Development of new dissolution test and HPLC-RP method for anti-parasitic ornidazole coated tablets

This work aimed the development and validation of a new dissolution test for ornidazole coated tablets. The dissolution conditions were determined after testing Sink conditions, dissolution medium, apparatus, stirring speed, 24 h stability and medium filtration influence. The best conditions were paddle at a stirring speed of 75 rpm and 900 mL of 0.1 M HCl. A new HPLC quantification method was developed and validated. The dissolution test and quantification method showed to be adequate for their purposes and could be applied for quality control of ornidazole coated tablets, since there is no official monograph.

UV derivative spectrophotometric method for determination of estradiol valerate in tablets

A derivative UV spectrophotometric method for determination of estradiol valerate in tablets was validated. The parameters specificity, linearity, precision, accuracy, limit of detection and limit of quantitation were studied according to validation guidelines. The first-order derivative spectra were obtained at N = 5, Δλ = 4.0 nm, and determinations were made at 270 nm. The method showed specificity and linearity in the concentration range of 0.20 to 0.40 mg mL-1. The intra and interday precision data demonstrated the method has good reproducibility. Accuracy was also evaluated and results were satisfactory. The proposed method was successfully applied to a pharmaceutical formulation.

Development and validation of an UV spectrophotometric method for the determination of aliskiren in tablets

For determination of aliskiren in commercial samples, an analytical UV spectrophotometric method was developed and validate according to ICH guideline. The method was linear in the range between 40 and 100 μg mL-1 (r² = 0.9997, n = 7) and exhibited suitable specificity, accuracy, precision, and robustness. It is simple, it has low cost, and it has low use polluting reagents. Therefore, the proposed method was successfully applied for the assay and dissolution studies of aliskiren in tablet dosage forms, and the results were compared to a validated RP-LC method, showing non-significant difference (P > 0.05).

Chemical stability of enalapril maleate drug substance and tablets by a stability-indicating liquid chromatographic method

The chemical stability of enalapril drug substance and tablets was studied by a stability-indicating liquid chromatographic method. Stress testing was performed on drug substance under various conditions. Accelerated stability testing was carried out for different formulations of enalapril tablets. Chromatographic separation was achieved on a RP-18 column, using a mobile phase of methanol phosphate buffer at 1.0 mL min"1 and UV detection. Degradation of the drug substance was greater under hydrolytic conditions. After 180 days of accelerated stability testing most enalapril tablets showed more than 10% of degradation. Enalapril drug substance and tablets showed instability under stress and accelerated testing respectively, with possible implications on the therapeutic activity.

Development and validation of a stability-indicating HPLC method for the determination of buclizine hydrochloride in tablets and oral suspension and its application to dissolution studies

A method using liquid chromatography has been developed and validated for determination of buclizine in pharmaceutical formulations and in release studies. Isocratic chromatography was performed on a C18 column with methanol:water (80:20 v/v, pH 2.6) as mobile phase, at a flow rate of 1.0 mL/min, and UV detection at 230 nm. The method was linear, accurate, precise, sensible and robust. The dissolution test was optimized and validated in terms of dissolution medium, apparatus agitation and rotation speed. The presented analytical and dissolution procedures can be conveniently adopted in the quality and stability control of buclizine in tablets and oral suspension.

Simvastatin assay and dissolution studies by feasible RP-HPLC in tablets

Commonly used HPLC acetonitrile solvent has been through a worldwide shortage with a cost increase in 2008 and 2009. In order to get around this situation, a method by RP-HPLC employing methanol and aqueous acid mobile phase was developed and validated to evaluate simvastatin. The quality control assay and dissolution studies of this lipid-lowering drug were performed in diluents methanol and 0.01 M phosphate buffer with 0.5% SDS, pH 7, respectively. Dissolution test aliquots did not go through sample treatment, as described in USP SIM tablets monograph by ultraviolet spectrophotometry. The proposed method is fast, simple, feasible and robust.

