Lapsille ex tempore -valmistettavien varfariini- ja spironolaktonikapseleiden annosvaihtelu ja säilyvyysseuranta

There aren't always available suitable authorized drug products for different age and different weight pediatric patients. Hospital pharmacies have to prepare suitable doses and dosage form for these very young patients extemporaneously. In Finland oral powders are usually used in pediatric medication. In previous studies it has been found that part of drug dose sticks to paper of oral powder and the patient doesn't get the entire intended dose. It is suggested that hard capsules may be better dosage form than oral powders, because capsules have smaller area than oral powders, where the powder can stick. The aim of this study was to examine, whether warfarin- and spironolactone capsules prepared by hospital pharmacy meet European Pharmacopeia standards of uniformity of content. Capsules were compounded from commercial tablets and capsulated by Feton-capsulating device. In this study capsules manufactured with automatic capsule filling device attached to analytical balance, oral powders and capsules prepared from pure drug substance were also compared to capsules compounded from tablets. The three month stability of compounded capsules was also examined. In hospital pharmacy many different strengths are compounded from same drug substance, ordered by physician. Ordered strengths can be nearly identical, but whether the small differences in concentration can possibly be prepared in hospital pharmacy is unknown. From both drug substances two strengths with small difference in concentration were prepared and it was studied if statistically significant difference exists. The drug concentrations of preparations were measured by high performance chromatography (HPLC). Aqualab-water activity meter was used to study water activity of samples during the stability testing. Content uniformities of all capsule batches complied with test specified in the European Pharmacopeia.The drug concentrations of capsules were significantly lower than target concentrations. With these drug substances no difference, between the drug concentration of oral powder and capsules, was found. According to this study oral powders can be replaced by capsules. Warfarin and spironolactone capsules remain at least three months, when storaged in room temperature. Warfarin capsules can be prepared accuracy of 0,1 mg and spironolactone capsules accuracy of 0,5 mg.Eri-ikäisille ja -painoisille lapsille ei ole aina saatavilla sopivia kaupallisia lääkevalmisteita. Sairaalaapteekeissa joudutaan valmistamaan näille nuorille potilaille sopivia annoksia ja lääkemuotoja ex tempore -valmistuksena. Suomessa lasten lääkintään on käytetty perinteisesti annosjauheita. Tutkimuksissa on kuitenkin havaittu, että osa lääkeaineesta tarttuu kiinni annosjauhekuoreen, eikä potilas saa kaikkea hänelle tarkoitettusta annoksesta. Annosjauheita paremmaksi lääkemuodoksi on ehdotettu kovia kapseleita, joihin pienemmän pinta-alan takia tarttuu vähemmän lääkeainetta. Tämän tutkimuksen tarkoituksena oli tutkia täyttävätkö sairaala-apteekissa valmistetut Fetonkapselointilaitteella valmistetut varfariini- ja spironolaktonikapselit Euroopan farmakopean annosvaihtelutestin vaatimukset. Tutkimuksessa verrattiin myös analyysivaakaan liitettävällä Quantoskapselointilaitteella valmistettujen kapseleiden, annosjauheiden ja puhtaasta lääkeaineesta valmistettujen kapseleiden keskimääräistä lääkeainepitoisuutta ja annosvaihtelua Feton-laitteella kapseloitujen kapseleiden vastaaviin arvoihin. Lisäksi tutkittiin kapseleiden kolmen kuukauden säilyvyys. Sairaala-apteekissa valmistetaan samasta lääkeaineesta useita eri vahvuuksia lääkärin määräyksen mukaan. Tilatut vahvuudet voivat olla hyvin lähellä toisiaan, mutta tietoa kuinka hyvin pieniä pitoisuuseroja pystytään sairaala-apteekissa valmistamaan, ei ole ollut saatavilla. Kummastakin lääkeaineesta valmistettiin kaksi toisiaan lähellä olevaa pitoisuutta ja tutkittiin eroavatko ne tilastollisesti merkittävästi toisistaan. Valmisteiden lääkeainepitoisuudet tutkittiin korkean erotuskyvyn kromatografialla (HPLC). Näytteiden vesiaktiivisuuden muuttumisen tutkimiseen käytettiin Aqualab-vesiaktiivisuusmittaria. Kaikki kapselierät täyttivät Euroopan farmakopean annosvaihtelutestin vaatimukset. Kapseleiden lääkeainepitoisuuden havaittiin kuitenkin olevan tavoitepitoisuutta huomattavasti pienempi. Annosjauheiden ja kapseleiden lääkeainepitoisuuksissa ei näillä lääkeaineilla havaittu olevan juurikaan eroa, joten annosjauheiden korvaaminen kapseleilla on mahdollista. Varfariini- ja spironolaktonikapselit säilyivät huoneenlämmössä kolmen kuukauden ajan. Varfariinikapseleiden valmistaminen 0,1 mg ja spironolaktonikapseleiden valmistaminen 0,5 mg pitoisuuserolla oli mahdollista

