The Development of Magnetic Drug Delivery and Disposition

Available from: http://www.intechopen.com/books/the-delivery-of-nanoparticles/the-development-of-magnetic-drug-deliveryand-dispositionThe process of drug delivery and disposition in the modern scientific aspect is very complex. Advances in many fields are converging to make the commercialisation of advanced drug delivery concepts possible. It integrates many disciplines, including biotechnology, medicine and pharmacology. Innovative devices should protect labile active ingredients, precisely control drug release kinetics and minimise the release of the drug to non-target sites. Rapid advances in these areas led to the revolutionary change in discovery of new methods of drug delivery and disposition

Immobilization of Candida rugosa lipase onto magnetic beads for kinetic resolution of (R,S)-ibuprofen

Two commercially available lipases from Candida rugosa (CRL from Sigma-Aldrich Co. and OF from Meito Sangyo Co.) were immobilized onto glutaraldehyde-activated and EDC/sulfo-NHS-activated amineterminated magnetic beads (MB). In this study a procedure for immobilization of lipase OF using EDC sulfo-NHS onto the surface of magnetic particles was developed. The resulting “OF lipase enzymatic system” yielded good results of enantioselectivity (E=19, eep=83%) and conversion (c=42%) of the kinetic resolution of (R,S)-ibuprofen. Additionally, this procedure provides easy recovery and effective reuse of lipase OF, maintaining the enantioselectivity of the reaction on the same high level after five cycles. It was also demonstrated that the cross-linking reaction of lipases (CRL and OF) via glutaraldehyde onto magnetic support did not result in acceptable levels of conversion and enantioselectivity of the esterification reaction. Based on the results it should be noted that the immobilization technique we studied using EDC and sulfo-NHS onto MB could be potentially important for industrial application of kinetic resolution of non-steroidal anti-inflammatory drugs

Application of Lipases from Candida rugosa in the Enantioselective Esterification of (R, S)-Ibuprofen

Three commercially available lipases from Candida rugosa (OF and MY from Meito Sangyo Co., and CRL from Sigma-Aldrich Co.) were used for the enantioselective esterification reaction of (R,S)-ibuprofen with 1-propanol and 2-propanol in saturated cyclohexane as reaction medium. All tested lipases preferentially catalysed the esterification of the S-enantiomer of ibuprofen. However, each one of the analysed lipases demonstrated differences in the catalytic activity. Lipase OF showed the highest conversion degree, and the best enantioselectivity was observed for MY and CRL lipases. The influence of temperature, reaction time and addition of N,N’- dicyclohexylcarbodiimide (DCC) on the enantioselectivity and on the conversion degree in the enzymatic esterification was studied and the optimal condition for nantioselective esterification was evaluated. Moreover, the application of new commercial cellulose-based tris(3,5-dimethylphenylcarbamate) HPLC chiral column was demonstrated for effective separation, qualification and quantification of both substrates and products within one chromatographic analysis

Ionic Liquids: A New Strategy in Pharmaceutical Synthesis

The industrial synthesis of pharmaceutical compounds often involves the use of organic solvents. Unfortunately, these reaction media are responsible for organic contaminations in the final product. In recent years, ionic liquids (ILs) have become the “green alternatives” of volatile organic solvents. Thus, the application of ILs instead of conventional reagents offer a new opportunity to solve problems of environmentally harmful solvents. This mini-review discusses a new application of ILs in laboratory-scale pharmaceutical synthesis

Application of green chemistry in decreasing adverse effect of (R,S)-ibuprofen

Lipases from Candida rugosa (OF and MY) were tested for their application in the enzymatic kinetic resolution of (R,S)-ibuprofen by enantioselective esterification. In this study, screening of enzymes was performed, and lipase MY was selected as an optimal catalyst, which allows to obtain products with high enantiopurity. Additionally, the influence of reaction time on the enantiomeric ratio and conversion was tested. High values of enantiomeric ratio (E in the range of 40.1–71.3) of the esterification of (R,S)- -ibuprofen were obtained using lipase MY, which has a great significance in the field of pharmaceutical synthesis of drugs. The chiral compounds (substrates and products) were analysed with the use of chiral stationary phases. As a result of the optimization, the reaction performed with the application of lipase MY allowed to achieve less toxic for human health (S)-enantiomer of ibuprofen with the high enantiomeric excess of product eep = 95%. Conversion of the reaction was c = 30.6% and enantioselectivity E = 58.9 after 126 h of incubation

Statystyczne i chemometryczne metody analizy danych w chemii medycznej i biologii

