A new approach to the granulation of beta-cyclodextrin inclusion complexes

Cyclodextrins (CDs) are annular oligosaccharides containing 6-12 glucose unities joined together by alpha-1,4 bonds. They have a conical-truncated shape with a lipophilic cavity in which different molecules can be included resulting in a stable inclusion complex. The cyclodextrins have been widely applied in pharmaceutical technology with the objective of increasing the solubility, stability and bioavailability of drugs in different pharmaceutical dosage forms, such as tablets. In order to obtain beta-CD tablets, liquid dispersions of drug/beta-CD are usually submitted to different drying processes, like spray-drying, freeze-drying or slow evaporation, being this dry material added to a number of excipients. However, such drying processes can generate particulate materials showing problems of flow and compressibility, needing their conversion into granulates by means of wetting with granulation liquid followed by additional drying. In this work, the main objective was to evaluate the preparation of tablets without the need of this additional drying step. For this purpose an aqueous dispersion containing acetaminophen/beta-CD complex and cornstarch was dried using a spouted bed and the obtained granules were compressed in tablets. Acetaminophen was used as model drug due to its low water solubility and the inexpensive and widely available cornstarch was chosen as excipient. Acetaminophen powder was added into a beta-cyclodextrin solution prepared in distilled water at 70 degrees C. Stirring was kept until this dispersion cooled to room temperature. Then cornstarch was added and the resulting dispersion was dried in spouted bed equipment. This material was compressed into tablets using an Erweka Korsh EKO tablet machine. This innovative approach allowed the tablets preparation process to be carried out with fewer steps and represents a technological reliable strategy to produce beta-cyclodextrin inclusion complexes tablets. (C) 2010 Elsevier By. All rights reserved.

Interference of the blood clot on granulation tissue formation after tooth extraction. Histomorphological study in rats.

The interference of a blood clot in the first postoperative hours of dental extraction wounds was studied in rats. Sixty male albino rats were divided into two groups: Group I, immediately after extraction of right maxillary incisor the gingival mucosa was approximated and sutured; Group II, after 6 to 8 minutes postoperatively the blood clot was removed with saline irrigation and absorbent paper cones. The mucosa was then approximated and sutured. Six animals in each group were sacrificed after 12 hours, 1, 4, 7 and 10 days. There was a profound delay in healing in Group II since, although a new blood clot was later formed, it was not organized. The quality and the constitution, maintenance and retraction of the clot are the regulating factors in connective tissue formation during alveolar healing.

The changes on microstructure and electrical properties of Bi:2223/Ag composite as a function of the granulation and the content of the added silver powder

The Bi-Sr-Ca-Cu-O system has been one of the most studied superconducting ceramic materials for industry applications. The most of the studies with this aim are on silver/ceramic composites, due to the benefits and great compatibility of this metal with the oxide. In this paper we describe a systematic and comparative study on Ag/BSCCO composite, made by the citrate route, in which the ceramic pellets are sintered in the presence of silver powder using several proportions and having several granulations. It was observed that the introduction of fine (0.5 and 2 μm) silver powder in the proportions of 5 wt. % always implies in a better critical current density compared to the no silver pellet. According to the results, the silver powder in excess of 5 wt.% may not promote best electrical properties, depending on the size of the silver particles.

Reparação de feridas cutâneas de roedores da espécie Calomys callosus, tratadas com hidrocarboneto alifático: aspectos morfométricos, morfológicos e histológicos

O efeito cicatrizante do hidrocarboneto alifático foi pesquisado através da aplicação diária em feridas cutâneas, cirurgicamente provocadas, em roedores da espécie Calomys callosus. As feridas dos animais foram analisadas sob os aspectos macroscópicos e histológicos transcorridos 3, 7, 14 e 21 dias de tratamento e comparado com o uso de solução fisiológica a 0,9%. O hidrocarboneto alifático antecipou a cicatrização ao diminuir a umidade, aumentar a formação do tecido de granulação e a neovascularização, conduzindo à reepitelização.

