hydroxypropyl cellulose (HPC) and Poloxamer 407 (P407), were evaluated to determine their ability to promote in vitro permeation of drugs through the pig ear epidermis. Successful preparation of DB was confirmed by evaluating the XRD, DSC, and NMR patterns and in vitro studies revealed that 3% (w/w) azone was the best permeation enhancer. When P407 gel was compared with HPC gel, it showed reduced lag time and promoted higher permeation of both drugs. This may be because of the interactions of the former with the stratum corneum, which disorganizes the lipid structure and consequently promotes higher drug permeation.

The systems containing clays and clay minerals from modified drug release: a review.

Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied.

Solid dispersions of imidazolidinedione by PEG and PVP polymers with potential antischistosomal activities.

Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to the existence of intermolecular interactions of hydrogen bond type (>N-H···O<) between the amide group (>N-H) of the LPSF/FZ4 and the ether group (-O-) of the polyethyleneglycol polymer, or the carbonyl (C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and thermal analysis of DSC. The solid dispersions with the polymer PVP, in higher concentrations, were revealed to be the best option to be used in the formulations of LPSF/FZ4 in both theoretical and experimental studies.

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Cyclodextrins (CDs) are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD used in the formulation in order to increase drug solubility and reduce dosage form volume.

Ciclodextrinas (CDs) são oligossacarídeos cíclicos, compostos por unidades D-glicopiranosídicas ligadas entre si por meio de ligações glicosídicas e sua principal propriedade está na capacidade de alterar as características físico-químicas e biológicas de fármacos com baixa solubilidade por meio da formação de complexos de inclusão fármaco:CD. Para a formação dos complexos de inclusão a molécula hospedeira necessita ajustar-se total ou parcialmente no interior da cavidade da CD, onde este ajuste está diretamente ligado a propriedades físico-químicas da molécula hóspede e hospedeira, facilidade de alojamento da molécula hóspede no interior da cavidade da CD, estequiometria, dose terapêutica e toxicidade. No entanto, as formas farmacêuticas podem atingir um elevado volume, em função da quantidade de CD requerida, sendo necessário aumentar sua eficiência de solubilização para que seja possível utilizar menores quantidades das mesmas. Isso pode ser obtido com a inclusão de pequenas quantidades de polímeros hidrossolúveis ao sistema. Nessa revisão, são abordados aspectos relacionados à complexação de fármacos com ciclodextrinas empregando-se polímeros hidrossolúveis para otimização da quantidade de CD utilizada na formulação, com a finalidade de aumentar a solubilidade do fármaco e reduzir o volume das preparações.

Estudos de mucoadesão no trato gastrointestinal para o aumento da biodisponibilidade oral de fármacos: [revisão] / Mucoadhesion studies in the gastrointestinal tract to increase oral drug bioavailability: [revision]

A biodisponibilidade oral de muitos fármacos é limitada pelo tempo de residência das formas farmacêuticas ao longo do trato gastrointestinal. A mucoadesão tem sido proposta como forma de prolongar o tempo de residência em determinada zona, contribuindo para o aumento do efeito terapêutico dos fármacos. O estômago e o intestino delgado têm sido preferencialmente os alvos de estudo da mucoadesão, tendo sido observados resultados promissores em ensaios in vitro. Contudo, alguns ensaios em humanos, usando a técnica de γ-cintigrafia, têm revelado o insucesso da mucoadesão como forma de aumentar o tempo de contacto de formulações no trato gastrointestinal superior. A falta de correlação in vitro/in vivo pode ser atribuída à complexidade do trato gastrointestinal humano. Muitos dos modelos in vitro reproduzem apenas em parte as condições observadas in vivo. Outros fatores, tais como a motilidade, o pH, a espessura e a taxa de renovação de muco, presença de enzimas e alimentos, não têm sido simulados em ensaios in vitro. A taxa de renovação do muco, a sensibilidade aos estímulos secretores e a motilidade são mais baixas no cólon que no estômago e intestino delgado. Portanto, a mucoadesão no cólon poderá constituir um conceito mais bem sucedido. Contudo, são necessários mais estudos quer em modelos animais quer em humanos para avaliar o seu verdadeiro potencial. Além disso, são necessários estudos de farmacocinética para determinar a libertação e posterior absorção do fármaco a partir do sistema mucoadesivo.