Materiały do wykładów prowadzonych w ramach projektu pn. „Wzmocnienie potencjału dydaktycznego UMK w Toruniu w dziedzinach matematyczno-przyrodniczych” realizowany w ramach Poddziałania 4.1.1 Programu Operacyjnego Kapitał LudzkiPrzedmiotem wykładu są wybrane statystyczne i chemometryczne metody, przydatne w planowaniu eksperymentu i analizie danych uzyskanych w takich dziedzinach badawczych jak biologia czy chemia medyczna. Program wykładu obejmuje: elementy chemii medycznej, szczególnie molekularne podstawy działania substancji leczniczych, projektowanie nowych substancji o potencjalnym działaniu farmakologicznym i analizę związku między strukturą cząsteczki a jej właściwościami biologicznymi; metody statystyczne (ANOVA, testy t, parametryczne i nieparametryczne) i chemometryczne techniki klasyfikacyjne (analiza skupień, analiza czynnikowa, analiza głównych składowych, analiza dyskryminacyjna) oraz kalibracyjne (regresja wieloraka, regresja metodą najmniejszych cząstkowych kwadratów); założenia metod, przygotowanie danych i ich kontrolę, wnioskowanie i interpretację; metody wizualizacji danych surowych i wyników analizy; przykłady ilustrujące omawiane zagadnienia i przykłady kompleksowej analizy danych

Affinity Chromatography Method for Determination of Binding of Drugs to Melanin and Evaluation of Side Effect Potential of Antipsychotic Agents

The extrapyramidal side effect parameters of typical and atypical antypsychotics were correlated with affinity chromatographic data determined on the melanin-based column. The chromatographic study was performed according to the hypothesis that extrapyramidal symptoms (EPS) as side effects of the use of antipsychotic drugs at clinically effective doses are correlated to the affinity of these drugs to neuromelanin. For that aim the polymerization product of L-DOPA (melanin) was immobilized onto aminopropyl silica and the binding efficiency of melanin towards antipsychotics has been determined. The results indicate that melanin based-column can be used to evaluate the risk of EPS of drug candidates to antipsychotic drug therapy

Lipase B from Candida antarctica — the wide applicable biocatalyst in obtaining pharmaceutical compounds

Lipases are commonly applied in the pharmaceutical and chemical industry, especially in immobilizedform. The use of immobilized lipases facilitates the design of reactors and control of reactions, for example,fast stopping the reaction. The immobilization procedure should increase the stability of the lipaseand its activity, as well as be simple and efficient. Lipase B from Candida antarctica (CAL-B) is an enzymefrom the lipase group, isolated from the Candida antarctica species. CAL-B has the highest activity innon-polar organic solvents, such as hexane and toluene, and the lowest in polar solvents, e.g. acetonitrile.Due to its hydrolytic properties, this enzyme degrades triglycerides of fatty acids to free fatty acids (FFA)and glycerol. Described lipase is often immobilized, in the aim to increase enantioselective and lipolyticactivity. The kinetic and dynamic resolution with the application of lipase is one of the ways in obtainingan enantiopure form of the drugs, which usually are more effective and safer for the patient. The CAL-Bcould be also applied in the kinetic resolution of compounds being building blocks, derivates of drugs orconjugated forms. Furthermore, the CAL-B is used in the reactions in receiving of organic compounds,which are the natural origin, especially vegetable. Based on the presented data, it can be concluded, thatCAL-B is an enzyme with a wide application in the biosynthesis of compounds with therapeutic activity

Influence of the Anionic Part of 1-Alkyl-3-Methylimidazolium-Based Ionic Liquids on the Chromatographic Behavior of Perazine in RP-HPTLC

1-Alkyl-3-methylimidazolium-based ionic liquids (tetrafluoroborate, L-(ţ)-lactate and ethyl sulfate) were used as mobile phase additives to assess the effect of its anionic part on the retention mechanism of perazine in pharmaceutical formulation in reversed-phase highperformance thin-layer chromatography (RP-HPTLC) method. In all cases, significant changes and improvements in the retention factor were observed when ionic liquids were added to the mobile phase. We found that the chromatographic behavior of the basic analyte depends on the utilized ionic liquid as well as its various anions. Enhancement of separation confirms silanol suppressing potency of employed ionic liquids and their positive impact on chromatographic separation of basic drugs. Among selected ionic liquids, the optimum distribution parameters such as shape and quality of spots, high precision, and accuracy in qualitative and quantitative determination characterize the system with [EMIm][BF4] as mobile phase modifier. Our proposed HPTLC method for determination of perazine in oral tablets was also subjected to subsequent validation procedure in accordance with ICH guidelines and proved to be suitable, inexpensive, and convenient method in a pharmaceutical analysi

1-ALKYL-3-METHYLIMIDAZOLIUM TETRAFLUOROBORATE AS AN ALTERNATIVE MOBILE PHASE ADDITIVES FOR DETERMINATION OF HALOPERIDOL IN PHARMACEUTICAL FORMULATION BY HPTLC UV DENSITOMETRIC METHOD

An alternative thin-layer chromatography (TLC) method for the determination of haloperidol in pharmaceutical formulation against the method proposed by European Pharmacopeia (7.0) has been compared and described. The proposed method uses a mobile phase composed of acetonitrile/ water, 60:40, with the addition of 1.5% (v/v) 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid. The ionic liquid modifiers of a mobile phase have been shown to be suitable suppressor of silanol ionization in the TLC of basic drugs. Besides the silanol-suppressing potency of the 1-ethyl-3-methylimidazolium tetrafluoroborate, the lack of interaction and interference with UV densitometric detection was observed. These properties open a new possibilities in the application of alky-imidazolium-based ionic liquids in chromatographic techniques