Pitiose cutânea equina de localização atípica tratada topicamente com solução de anfotericina B e DMSO

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdomen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes.Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated as initial treatment, and due to financial reasons, the owners elected only the topical antifungal therapy to control the fungus infection after surgery. Flunixin meglumine was also administrated for five days aiming the control of pain and inflammation. The wound was cleaned with povidone-iodine solution and rinsed with a solution containing, 50 mg, of amphotericin B in 10 mL of sterile water and 10 mL of DMSO. This procedure was carried Out twice a day. The wound healed fast due to an excellent centripetal epithelialization. and the horse was discharged after 64 days showing only 5% of the initial wound area. The owner reported by telephone the complete healing and hair growth 10 days after discharge.Discussion: Despite the atypical location of the tumoral lesion described at the present report, the history and clinical manifestations, especially the intense pruritus, showed similarity with other characteristic reports of equine cutaneous pythiosis. The diagnosis was confirmed by the histopathological examination showing hyphae structures, as described to be evidences of the presence of Pythium insidiosum in the tissue. The surgical procedure was the first step to provide remission of clinical signs, and one day after surgery the pruritus desapeared. After excision of the granulomatous tissue and cauterization, daily topical administration of amphotericin B associated with DMSO was effective in destroying the infectious agent, as observed by the excellent epithelization. A pink granulation tissue grew up providing an ideal surface for epithelial migration and the healing process progressed quickly. Centripetal epithelialization reduced the wound area until 3% of the initial area in 64 days of treatment, when the remaining wound was found almost completely healed and covered with hair. At the present report, the horse presenting pythiosis was only topically treated. The recommended therapy using amphotericin B and DMSO solution was effective, economically viable and low risk, considering that the systemic antifungal therapy usually suggested is expensive and extremely nephrotoxic. The atypical location of the lesion on the left flank shows that any anatomical region can be affected by the fungus, since the conditions for its development were present.

Efeito da concentração do amido de milho na liberação de paracetamol de comprimidos

Este trabalho avaliou a influência da concentração de amido de milho nas características físicas e na liberação in vitro de paracetamol a partir de comprimidos. Os granulados foram analisados quanto à granulometria e densidades aparentes bruta e compactada e os comprimidos quanto ao peso médio, espessura, dureza, friabilidade, tempo de desintegração. Os comprimidos foram preparados a partir de granulados obtidos por granulação a úmido, utilizando cozimento de amido a 10% como agente granulante, segundo três formulações. Embora os comprimidos obtidos tenham apresentado características dentro dos limites farmacopéicos, os resultados indicam que variações da concentração de amido provocam diferenças nos diversos parâmetros físicos estudados. Concentração mais alta de amido em pó dá origem, provavelmente, à interação entre os componentes da fórmula, interferindo na liberação in vitro do fármaco. Isto demonstra a importância de se otimizar a concentração dos adjuvantes numa formulação de comprimidos, pois, embora uma pequena variação nesta concentração não exerça efeito significativo no tempo de desintegração, a quantidade de fármaco liberado pode ser substancialmente alterada.

Treatment of venous ulcers with fibrin sealant derived from snake venom

Venous ulcers of the lower limbs complicated by infection or chronicity represent a serious public health problem. The elevated number of those afflicted burdens the health services, interferes in quality of life and causes absenteeism. Although there are 2,500 items on the market, ranging from the simplest dressing up to the most complex types of dressing, treatment remains a challenge. Among the substances used, fibrin sealant is the one that promotes diminution of bacterial colonization and of edema, controls hemorrhaging, alters the pain threshold by protecting the nerve endings, hydrates the wound bed and forms granulation tissue that favors healing. Its disadvantages include higher cost and utilization of human fibrinogen that can transmit infectious diseases. The Center for the Study of Venoms and Venomous Animals (CEVAP) at São Paulo State University (UNESP) developed a new sealant made up of fibrinogen extracted from large animals and from an enzyme obtained from snake venom. The present study, developed in the Health Education Clinic (CEPS) of Sacred Heart University (USC) aimed to evaluate the effect of the new sealant on the healing process of venous ulcers in 24 adult patients, seven of whom were male and 17 female. Two study groups were formed as follows: Group 1 (G1) - control group of 11 patients treated with essential fatty acid (EFA) and Unna's boot, and Group 2 (G2) - 13 patients treated with essential fatty acid (EFA), fibrin sealant and Unna's boot. The follow-up lasted eight weeks and the sealant was applied at only the first and fourth weeks. The results showed that Group 2 presented worse lesion conditions as to healing, but, when comparing the two groups, it was noteworthy that the the sealant was effective in healing venous ulcers. There is evidence that the new sealant is recommended for leg ulcers with the following advantages: ease of application, preparation of the wound bed, diminution of pain and a higher number of discharges in the eighth week. More important, other positive characteristics are non-transmission of infectious diseases, absence of adverse reactions, and economic advantage of being produced by Brazilian technology. Finally, it is suggested that the weekly application of sealant, for at least eight weeks, could improve the healing process and consequently life quality.