The oral bioavailability of many drugs can be limited by the residence time of pharmaceutical dosage forms in the gastrointestinal tract. Mucoadhesion has been proposed as a method to increase residence time at a specific area, hence increasing the therapeutic effect of drugs. Most research efforts on mucoadhesion have focused on the stomach and small intestine, with promising results observed from in in vitro studies. However, γ-scintigraphy data obtained in human studies have revealed the lack of success of mucoadhesion approaches in order to increase the contact time of formulations in the upper gut. The lack of in vitro/in vivo correlation can be attributed to the complex nature of the human gastrointestinal tract, with most in vitro models providing little resemblance to the in vivo situation, such as motility, pH, mucus thickness and mucus turnover, presence of enzymes and food. In the colon, the mucus turnover, the sensibility to mucus secretory stimulus and motility are lower than in the stomach and small intestine. Therefore, colonic mucoadhesion may be a more successful approach. Nevertheless, more studies in animals and humans are needed to evaluate its potential, as well as, pharmacokinetic studies to investigate drug release and absorption from mucoadhesive systems.

Sistemas farmacêuticos gastrorretentivos flutuantes / Pharmaceutical gastro-retentive systems

Freqüentemente recorre-se à produção de sistemas gastrorretentivos para modular a liberação de fármacos a partir de sistemas farmacêuticos com vistas ao aumento do tempo de permanência do fármaco no trato gastrointestinal. Umas das estratégias mais interessantes passa pela produção de sistemas flutuantes. Estes podem ser classificados em dois grupos: sistemas flutuantes efervescentes e sistemas flutuantes não-efervecentes. Neste artigo apresenta-se uma revisão bibliográfica do que tem sido produzido nesta área nos últimos anos.

Gastro-retentive systems are often produced in order to modulate drugs release from pharmaceutical forms and in this way to increase drug residence time in the gastrointestinal tract. One of the most interesting strategies consists in the preparation of floating devices. These can be classified into two groups: effervescent systems and non-effervescent systems. A review of what has been done in the last years is presented in this article.

Obtenção de pellets por extrusão e esferonização farmacêutica. Parte II: avaliação das características física de pellets / Production of pellets by pharmaceutical extrusion and spheronisation. Part II: physical characterisation of pellets

O processo de peletização, abordado na Parte I, consiste na aglomeração por via úmida de pós de uma substância ativa e excipientes sob a forma de unidades esféricas denominadas por pellets. Os pellets diferem de grânulos não apenas pela técnica utilizada para a produção, mas também no que respeita as características físicas conseguidas. O presente trabalho, o segundo de uma série de dois, apresenta uma revisão das características físicas e das técnicas para a caracterização física de pellets farmacêuticos abordando as principais necessidades posteriores a produção dessas multi-unidades, nomeadamente revestimento com película, enchimento de cápsulas, compressão, manuseamento, armazenamento e transporte.

The pelletisation process described in Part I consists of the wet agglomeration of fine powders of a drug substance and excipients into spherical units referred as pellets. Pellets differ from granules in terms of the production process and the physical characteristics. The current work, the second part of a series of two, intends to describe and revise the literature of the evaluation and characterisation of active drug pellets regarding the needs of postproduction of the units namely, film coating, capsule filling, compression, handling, storing and shiping.

Liberação específica de fármacos para administração no cólon por via oral. I - O cólon como local de liberação de fármacos / Colonic drug delivery. I- The colon as a site for drug delivery

A liberação específica de fármacos no cólon tem atraído a atenção de investigadores interessados no tratamento de patologias locais e no seu potencial na liberação de proteínas e peptídeos. O tratamento de patologias do cólon como é o caso da doença inflamatória do intestino pode ser otimizada com o recurso destes sistemas que se propõem a liberar o agente farmacológico adequado, seletivamente no local ativo de inflamação, na medida em que diminuem a dose oral e os seus efeitos adversos. A atividade das peptidases no cólon é muito baixa, o que torna possível que moléculas tão lábeis como as proteínas e peptídeos possam ser administrados oralmente sem comprometer a sua biodisponibilidade. Para desenvolver estes sistemas é fundamental entender completamente o cólon enquanto local de liberação de fármacos e, em particular, aspetos como o tempo de trânsito, pH e atividade enzimática do cólon que são a base dos mecanismos utilizados para iniciar a liberação de fármacos no cólon. Outro aspecto importante é a capacidade de absorção do cólon. Neste contexto, o extenso tempo de residência e a presença de barreiras químicas e biológicas podem, respectivamente, aumentar ou limitar a absorção de fármacos.O impacto da doença inflamatória do intestino na eficácia destes sistemas pode ter sido subestimado, na medida em que esta patologia pode alterar o pH e a actividade enzimática do cólon.

