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.

Epidemiological methods for research with drug misusers: review of methods for studying prevalence and morbidity

Epidemiological studies of drug misusers have until recently relied on two main forms of sampling: probability and convenience. The former has been used when the aim was simply to estimate the prevalence of the condition and the latter when in depth studies of the characteristics, profiles and behaviour of drug users were required, but each method has its limitations. Probability samples become impracticable when the prevalence of the condition is very low, less than 0.5% for example, or when the condition being studied is a clandestine activity such as illicit drug use. When stratified random samples are used, it may be difficult to obtain a truly representative sample, depending on the quality of the information used to develop the stratification strategy. The main limitation of studies using convenience samples is that the results cannot be generalised to the whole population of drug users due to selection bias and a lack of information concerning the sampling frame. New methods have been developed which aim to overcome some of these difficulties, for example, social network analysis, snowball sampling, capture-recapture techniques, privileged access interviewer method and contact tracing. All these methods have been applied to the study of drug misuse. The various methods are described and examples of their use given, drawn from both the Brazilian and international drug misuse literature.

Clinical and laboratory parameters in dapsone acute intoxication

OBJECTIVE: To determine the severity of dapsone (DDS) acute intoxication – an uncommon medical event – using clinical and laboratory parameters. METHODS: Two hundred and seventy four patients with acute DDS intoxication, aged 1 month to 50 years old, were studied and classified into four age groups. Clinical evaluation was assessed through a protocol and correlated with laboratory parameters. Spectrophotometric methods were used to analyze methemoglobinemia (MHbp) and dapsonemia (DDSp). RESULTS: The most prevalent clinical sign of intoxication was cyanosis, seen in 65.7% of the patients and in 100% of children less than 5 years of age. According to laboratory criteria, MHbp-related severe clinical intoxication was seen in 56.2% and DDSp-related occurred in 58% of the patients. Regarding DDSp, intoxication was considered severe when 20 tablets (100 mg each) were ingested, a median of 29 mug/ml. Regarding MHbp, intoxication was severe when 7.5 tablets were ingested, a median of 38% of the total Hb. The correlation between MHbp and DDSp was statistically significant (n=144, r=0.32, p<0.05). Negative correlation was observed between MHbp and the time elapsed since DDS intake (n=124, r=-0.34, p<0.001). There was also a negative correlation between DDSp and the time elapsed since DDS intake (n=63, r=-0.35, p<0.0001). CONCLUSIONS: Longitudinal analysis showed a significant association between methemoglobinemia and the time elapsed after the intake (t), according to the equation: Dapsonemia = 12.9256 - 0.0682t + 0.234 methemoglobinemia

Drug abuse among workers in Brazilian regions

OBJECTIVE: Many business organizations in Brazil have adopted drug testing programs in the workplace since 1992. Rehabilitation, rather than layoff and disciplinary measures, has been offered as part of the Brazilian employee assistance programs. The purpose study is to profile drug abuse among company workers of different Brazilian geographical regions. METHODS: Urine samples of 12,700 workers from five geographical regions were tested for the most common illicit drugs of abuse in the country: marijuana, cocaine, and amphetamine. Enzyme multiplied immunoassay technique (EMIT) and gas chromatography coupled with mass spectrometry (GC/MS) were the techniques utilized for urine testing. The distribution of collected urine samples according to geographical regions was: 72.0% southeast, 13.8% northeast, 7.9% south, 5.7% central west and 0.6% north. RESULTS: Of all samples analyzed, 1.8% was found to be positive for drugs: 0.5% from the south region, 1.1% from northeast, 1.2% from central west, 1.3% from north, and 2.2% from southeast. Of these, 59.9% was marijuana, 17.7% cocaine, 14.6% amphetamine, and 7.7% associated drugs. CONCLUSIONS: The distribution of drugs found in the samples shows a regional variation. Marijuana, however, was found in all regions. Cocaine was seen only in central west and southeast regions. Amphetamine was found in northeast, central west, and southeast regions.

