Equilibrium solubility versus intrinsic dissolution: characterization of lamivudine, stavudine and zidovudine for BCS classification

Solubility and dissolution rate of drugs are of major importance in pre-formulation studies of pharmaceutical dosage forms. The solubility improvement allows the drugs to be potential biowaiver candidates and may be a good way to develop more dose-efficient formulations. Solubility behaviour of lamivudine, stavudine and zidovudine in individual solvents (under pH range of 1.2 to 7.5) was studied by equilibrium solubility and intrinsic dissolution methods. In solubility study by equilibrium method (shake-flask technique), known amounts of drug were added in each media until to reach saturation and the mixture was subjected to agitation of 150 rpm for 72 hours at 37 ºC. In intrinsic dissolution test, known amount of each drug was compressed in the matrix of Wood's apparatus and subjected to dissolution in each media with agitation of 50 rpm at 37 ºC. In solubility by equilibrium method, lamivudine and zidovudine can be considered as highly soluble drugs. Although stavudine present high solubility in pH 4.5, 6.8, 7.5 and water, the solubility determination in pH 1.2 was not possible due stability problems. Regarding to intrinsic dissolution, lamivudine and stavudine present high speed of dissolution. Considering a boundary value presented by Yu and colleagues (2004), all drugs studied present high solubility characteristics in intrinsic dissolution method. Based on the obtained results, intrinsic dissolution seems to be superior for solubility studies as an alternative method for biopharmaceutical classification purposes

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Variação sazonal na alelopatia de extratos aquosos de Coleus barbatus (A.) Benth. sobre a germinação e o desenvolvimento de Lactuca sativa L. Seasonal variation in the allelopathy of aqueous extracts from Coleus barbatus (A.) Benth. on the germination and development of Lactuca sativa L.

O objetivo deste trabalho foi avaliar o efeito alelopático de extratos de Coleus barbatus sobre a germinação e desenvolvimento de plântulas de alface. Os experimentos foram conduzidos em laboratório, em diferentes concentrações de extratos obtidos de folhas de falso-boldo (0; 7,5; 15; 22,5; 30%), coletadas nas quatro estações do ano, obtidos por trituração, maceração, infusão e decocção. As sementes de alface foram distribuídas sobre placas de petri umidecidas com 10 mL de solução. Os resultados mostraram que os extratos de folhas afetaram a germinabilidade de sementes de alface apenas na concentração de 30% do extrato preparado por decocção de folhas coletadas no inverno. O índice de velocidade de germinação apresentou redução significativa nos extratos triturados preparados no outono e inverno; na maceração de folhas coletadas no verão e outono e no extrato de decocção preparado no inverno. Os extratos estimularam o crescimento da parte aérea das plântulas de alface, ao passo que, o comprimento das raízes foi afetado pelos extratos, ora inibindo, ora estimulando o crescimento das mesmas. Os extratos de folhas de falso-boldo coletadas nas quatro estações do ano apresentaram efeito alelopático sobre a germinação e o desenvolvimento da alface, sendo que estes variaram em função da sazonalidade da coleta, da forma de obtenção dos extratos e das concentrações testadas.<br>The aim of this study was to evaluate the allelopathic effects of extracts from Coleus barbatus on germination and seedling growth of lettuce. The experiments were conducted in the laboratory using different concentrations (0, 7.5, 15, 22.5, 30%) of aqueous extracts from "falso-boldo" leaves harvested in all four seasons; extracts were obtained by grinding, maceration, infusion and decoction. Seeds were distributed on Petri dishes moistened with 10 mL solution. Results showed that the leaf extracts affected the germination of lettuce seeds only at the concentration of 30% extract prepared by decoction of leaves harvested in the winter. Germination speed index showed significant reduction for ground extracts prepared in the fall and winter, as well as for macerated leaves harvested in the summer and fall and for extracts prepared through decoction in the winter. The extracts stimulated the growth of shoots of lettuce seedlings, whereas root length was affected by the extracts, which either stimulated or inhibited its growth. Extracts of "falso-boldo" leaves harvested in all four seasons had allelopathic effect on germination and development of lettuce, and the latter varied depending on the harvest season, the form of preparing the extracts and the tested concentrations

Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

ABSTRACT This study aimed to improve the water solubility of amiodarone hydrochloride (AMH) via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms

Amiodarone hydrochloride: enhancement of solubility and dissolution rate by solid dispersion technique

abstract Amiodarone HCl is an antiarrhythmic agent, which has low aqueous solubility and presents absorption problems. This study aimed to develop inclusion complexes containing hydrophilic carriers PEG 1500, 4000 and 6000 by fusion and kneading methods in order to evaluate the increase in solubility and dissolution rate of amiodarone HCl. The solid dispersion and physical mixtures were characterized by X-ray diffraction, FT-IR spectra, water solubility and dissolution profiles. Both methods and carriers increased the solubility of drug, however PEG 6000 enhanced the drug solubility in solid dispersion better than other carriers. Different media were evaluated for the solubility study, including distilled water, acid buffer pH 1.2, acetate buffer pH 4.5 and phosphate buffer pH 6.8 at 37 ºC. Based on the evaluation of the results obtained in the study phase solubility carriers PEG 4000 and PEG 6000 were selected for the preparation of the physical mixture and solid dispersion. All formulations were prepared at drug-carrier ratios of 1:1 to 1:10(w/w). The results of in vitro release studies indicated that the solid dispersion technique by fusion method in proportion of 1:10 (w/w) increased significantly the dissolution rate of the drug. X-ray diffraction studies showed reduced drug crystallinity in the solid dispersions. FT-IR demonstrated interactions between the drug and polymers