Drug delivery to the colon has become attractive to researchers interested in the treatment of local diseases and for its potential for the delivery of proteins and therapeutic peptides. The treatment of colonic disorders like the inflammatory bowel disease can be improved by the use of systems capable of delivering the appropriate pharmacological agent selectively in the active site of inflammation, because it reduces the oral dose and its systemic side effects. The activity of the peptidases in the colon is very low, which makes possible to such labile molecules like proteins and peptides to be orally administered, without compromising their bioavailability. In the development of these systems it is fundamental to fully understand the colon as a site for drug delivery and, in particular, aspects like transit time, pH and enzyme activity of the colon, which are the basic mechanisms used to trigger release of a drug in the colon. Another important aspect is the absorptive capacity of the colon. In this context, the long residence time and the presence of some biological and chemical barriers might, respectively, enhance or limit drug absorption. The impact of the active inflammatory bowel disease on the efficacy of the systems used for targeting drugs to the colon might have been underestimated, since this pathology can alter the colonic pH and the enzyme activity of the colon.

Liberação específica de fármacos no cólon por via oral. II - Tipos de sistemas utilizados / Colonic drug delivery. II- Types of delivery systems

Dois tipos de abordagens podem ser utilizadas para liberar fármacos no cólon: liberação retardada ou liberação específica no cólon. O primeiro caso diz respeito a formulações concebidas de forma a prolongar a dissolução do fármaco e a sua absorção, até que a formulação chegue ao cólon. Esta estratégia demonstra falta de especificidade quando comparada com outras que se baseiam nas características particulares do cólon. A liberação específica no cólon explora as suas propriedades como o pH, atividade enzimática e pressão intraluminal. No geral, o sistema ideal pode ser obtido com a utilização de peletes, que como é sabido possuem maior previsibilidade no seu esvaziamento gástrico e maior tempo de residência no cólon, ou sistemas revestidos com um design simples. Teoricamente, os sistemas baseados na atividade enzimática, e, sobretudo, os que são constituídos por polissacarídeos, são mais específicos e possuem baixa toxicidade. No entanto, qualquer outro sistema pode ser eficaz na liberação específica de fármacos no cólon. Na realidade, alguns sistemas tempo e pH dependentes comercializados, têm mostrado benefícios no tratamento da doença inflamatória do intestino, apesar da sua baixa especificidade. As investigações neste campo, devem ser conduzidas de forma a identificar a estratégia apropriada, que permita a liberação específica do fármaco de maneira segura, efetiva, pouco dispendiosa e com a mínima flutuação em termos de liberação de fármacos no local alvo.

Two basic approaches may be taken in delivering drugs to the colon: time-delayed release or colonic targeting. The former involves sustained release dosage forms, which are designed to prolong drug dissolution and hence absorption, until it reaches the colon. This strategy shows lack of specificity when compared with others that take advantage of unique characteristics present in the colon. Direct targeting involves the exploitation of environmental properties of the colon, like pH of the colon, enzymatic activity or intraluminal pressure. In general, the ideal colonic drug delivery may be accomplished by using pellets, which are known to have more predictable gastric emptying and great colonic residence times, and coated dosage forms with a simple design since they are easy to manufacture. Theoretically, the enzyme dependent systems, and, specially, those based in the use of polysaccharides, are more specific and non-toxic. Nevertheless, any of the others approaches might be suitable to obtain a colonic delivery system with the appropriate characteristics. Some commercially time-dependent and pH-dependent systems have shown important benefits in the treatment of inflammatory bowel disease, despite their less specificity. The investigations in this field should be conducted to identify the appropriate approach, which can result in the delivery of drugs in a safe, effective and less expensive manner with minimum fluctuation in terms of release of drug at target site.

Preparações radiofarmacêuticas e suas aplicações / Radiopharmaceuticals and applications

Os radiofármacos são compostos, sem ação farmacológica, que têm na sua composição um radionuclídeo e são utilizados em Medicina Nuclear para diagnóstico e terapia de várias doenças. Para aplicações de diagnóstico em Medicina Nuclear utilizam-se radiofármacos que apresentam na sua constituição radionuclídeos emissores de radiação g ou emissores de pósitrons (b+), já que o decaimento destes radionuclídeos dá origem a radiação eletromagnética penetrante, que consegue atravessar os tecidos e pode ser detectada externamente. Os radiofármacos para terapia devem incluir na sua composição um radionuclídeo emissor de partículas ionizantes (a , b- ou elétrons Auger), pois a sua ação se baseia na destruição seletiva de tecidos. Existem dois métodos tomográficos para aquisição de imagens em Medicina Nuclear: o SPECT (Tomografia Computarizada de Emissão de Fóton Único), que utiliza radionuclídeos emissores g (99mTc, 123I, 67Ga, 201Tl) e o PET (Tomografia por Emissão de Pósitrons), que usa radionuclídeos emissores de pósitrons ( 11C, 13N, 15O, 18F). Os radiofármacos podem ser classificados em radiofármacos de perfusão (ou 1ª geração) e radiofármacos específicos (ou 2ª geração). Os radiofármacos de perfusão são transportados no sangue e atingem o órgão alvo na proporção do fluxo sanguíneo. Os radiofármacos ditos específicos contêm molécula biologicamente ativa, que se liga a receptores celulares e que deve manter a sua bioespecificidade mesmo após ligação ao radionuclídeo. Assim, nestes radiofármacos, a fixação em tecidos ou órgãos é determinada pela capacidade da biomolécula de reconhecer receptores presentes nessas estruturas biológicas. As preparações radiofarmacêuticas são obtidas prontas para uso, em kits frios ou em preparações autólogas. De acordo com o tipo de preparação, existe um processo de controle de qualidade próprio. A maior parte dos radiofármacos em uso clínico corresponde a agentes de perfusão...