Prevalence of alcohol abuse and associated factors in a population-based study

OBJECTIVE: To estimate the prevalence of alcohol abuse/dependence and identify associated factors among demographic, family, socioeconomic and mental health variables. METHODS: A household survey was carried out in the urban area of Campinas, southeastern Brazil, in 2003. A total of 515 subjects, aged 14 years or more were randomly selected using a stratified cluster sample. The Self-Report Questionnaire and the Alcohol Use Disorder Identification Test were used in the interview. Prevalences were calculated, and univariate and multivariate logistic analyses performed by estimating odds ratios and 95% confidence intervals. RESULTS: The estimated prevalence of alcohol abuse/dependence was 13.1% (95% CI: 8.4;19.9) in men and 4.1% (95% CI: 1.9;8.6) in women. In the final multiple logistic regression model, alcohol abuse/dependence was significantly associated with age, income, schooling, religion and illicit drug use. The adjusted odds ratios were significantly higher in following variables: income between 2,501 and 10,000 dollars (OR=10.29); income above 10,000 dollars (OR=10.20); less than 12 years of schooling (OR=13.42); no religion (OR=9.16) or religion other than Evangelical (OR=4.77); and illicit drug use during lifetime (OR=4.47). Alcohol abuse and dependence patterns were different according to age group. CONCLUSIONS: There is a significantly high prevalence of alcohol abuse/dependence in this population. The knowledge of factors associated with alcohol abuse, and differences in consumption patterns should be taken into account in the development of harm reduction strategies.

Reliability of a questionnaire on substance use among adolescent students, Brazil

OBJECTIVE: To analyze reliability of a self-applied questionnaire on substance use and misuse among adolescent students. METHODS: Two cross-sectional studies were carried out for the instrument test-retest. The sample comprised male and female students aged 1119 years from public and private schools (elementary, middle, and high school students) in the city of Salvador, Northeastern Brazil, in 2006. A total of 591 questionnaires were applied in the test and 467 in the retest. Descriptive statistics, the Kappa index, Cronbach's alpha and intraclass correlation were estimated. RESULTS: The prevalence of substance use/misuse was similar in both test and retest. Sociodemographic variables showed a "moderate" to "almost perfect" agreement for the Kappa index, and a "satisfactory" (>0.75) consistency for Cronbach's alpha and intraclass correlation. The age which psychoactive substances (tobacco, alcohol, and cannabis) were first used and chronological age were similar in both studies. Test-retest reliability was found to be a good indicator of students' age of initiation and their patterns of substance use. CONCLUSIONS: The questionnaire reliability was found to be satisfactory in the population studied.

Prevalence of health promotion programs in primary health care units in Brazil

OBJECTIVE Assessment of prevalence of health promotion programs in primary health care units within Brazil’s health system. METHODS We conducted a cross-sectional descriptive study based on telephone interviews with managers of primary care units. Of a total 42,486 primary health care units listed in the Brazilian Unified Health System directory, 1,600 were randomly selected. Care units from all five Brazilian macroregions were selected proportionally to the number of units in each region. We examined whether any of the following five different types of health promotion programs was available: physical activity; smoking cessation; cessation of alcohol and illicit drug use; healthy eating; and healthy environment. Information was collected on the kinds of activities offered and the status of implementation of the Family Health Strategy at the units. RESULTS Most units (62.0%) reported having in place three health promotion programs or more and only 3.0% reported having none. Healthy environment (77.0%) and healthy eating (72.0%) programs were the most widely available; smoking and alcohol use cessation were reported in 54.0% and 42.0% of the units. Physical activity programs were offered in less than 40.0% of the units and their availability varied greatly nationwide, from 51.0% in the Southeast to as low as 21.0% in the North. The Family Health Strategy was implemented in most units (61.0%); however, they did not offer more health promotion programs than others did. CONCLUSIONS Our study showed that most primary care units have in place health promotion programs. Public policies are needed to strengthen primary care services and improve training of health providers to meet the goals of the agenda for health promotion in Brazil.

Prescription, dispensation and marketing patterns of methylphenidate

OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales – psychoactive and others – subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines.

Sexual transmission of hepatitis C

It is generally agreed that the hepatitis C virus (HCV) can be efficiently transmitted parenterally, although data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. Since data collection began in 1989, the first study dealt with the risk of sexual transmission among multiple sex partners. Other investigations followed, emphasizing that risk increases in specific groups such as patients co-infected with HIV and HBV, sex workers, homosexuals, illicit drug users and patients attended at sexually transmittable disease clinics. The question arises as to what might be the risk for monogamous heterosexuals in the general population, in which one of the partners has HCV? The literature provides overall rates that vary from zero to 27%; however, most studies affirm that the chances of sexual transmission are low or almost null, with rates for this mode fluctuating from zero to 3%. Intrafamilial transmission is strongly considered but inconclusive, since when mentioning transmission between sex partners within the same household, specific situations also should be considered, such as the sharing of personal hygiene items, like razorblades, toothbrushes, nail clippers and manicure pliers, which are important risk factors in HCV transmission. In this review, we discuss the hypotheses of sexual and/or intrafamilial transmission.