Development and validation of a dissolution test for primaquine/polyethylene oxide matrix tablets

A simple, precise, specific, repeatable and discriminating dissolution test for primaquine (PQ) matrix tablets was developed and validated according to ICH and FDA guidelines. Two UV assaying methods were validated for determination of PQ released in 0.1 M hydrochloric acid and water media. Both methods were linear (R²>0.999), precise (R.S.D.<1.87%) and accurate (97.65-99.97%). Dissolution efficiency (69-88%) and equivalence of formulations (f2) was assessed in different media and apparatuses (basket/100 rpm and paddle/50 rpm) tested. Discriminating condition was 900 mL aqueous medium, basket at 100 rpm and sampling times at 1, 4 and 8 h. Repeatability (R.S.D.<2.71%) and intermediate precision (R.S.D.<2.06%) of dissolution method were satisfactory.

Simultaneous and accurate determination of water- and fat-soluble vitamins in multivitamin tablets by using an RP-HPLC method

In the present study, a reversed-phase high-performance liquid chromatographic (RP-HPLC) procedure was developed and validated for the simultaneous determination of seven water-soluble vitamins (thiamine, riboflavin, niacin, cyanocobalamin, ascorbic acid, folic acid, and p-aminobenzoic acid) and four fat-soluble vitamins (retinol acetate, cholecalciferol, α-tocopherol, and phytonadione) in multivitamin tablets. The linearity of the method was excellent (R² > 0.999) over the concentration range of 10 - 500 ng mL-1. The statistical evaluation of the method was carried out by performing the intra- and inter-day precision. The accuracy of the method was tested by measuring the average recovery; values ranged between 87.4% and 98.5% and were acceptable quantitative results that corresponded with the label claims.

Interaction study of moxifloxacin with Cu(II) ion using square-wave voltammetry and its application in the determination in tablets

This work presents an electroanalytical method for the determination of moxifloxacin (MOXI) in tablets by its interaction with Cu(II) ion and subsequent electrochemical reduction at hanging mercury drop electrode (HMDE). A well-defined reduction peak at -0.21 V vs. Ag/AgCl in Phosphate buffer 0.04 mol L-1 pH 8.0 was observed for the complex reduction MOXI-Cu(II), using square-wave voltammetry (SWV). Using a 10 s of accumulation time at -0.40 V was found a limit detection of 3.60x10-8 mol l-1. The obtained results have shown good agreement with those obtained by spectrophotometric method.

Technological development of 40mg furosemide tablets: equivalence and bioavaibility study in dogs

Furosemide (40mg) was administered to 20 street dogs, 10 males and 10 females, in two different pharmaceutical forms: (1) compressed furosemide 40mg formulated at the Federal University of Pernambuco (UFPE-tablet), and (2) a commercial formulation with equal bioequivalence produced by the Laboratory for Pharmaceutical Technology of Pernambuco State (LAFEPE), the LAFEPE-furosemide. The study aimed to evaluate the kinetics of dissolution of the UFPE-tablet in order to analyze the behavior of bioavailability of the best formulation for veterinary use. The plasmatic concentrations of furosemide for the determination of parameters of pharmacological kinetics were analyzed by high-performance liquid chromatographic method (HPLC). The in vitro study accomplished through physiochemical analyses demonstrated that the formulas of the furosemide tablets attained the pharmaceutical requirements in agreement with USP 23 and the Brazilian Pharmacopoeia. The evaluation accomplished in dogs with UFPE-tablets given in only dose demonstrated uniformity in blood levels indicating stability in maintenance of the pharmaceutical formulation and efficiency in absorption of the active compound. These values are not significantly different in relation to the 5% confidence limit. Regarding maximum concentration (Tmax) time and global bioavaibility assessed by AUC means, there were no considerable differences as well. UFPE-furosemide displayed 743.492µg/mL.h as AUC average value whereas LAFEPE-furosemide had an average of 537.284µg/mL.h.

