Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine

Microemulsions (ME) containing soya phosphatidylcholine (SPC/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the proportions between the components to form clear systems. The dynamic light scattering results showed that the size of the oil droplets decreases significantly with the ratio of surfactant/oil phase added to system. Depending on the composition ME system could exhibit a thixotropic behavior. The apparent viscosity increased 25- and 13-folds with cholesterol concentration for drug-free and drug-load ME, respectively. It was also verified that the octanol/aqueous buffer partition coefficient (K-O/B) of doxorubicin (DOX) was pH dependent increasing abruptly above pH 6.0. It was possible to incorporate 2.24 mg/ml of DOX into ME. The incorporation of DOX in the ME systems increased the droplets size for all surfactant concentrations used in the system. The results suggest that DOX interacts with the microstructure of the ME at the studied pH increasing significantly the drug solubility. It was possible to conclude that the investigated ME can be a very promising vehicle as drug-carrier for administration of doxorubicin. (c) 2006 Elsevier B.V. All rights reserved.

CELULOSE FIBROSA DO BAGACO DA CANA-DE-ACUCAR - AVALIACAO DA ACAO AGLUTINANTE/DESAGREGANTE EM COMPRIMIDOS CONTENDO FARMACO HIDROSSOLUVEL

In this work, a fibrous cellulose obtained from the sugar cane bagasse was analysed about its binder/disintegrating action and about its interference degree in the dissolution rate ('in vitro') of active principles, when incorporated in a compact system that has a water-soluble drug. It was used as reference drug the Lithium Carbonate, considering its solubility in water and it difficulties in the compressibility and flow rate. That cellulose was evaluated in a comparative study, involving another fibrous cellulose generally used in the tablet obtainment (Microcel 3E-200). After the experiment in methodologies of dry granulation and wet granulation, it was concluded that the analysed celluloses presents adequate binder/disintegrating efficience and they are equivalents in these aspect.

Encapsulação da rifampicina em matrizes poliméricas flutuantes obtidas por liofilização a partir de metilcelulose e ftalato de hidroxipropilmetilcelulose. Avaliação da liberação in vitro

Floating multiparticles for oral administration with different compositions were studied from a matricial polymeric system to obtain sustained release. The polymers used in the multiparticles constitution were methylceullose (MC) and hydroxypropylmethylcelullose phthalate (HPMCP) in several proportions. Spherical and isolated structures were obtained using HPMCP/MC in the range from 1:3 to 1: 13. The diameters of the floating multiparticles were in the range from 3 to 3.25 mm, while the non-floating particles were between 1.75 and 2.1 mm. The morphological analysis by confocal microscopy showed that the probable mechanism of drug release was the diffusion from the inner of particles to external media. The encapsulation of hydrophilic model substances (tartrazin and bordeaux S), showed that the maximum incorporation was about 38%, while for the lipophilic model substances (rifampicin) was 45%. The in vitro release of rifampicin in acid medium was dependent on the ratio HPMCP/MC. In alkaline medium the release followed a two-step profile, with slow release in the initial times and subsequent increase in the higher times The initial drug delivery profile was not dependent on the MC/HPMCP ratio and can be related with the release of the antibiotic from multiparticle inner caused by the swelling of polymers by the presence of water in the system. However, afterwards the release proceeds with typical profile of process involving hydrogels systems.

Synthesis, characterization, and biological activity of a new palladium(II) complex with deoxyalliin

Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C6H10NO2S)2]. 13C NMR, 1H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. © 2005 NRC Canada.

A new insight about pharmaceutical dosage forms for benzathine penicillin G

In this work, a micellar system of benzathine penicillin G (BPG) in sodium deoxycholate (NaDC) was developed and evaluated physicochemically. The solubility profile of the drug in water and buffer solutions at various pH was determined, as well as its n-octanol/water partition coefficient. The Critical Micellar Concentration of NaDC and its ability to incorporate BPG were also assessed. The study was carried out at low and high ionic strength which was adjusted by the addition of sodium chloride. The results demonstrated the ability of the micellar system to incorporate BPG, as well as to increase its apparent solubility in water. The enhancement of the solubility of BPG by the presence of NaDC micelles could be analyzed quantitatively within the framework of the pseudo-phase model. Concentration analysis showed that the micellar system could attain up to 90% incorporation of BPG. The incorporated drug is expected to exhibit improved stability, since the antibiotic enclosed in the hydrophobic core of micelles is rather shielded from the aqueous external environment.