Radiopharmaceuticals are substances without pharmacological activity that are used in Nuclear Medicine for diagnosis and therapy for several diseases. Diagnosis radiopharmaceuticals generally emit g radiation or positrons (b+), because their decay originates penetrating electromagnetic radiation that can cross the tissues and be externally detected. Therapeutic radiopharmaceuticals must include in their composition ionized particles emission nucleus (a, b- or Auger electrons), since their action is based in selective tissue destruction. There are two main methods for image acquisition: SPECT (Single Photon Emission Computerized Tomography) that uses g emission radionuclides (99mTc, 123I, 67Ga, 201Tl) and PET (Positron Emission Tomography) that uses positron emission radionuclides like 11C, 13N, 15O, 18F. Radiopharmaceuticals can be classified into perfusion radiopharmaceuticals (first generation) or specific radiopharmaceuticals (second generation). Perfusion radiopharmaceuticals are transported in the blood e reach the target organ in the direct proportion of the blood stream. Specific radiopharmaceuticals contain a biologically active molecule that binds to cellular receptors that must remain biospecific after binding to the radiopharmaceutical. For this type of radiopharmaceuticals, tissue or organ uptake is determined by the biomolecule capacity of recognizing receptors in those biological structures. Radiopharmaceuticals are produced ready to use, in cold kits or in autologal preparations. According to the preparation type there is a different quality control procedure. Most of the radiopharmaceuticals used nowadays are of the perfusion type. Research focus in the development of specific radiopharmaceuticals that can provide information, at the molecular level, of biochemical alterations associated to different pathologies...

Complexos de inclusão de indometacina com hidroxipropil-beta-ciclodextrina: estudos de dissolução e coeficiente de partição / Inclusion compounds of indomethacin with hydroxypropyl-beta-cyclodextrin: dissolution profile and partition coefficient evaluation

A indometacina, antiinflamatório não-esteróide, é praticamente insolúvel em água. A hidroxipropil-beta-ciclodextrina confere aos fármacos nela incluídos melhores características de solubilidade. A formação de complexos com indometacina protege da hidrólise, aumentando a solubilidade. O objetivo desse trabalho foi estudar a influência da complexação por liofilização e por spray-dried, na dissolução e coeficiente de partição. Os resultados dos estudos de dissolução dos complexos de inclusão obtidos por liofilização quando comparados com os obtidos por spray-dryer, apresentam quer maior velocidade de dissolução quer melhor eficiência de dissolução. Os resultados da análise do coeficiente de partição, com ambos os métodos de complexação, confirmam a teoria de que são várias as forças intervenientes neste processo e não é só a fração livre de fármaco que condiciona o transporte para a fase orgânica, reforçando a importância do pH do meio. No estudo com o tampão fosfato pH 7,0, as variações no grau de transporte pela adição de ciclodextrina são muito pequenas, não ocorrendo alteração significativa dos valores de Log P*, verificando-se alterações mais significativas quando se utiliza o tampão fosfato pH 5,5. A complexação aumentou a capacidade de solubilização e dissolução da indometacina, a qual tem caráter lipófilo, sem alterar as características que lhe permitem ter boa capacidade de difusão através de membranas biológicas.

Aspectos biofarmacêuticos da formulação de medicamentos para neonatos. Fundamentos da complexação de indometacina com hidroxipropil-"beta"-ciclodextrina para tratamento oral do fechamento do canal arterial / Biopharmaceutical aspects of drugs formulations for neonatology. Rational for indomethacin's complexation with hydroxypropyl-

A terapêutica farmacológica em recém-nascidos confronta-se, por um lado, com um organismo sujeito a marcadas alterações biológicas, resultantes da composição orgânica e da maturação funcional, que decorre a diferentes graus em crianças com a mesma idade, determinando modificações no perfil farmacocinético e farmacodinâmico e, por outro lado, com a necessidade efetiva da utilização de fármacos. Para dar resposta à necessidade de tratamento destes doentes, recorre-se à utilização de medicamentos off label, sendo esta uma prática com um elevado risco de segurança e de eficácia, na ausência de informação acerca da estabilidade, solubilidade e biodisponibilidade...