Repair of the anophthalmic cavity of rats with synthetic hydroxyapatite

We placed spheres of synthetic hydroxyapatite (calcium chloride combined with sodium phosphate) in the eviscerated or enucleated orbital cavity of rats in order to evaluate the biocompatibility of this material with the orbital cavity. The study was conducted on 50 albino rats, 25 of which were submitted to enucleation and 25 to evisceration of one eye. The animals were sacrificed 7, 15, 21, 30 and 60 days after surgery and the orbital content was submitted to histopathological examination. A reaction of the young granulation tissue type was observed first. The hydroxyapatite was gradually surrounded by a granulomatous macrophage inflammatory response and covered with dense connective tissue that formed a sort of mesh septating and supporting progressively smaller blocks of the substance. The same type of reaction was observed in the enucleated and eviscerated cavities. We conclude that synthetic hydroxyapatite is an inert nonallergenic material which is appropriate for volume replacement in the anophthalmic cavity

Influence of ovariectomy on healing of autogenous bone block grafts in the mandible: A histomorphometric study in an aged rat model

Purpose: The aim of this study was to evaluate quantitatively and qualitatively the influence of estrogen deficiency on autogenous bone block grafts in aged variectomized rats. Materials and Methods: Fifty 12-month-old female Wistar rats were used in the study. They were divided into 2 groups, an ovariectomized group and a sham-operated group. After 30 days the animals received autogenous block bone grafts on the angle of the mandible, harvested from the calvaria. The animals were euthanized at 7, 14, or 28 days postoperatively. Results: Histologic analysis showed that at 7 days postsurgery, the interface between graft and recipient site in the sham-operated group appeared filled by a granulation tissue with angiogenic activity, whereas the ovariectomized group still exhibited a blood clot and a granulation tissue in organization. on the 14th postoperative day, the interface in the shamoperated group was partially filled by newly formed bone establishing a union between the graft and the recipient site. The interface in the ovariectomized group was typically filled by granulation tissue with discrete osteogenic activity in most specimens. on the 28th postoperative day, the graft in the sham-operated group appeared histologically integrated to the mandible. However, the interface in the ovariectomized group appeared partially filled by newly formed bone, with areas of interposed connective tissue. The statistical analysis revealed that bone neoformation was significantly greater in the sham-operated group (57.41% at 14 days and 68.35 at 28 days) in comparison with the ovariectomized group (40.82% at 14 days and 53.09 at 28 days) at the 5% level. Conclusion: The estrogen depletion caused by the ovariectomy hindered the healing process of autogenous block bone grafts placed in the mandibles of aged rats.

Rat tissue reaction to MTA FILLAPEX (R)

The aim of this study was to evaluate the rat subcutaneous tissue reaction to implanted polyethylene tubes filled with mineral trioxide aggregate (MTA) FILLAPEX (R) compared to the reaction to tubes filled with Sealapex (R) or Angelus MTA (R). These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7, 15, 30, 60, and 90 days. The specimens were stained with hematoxylin and eosin or Von Kossa or left unstained for examination under polarized light. Qualitative and quantitative evaluations of the reaction were performed. All materials caused moderate reactions after 7 days, which decreased with time. The reactions were moderate and similar to that evoked by the control and Sealapex (R) on the 15th day. MTA FILLAPEX (R) and Angelus MTA caused mild reactions beginning after 15 days. Mineralization and granulation birefringent to polarized light were observed with all materials. It was concluded that MTA FILLAPEX (R) was biocompatible and stimulated mineralization.