Detection of Illicit Drugs and Drug Precursors with Cantilever-Enhanced Photoacoustic Spectroscopy

In this study, cantilever-enhanced photoacoustic spectroscopy (CEPAS) was applied in different drug detection schemes. The study was divided into two different applications: trace detection of vaporized drugs and drug precursors in the gas-phase, and detection of cocaine abuse in hair. The main focus, however, was the study of hair samples. In the gas-phase, methyl benzoate, a hydrolysis product of cocaine hydrochloride, and benzyl methyl ketone (BMK), a precursor of amphetamine and methamphetamine were investigated. In the solid-phase, hair samples from cocaine overdose patients were measured and compared to a drug-free reference group. As hair consists mostly of long fibrous proteins generally called keratin, proteins from fingernails and saliva were also studied for comparison. Different measurement setups were applied in this study. Gas measurements were carried out using quantum cascade lasers (QLC) as a source in the photoacoustic detection. Also, an external cavity (EC) design was used for a broader tuning range. Detection limits of 3.4 particles per billion (ppb) for methyl benzoate and 26 ppb for BMK in 0.9 s were achieved with the EC-QCL PAS setup. The achieved detection limits are sufficient for realistic drug detection applications. The measurements from drug overdose patients were carried out using Fourier transform infrared (FTIR) PAS. The drug-containing hair samples and drug-free samples were both measured with the FTIR-PAS setup, and the measured spectra were analyzed statistically with principal component analysis (PCA). The two groups were separated by their spectra with PCA and proper spectral pre-processing. To improve the method, ECQCL measurements of the hair samples, and studies using photoacoustic microsampling techniques, were performed. High quality, high-resolution spectra with a broad tuning range were recorded from a single hair fiber. This broad tuning range of an EC-QCL has not previously been used in the photoacoustic spectroscopy of solids. However, no drug detection studies were performed with the EC-QCL solid-phase setup.

The Political Economy of St. Catharines' Illicit Taxi Trade

The global restructuring of production has led to increasingly precarious working conditions around the world. Post-industrial work is characterized by poor working conditions, low wages, a lack of social protection and political representation and little job security. Unregulated forms of work that are defined as “irregular” or “illegal”, or in some cases “criminal,” are connected to sweeping transformations within the broader regulated (formal) economy. The connection between the formal and informal sectors can more accurately be described as co-optation and, as a subordinate integration of the informal to the formal. The city of St. Catharines within Niagara, along with much of Ontario’s industrial heartland, has been hard hit by deindustrialization. The rise of this illegal service is thus viewed against the backdrop of heavy economic restructuring, as opportunities for work in the manufacturing sector have become sparse. In addition, this research also explores the paradoxical co-optation of the growing illicit taxi economy and consequences for racialized and foreign credentialed labour in the taxi industry. The overall objective of this research is to explore the illicit cab industry as not only inseparable from the formal economy, but dialectically, how it is as an integrated and productive element of the public and private transportation industry. Furthermore the research examines what this co-optation means in the context of a labour market that is split by race.

Formulation development and characterization of liquisolid tablets containing clozapine

L’objectif de ce projet était de développer une formulation liquisolide (LS) de clozapine ayant des propriétés de dissolution améliorées et évaluer sa stabilité et ainsi que sa robustesse à la modification d’excipients. Le propylène glycol (PG), la cellulose microcrystalline (MCC) et le glycolate d’amidon sodique (SSG) ont été utilisés respectivement en tant que véhicule liquide non volatile, agent de masse et agent désintégrant pour la préparation de comprimés LS. Le dioxyde de silicium colloïdal (CSD), le silicate de calcium (CS) et l'aluminométasilicate de magnésium (MAMS) ont été choisis comme agents d’enrobage sec. La caractérisation complète des mélanges et des comprimés a été effectuée. Le taux de libération des comprimés LS était statistiquement supérieur à celui des comprimés réguliers. La surface spécifique des matériaux d’enrobage avait un effet sur les propriétés d’écoulement des mélanges et la taille des particules des matériaux d’enrobage a eu un effet sur la vitesse de dissolution. Le ratio support/enrobage du mélange de poudres (valeur de R) était un paramètre important pour les systèmes LS et devait être plus grand que 20 afin d’obtenir une meilleure libération du médicament. La formulation choisie a démontré une stabilité pour une période d’au moins 12 mois. La technique LS s’est avéré une approche efficace pour le développement de comprimés de clozapine ayant des propriétés de dissolution améliorées. Les comprimés oro-dispersibles (ODT) sont une formulation innovante qui permettent de surmonter les problèmes de déglutition et de fournir un début d'action plus rapide. Dans l’optique d’améliorer les propriétés de dissolution, un essai a été effectué pour étudier la technique LS dans la formulation des ODT de clozapine. Le PG, la MCC, le CSD et la crospovidone (CP) ont été utilisés respectivement en tant que véhicule liquide non volatile, agent de masse, agent d’enrobage sec et agent superdésintégrant pour la préparation de comprimés oro-dispersibles liquisolides (OD-LST). Le mannitol a été choisi comme agent de masse et agent édulcorant. La saccharine de sodium a été utilisée comme agent édulcorant. La caractérisation complète des comprimés a été effectuée. Le taux de libération des OD-LSTs était statisquement supérieur comparativement aux comprimés ODTs. La formulation choisie a démontré une stabilité pour une période d’au moins 6 mois. Il a été conclu que des ODT de clozapine peuvent être préparés avec succès en utilisant la technologie LS dans le but d’améliorer la désintégration et le taux de dissolution de la clozapine dans la cavité orale.