Preparação e caracterização inicial de complexo de inclusão entre nitrofurazona e 2-hidroxipropil-β-ciclodextrina

Nitrofurazone (NF), 5-nitro-2-furaldehyde semicarbazone, a broad-spectrum antibiotic, has reported toxic effects and low solubility in water. It would be of great interest to form inclusion complexes between NF and a cyclodextrin, to develop more effective and safer antibiotic formulations. This paper focuses on the preparation of inclusion complexes of NF with 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and their initial characterization by evaluating rates of complex formation, photostability, solubility isotherms, release rate profiles, stoichiometry of the complexes and their morphology, as revealed by scanning electron microscopy. The kinetic tests of complex formation revealed that 17,3 h is enough for stabilization of the NF-cyclodextrin complex. The solubility isotherm studies showed that the isotherm changes from type A to type B, as a function of temperature. The photostability experiments showed that the insertion of the NF in the HP-β-CD cavity protects the drug from photodecomposition. The release kinetic tests showed that the profile of NF release from the complex is altered by the presence of HP-β-CD in the medium. A Job's plot indicated that the stoichiometry of the complex was 1:1 NF:HP-β-CD. The scanning electron micrographs showed changes in the crystal structure of NF in the complex. This study focused on the physicochemical properties of drug-delivery formulations that could potentially be developed into a novel type of therapy with NF.

Influência das propriedades de granulados de celulose nas características físicas dos comprimidos

The compaction behavior of powdered solids can be strongly influenced by the physicochemical properties of excipients because they are frequently present in the tablet in larger amounts than the drug itself. The aim of this study was to assess the influence of the granule size of the cellulose on the physical characteristics of tablets produced in punches of different diameters, since this relation has never been explored in the literature. Granules of several sizes were produced by wet granulation and compressed in punches of various diameters by applying different forces. Size distribution, apparent density and flow of granules were assessed, as well as physical characteristics of the tablets (weight, hardness, friability and disintegration time). Reducing the granule size resulted in tablets of adequate crushing strength and fast disintegration; moreover, it allowed tablets to be produced without the need to use forces near the upper limit of the press, thus avoiding premature wear on the tabletting machine. Thus, once a suitable size for a given tablet formulation has been chosen, the granule size selected has been shown to determine the crushing strength of the tablet.

Alternativas para o tratamento da esquistossomose: Caracterizacao fisico-quimica do complexo de inclusao entre praziquantel e hidroxipropil-β-ciclodextrina

Praziquantel (PZQ) is the drug of choice commonly used for the treatment of shistosomiasis. However, it has low aqueous solubility, which could limit its bioavailability in the body. To circumvent these features, an inclusion complex with hydroxypropyl-beta- cyclodextrin (HP-β-CD) was prepared. Thus, the objective of this work was to prepare and characterize the PZQ/HP-β-CD inclusion complex. Morphological, spectroscopic, and calorimetric analysis showed the first signs of the guest/host interaction. The complexation kinetic analysis was used to determine the kinetic constant and, besides that, it was possible to establish the time consumed to reach equilibrium. Using the solubility isotherm, it was observed that the interaction with HP-β-CD increased 2.4 fold the aqueous solubility of plain PZQ. In vitro cytotoxicity tests, using fibroblast cells, evidenced no toxicity for these cells at the concentrations tested. These results demonstrated that there is a potential use of PZQ in formulations with HP-β-CD.

Estudo de perfil de dissolução dos medicamentos de referência, genérico e similar contendo cefalexina na forma farmacêutica cápsula

With recent advances in technology and research into drug delivery, the modernization of tests and greater emphasis on the predictability of therapeutic effect by means of in vitro tests, the dissolution test and the study of dissolution profiles are gaining more and more importance. Though introduced initially as a way of characterizing the release profile of poorly soluble drugs, dissolution tests are currently part of pharmacopoeial monographs on almost all the oral solid pharmaceutical forms. The objective of this study was to determine the dissolution profile (percent drug dissolved versus time) of the pioneer brand, generic and similar pharmaceutical capsules containing 500mg cephalexin. Three pharmaceutical brands (reference, generic and similar) were subjected to the dissolution test and in vitro dissolution profiles were recorded. From the results of the dissolution test, it was concluded that the samples met the acceptance criterion, as no difference was observed in the percentage of the drug dissolved in a standard time. The dissolution profile indicated that this medicine, in this pharmaceutical form, dissolves readily (85% of the drug dissolved in 15 minutes) and the curves showed great similarity, suggesting that the 3 brands are pharmaceutically equivalent.

Kinetic parameters for thermal decomposition of supramolecular polymers derived from diclofenac-meglumine supramolecular adducts

Meglumine is an aminocarbohydrate able to form supramolecular adducts with organic acids. The recognition is based on hydrogen bonds and the structures resulting from the complexation have high solubility in water. This property has been exploited by the pharmaceutical industry in the improvement of existing drugs, and the successful example of this approach involves the poorly soluble non-steroidal anti-inflammatory drugs (NSAIDs). Investigation of the thermal behavior of adduct obtained from meglumine and the NSAID diclofenac revealed that a polymer-like material is formed from the self-assembly of diclofenac-meglumine adducts in the melt. This polymer showed a high molecular weight around 2.0×105kDa. The kinetic parameters for the thermal decomposition step of the polymer were determined by the Capela-Ribeiro non-linear isoconversional method. From data for the TG curves in nitrogen atmosphere and heating rates of 5, 10, 15 and 20°Cmin-1, the Eα and Bα terms could be determined, and consequently the pre-exponential factor, Aα, as well as the kinetic model, g(α). © 2012 Elsevier B.V.