Processo de reparo em feridas de extração dentária em camundongos tratados com o complexo Symphytum officinale e Calendula officinallis

Medicamentos homeopáticos como o Symphytum officinalle e a Calendula officinallis são dotados de propriedades anti-sépticas, antiinflamatória, cicatrizantes e também agem como promotores da consolidação de fraturas ósseas. Neste trabalho, uniram-se esses dois medicamentos similares em um complexo para verificar o seu efeito no reparo em feridas de extração dentária em camundongos. O complexo Symphytum officinalle e Calendula officinallis nas potências de 6CH e 3CH, respectivamente, foi ministrado por via oral ao grupo tratado durante 5 dias antes e após a extração do incisivo superior direito. No grupo controle, administraram-se 5ml de álcool etílico a 70% diluídos em 30 ml de soro fisiológico. Após a proservação, os animais foram sacrificados, a maxila direita separada da esquerda, fixada e processada para inclusão em parafina. Após a microtomia, os cortes obtidos foram corados pela H/E. A análise histológica mostrou que, tanto no grupo controle como no tratado, o alvéolo dentário estava preenchido por tecido de granulação e tecido ósseo neoformado, com graus variáveis de maturação, rico em osteócitos. No entanto, nos animais tratados, o processo de reparo em feridas após extração dentária do incisivo superior direito mostrou um avanço progressivo de neoformação óssea mais acentuado quando comparado ao grupo controle, em tempos equivalentes. Estes resultados enfatizam as propriedades biológicas do complexo Symphytum officinalle e Calendula officinallis e sua possível utilização como recurso terapêutico na Odontologia.

V2O5/TiO2 catalyst xerogels: Method of preparation and characterization

This work describes a modified sol-gel method for the preparation of V2O5/TiO2 catalysts. The samples have been characterized by N-2 adsorption at 77 K, X-ray Diffractometry (XRD), Scanning Electronic Microscopy (SEM/EDX) and Fourier Transform Infrared Spectroscopy (FT-IR). The surface area increases with the vanadia loading from 24 m(2) g(-1) for pure TiO2 to 87 m(2) g(-1) for 9 wt% of V2O5. The rutile form is predominant for pure TiO2 but becomes enriched with anatase phase when vanadia loading is increased. No crystalline V2O5 phase was observed in the diffractograms of the catalysts. Analysis by SEM showed heterogeneous granulation of particles with high vanadium dispersion. Two species of surface vanadium were observed by FT-IR spectroscopy: a monomeric vanadyl and polymeric vanadates. The vanadyl/vanadate ratio remains practically constant. Ethanol oxidation was used as a catalytic test in a temperature range from 350 to 560 K. The catalytic activity starts around 380 K. For the sample with 9 wt% of vanadia, the conversion of ethanol into acetaldehyde as the main product was approximately 90% at 473 K.

Presence of calcium in oocytes of the diplopod Rhinocricus padbergi Verhoeff (Spirobolida, Rhinocricidae)

In diplopods, the presence of calcium-containing structures seems to be a common finding in some species, with its formation being similar to that observed for other intracellular mineralization systems. In the present study, using histochemistry and transmission electron microscopy, a large amount of calcium was observed in the oocytes of Rhinocricus padbergi. Calcium was detected in both less and well developed oocytes, i.e., the occurrence of calcium coincided with the beginning of vitellogenesis. Calcium was observed as fine granulation distributed within the cytoplasm or deposited in spherical structures apparently formed by overlapping calcium layers. Some authors have suggested that these structures represent a type of reserve used for the calcification of the embryo exoskeleton, whereas others believe that calcium inclusions are a mechanism of organism detoxification as a result of excess calcium ingested by animals during soil turnover. We suggest in this paper that the first hypothesis could be occurring in R. padbergi since at the juvenile stages of the individuals the uptake of calcium is low and because the oocyte is a specialized cell not associated with detoxification.

Accessory Nuclei in the Oocytes of Pachycondyla (Neoponera) villosa (Hymenoptera: Ponerinae) as a Source of Annulate Lamellae

In insects' oocytes, structures called accessory nuclei can be observed. They are similar to the nucleus of the oocyte and have been detected in Hymenoptera as well as in other groups, with their source and functions still under discussion (Cassidy & King 1972). Through the use of histochemical techniques as well as ultrastructural ones, it was possible to observe several accessory nuclei surrounding the oocyte nucleus in the immature oocytes of Pachycondyla (Neoponera) villosa ants. Morphologically they were seen to be round and smaller than the germinal vesicle. When using these histochemical techniques, the only positive reaction was for proteins. Ultrastructurally they have the same morphology as the oocyte nucleus and a fine and electrondense granulation was observed inside them. The function of accessory nuclei in P (Neoponera) villosa is probably as a source of anullate lamellae and as an RNA reservoir in the oocytes. In mature oocytes (stage III), these structures are not observed, suggesting that they disappeared before this stage by releasing their contents into the oocytes' cytoplasm, according to Camargo-Mathias and Caetano (1993).