Comorbid Depression Among Untreated Illicit Opiate Users : Results From a Multisite Canadian Study

This study aimed to describe patterns of major depression (MDD) in a cohort of untreated illicit opiate users recruited from 5 Canadian urban centres, identify sociodemographic characteristics of opiate users that predict MDD, and determine whether opiate users suffering from depression exhibit different drug use patterns than do participants without depression. Baseline data were collected from 679 untreated opiate users in Vancouver, Edmonton, Toronto, Montreal, and Quebec City. Using the Composite International Diagnostic Interview Short Form for Major Depression, we assessed sociodemographics, drug use, health status, health service use, and depression. We examined depression rates across study sites; logistic regression analyses predicted MDD from demographic information and city. Chi-square analyses were used to compare injection drug use and cocaine or crack use among participants with and without depression. Almost one-half (49.3%) of the sample met the cut-off score for MDD. Being female, white, and living outside Vancouver independently predicted MDD. Opiate users suffering from depression were more likely than users without depression to share injection equipment and paraphernalia and were also more likely to use cocaine (Ps < 0.05). Comorbid depression is common among untreated opiate users across Canada; targeted interventions are needed for this population.

Pilot study of the short-term physico-chemical stability of atenolol tablets stored in a multi-compartment compliance aid

Study objectives: There is a possibility that lower air, moisture and light protection could impact on physico-chemical stability of medicines inside multi-compartment compliance aids (MCCAs), although this has not yet been proved. The objectives of the study were to examine the physico-chemical stability of atenolol tablets stored in a compliance aid at room temperature, and at elevated temperature and humidity to simulate practice conditions. Methods: Atenolol 100 mg tablets in 28-chamber, plastic compliance aids with transparent lids were stored for four weeks at room temperature and at 40°C with 75% relative humidity. Tablets were also stored at room temperature in original packaging and Petri dishes. Physical tests were conducted to standards as laid down in the British Pharmacopoeia 2005, and dissolution to those of the United States Pharmacopoeia volume 24. Chemical stability was assessed by a validated high-performance liquid chromatography (HPLC) method. Results: Tablets at room temperature in original packaging, in compliance aids and Petri dishes remained the same in appearance and passed physico-chemical tests. Tablets exposed to 40°C with 75% relative humidity in compliance aids passed tests for uniformity of weight, friability and chemical stability but became pale and moist, softer (82 newtons ± 4; p< 0.0001) than tablets in the original packaging (118 newtons ± 6), more friable (0.14% loss of mass) compared with other tablets (0.005%), and failed the tests for disintegration (>15 minutes) and dissolution (only 15% atenolol released at 30 minutes). Conclusion: Although chemical stability was unaffected, storage in compliance aids at 40°C with 75% relative humidity softened atenolol tablets, prolonged disintegration time and hindered dissolution which could significantly reduce bioavailability. This formulation could be suitable for storage in compliance aids at 25°C, but not in hotter, humid weather.