Production of container-grown nursery plants on capillary sand beds

This study investigated the effect of growth medium on the growth of nursery plants in a capillary irrigation system, the use and amount of slow-release fertilizer for the fertilization of container-grown nursery plants, and the need fora base dressing with a slow release fertilizer. Also investigated were the effect of different concentrations of alkyl aryl trimethyl ammonium chloride solution (Gloquat C) in preventing rooting through, and the use of a watering control device based on measuring radiation energy in field conditions. The experiments on growth medium revealed that all the growth media included in the experiment, i.e. sphagnum peat, peat/rock wool mixture (1 : 1),or peat/sand mixture (3 : 1), can be used for container-grown nursery plants if a base dressing is used with Nutricote(70), a slow-release fertilizer. The effect of slow-release fertilizer was better in peat mixtures, and this effect was especially clear when no base dressing was used. The use of slow-release fertilizer proved to be a good fertilization method in a capillary irrigation system. The fertilizing effect of Nutricote (70) given in the spring lasted until early June of the following year. Nutricote(70) was found to need a base fertilizer dressing. Abase dressing of 1.2 kg/m3 of a compound fertilizer (Turpeen Y-lannos; N 11 % P 10.5 %, K 18.3 %) with 1.5 kg/m3 of slow release fertilizer proved to be a suitable fertilization method for ornamental woody nursery plants in a capillary irrigation system. The tallest plants were obtained with a base dressing that was mixed with 3 kg/m3 of the slow-release fertilizer. Plants thus fertilized were, however, considered to be too large for transport and handling. The problem of a secondary root ball under the pot in sand beds was prevented by spreading 15 ml/m2 of Gloquat C on the sand surface. The capillary irrigation system and the automatic irrigation control worked well in experiments carried out under practical conditions. The potted nursery plants were kept evenly moist, and the plants grew to market size in one growing season

Parallel solution of nonlinear contingency- constrained network problems

Abstract This paper presents a nonlinear stochastic programming formulation for a large-scale contingency-constrained optimal power flow problem. Using a rectangular IV formulation to model AC power flow in the transmission network, we construct a nonlinear, multi-scenario optimization formulation where each scenario considers failure an individual transmission element. Given the number of potential failures in the network, these problems are very large; yet need to be solved rapidly. In this paper, we demonstrate that this multi-scenario problem can be solved quickly using a parallel decomposition approach based on nonlinear interior-point methods. Parallel and serial timing results are shown using a test example from Matpower, a MATLAB-based framework for power flow

Multiagent cooperation for solving global optimization problems: an extendible framework with example cooperation strategies

This paper proposes the use of multiagent cooperation for solving global optimization problems through the introduction of a new multiagent environment, MANGO. The strength of the environment lays in itsflexible structure based on communicating software agents that attempt to solve a problem cooperatively. This structure allows the execution of a wide range of global optimization algorithms described as a set of interacting operations. At one extreme, MANGO welcomes an individual non-cooperating agent, which is basically the traditional way of solving a global optimization problem. At the other extreme, autonomous agents existing in the environment cooperate as they see fit during run time. We explain the development and communication tools provided in the environment as well as examples of agent realizations and cooperation scenarios. We also show how the multiagent structure is more effective than having a single nonlinear optimization algorithm with randomly selected initial points

Evolution of Biocatalysis at Novartis over the last 40 Years

The fortieth anniversary of biocatalysis started at Ciba-Geigy and later at Novartis is a great time to pause and reflect on development of science and technology in this field. Enzyme-based synthesis became a highly valued enabling tool for pharmaceutical research and development over the last decades. In this perspective we aim to discuss how the scientific approaches and trends evolved over the time and present future challenges and opportunities

Challenge of paediatric compounding to solid dosage forms sachets and hard capsules - Finnish perspective

Objectives The study evaluated the quality of compounded sachets and hard gelatine capsules and their feasibility in paediatric drug administration. Methods Commercial tablets were compounded to sachets and capsules in hospital environment, and the uniformity of content and simulated drug dose were determined. Key findings Compounded formulations were successfully obtained for a range of drug substances; dipyridamole, spironolactone, warfarin and sotalol formulations were within acceptable limits for uniformity of content, in most cases. However, some loss of drug was seen. The type and amount of excipients were found to affect uniformity of content; good conformity of capsules was obtained using lactose monohydrate as filler, whereas microcrystalline cellulose was a better choice in sachets. In capsules, content uniformity was obtained for a range of drug doses. If the drug is aimed to be administered through a nasogastric tube, solubility of the drug and excipients should be considered, as they were found to affect the simulated drug dose in administration. Conclusions Compounded sachets and capsules fulfilled the quality requirements in most cases. In compounding, the choice of excipients should be considered as they can affect conformity of the dosage form or its usability in practice. Quality assurance of compounded formulations should be taken into consideration in hospital pharmacies.Peer reviewe

An optimization framework for the integration of water management and shale gas supply chain design

This study presents the mathematical formulation and implementation of a comprehensive optimization framework for the assessment of shale gas resources. The framework simultaneously integrates water management and the design and planning of the shale gas supply chain, from the shale formation to final product demand centers and from fresh water supply for hydraulic fracturing to water injection and/or disposal. The framework also addresses some issues regarding wastewater quality, i.e., total dissolved solids (TDS) concentration, as well as spatial and temporal variations in gas composition, features that typically arise in exploiting shale formations. In addition, the proposed framework also considers the integration of different modeling, simulation and optimization tools that are commonly used in the energy sector to evaluate the technical and economic viability of new energy sources. Finally, the capabilities of the proposed framework are illustrated through two case studies (A and B) involving 5 well-pads operating with constant and variable gas composition, respectively. The effects of the modeling of variable TDS concentration in the produced wastewater is also addressed in case study B

Solving Global Optimization Problems Using MANGO

Traditional approaches for solving global optimization problems generally rely on a single algorithm. The algorithm may be hybrid or applied in parallel. Contrary to traditional approaches, this paper proposes to form teams of algorithms to tackle global optimization problems. Each algorithm is embodied and ran by a software agent. Agents exist in a multiagent system and communicate over Our proposed MultiAgent ENvironment for Global Optimization (MANGO). Through Communication and cooperation, the agents complement each other in tasks that they cannot do on their own. This paper gives a formal description of MANGO and Outlines design principles for developing agents to execute Oil MANGO. Our case study shows the effectiveness of multiagent teams in solving global optimization problems