Types and frequency of errors in the preparation and administration of drugs / Tipos e frequência de erros no preparo e na administração de medicamentos endovenosos

ABSTRACT Objective: To identify compatibility, types and frequency of errors in preparation and administration of intravenous drugs. Methods: A cross-sectional and descriptive study performed at the emergency department of a university hospital in the city of São Paulo (SP). The sample consisted of 303 observations of the preparation and administration of intravenous drugs by nursing aides, nursing technicians and registered nurses, using a systematized script, similar to a checklist. The following variables were collected: errors related to dispensing, omission, schedule, unauthorized administration, dosage, formulation, incompatibility, preparation and administration. Results: In the preparation stage, the following errors were identified: no hand hygiene (70.29%), and no use of aseptic technique (80.85%). Upon administration, no hand hygiene (81.18%), and no use of aseptic technique (84.81%). In 31.35% of observations, there was more than one medication at the same time for the same patient, of which 17.89% were compatible, 56.84% were incompatible and 25.26% were not tested, according to the Micromedex database. Conclusion: In both preparation and administration stages, the most frequent errors were no hand hygiene and no use of aseptic technique, indicating the need to develop and implement education programs focused on patient safety.

RESUMO Objetivo: Identificar a compatibilidade, os tipos e a frequência de erros no preparo e na administração de medicamentos endovenosos. Métodos: Estudo transversal e descritivo, realizado em um serviço de emergência de um hospital universitário da cidade de São Paulo (SP). A amostra foi constituída por 303 observações do preparo e administração de medicamentos endovenosos por auxiliares, técnicos de enfermagem e enfermeiros, tendo como instrumento um roteiro sistematizado, do tipo checklist. As variáveis coletadas foram: erro de dispensação, omissão, horário, administração não autorizada, dose, apresentação, incompatibilidade, e erros de preparo e administração. Resultados: Na etapa de preparo, foram identificados os seguintes erros: não higienização das mãos (70,29%) e não usar técnica asséptica (80,85%). Na etapa de administração, 81,18% não higienizaram as mãos, e 84,81% não usaram a técnica asséptica. Em 31,35% das observações, existia mais de uma medicação no mesmo horário para o mesmo paciente; destas 17,89% eram compatíveis, 56,84% incompatíveis e 25,26% não foram testadas, conforme análise feita na base de dados Micromedex. Conclusão: Tanto na etapa do preparo quanto na de administração, os erros mais frequentes foram a não higienização das mãos e o não uso de técnica asséptica, apontando para a necessidade de desenvolvimento e implantação de programas de educação centrados na segurança do paciente.

Pharmaceutical development of tablets containing a spray-dried optimized extract from Lippia origanoides H. B. K.: influence of excipients and toxicological assessment

ABSTRACT Lippia origanoides is a honey shrub which has showed hypotensive potential assessed by in vivo studies. The aim of this work is the development of a pharmaceutical formulation composed by an optimized extract obtained from aerial parts of L. origanoides. The quantification of the naringenin marker in the dry extract and tablets developed was performed, as well as the assessment of the oral acute toxicity in rats. The hydroalcoholic extract of L. origanoides was spray-dried with the addition of colloidal silicon dioxide (Lo-HAE/CSD), and then applied in the preparation of eight different lots of tablets. The influence of the diluent (cellulose or babassu mesocarp), the presence of binder, and the percentage of lubricant, as well as organoleptic and physicochemical characteristics were screened. For the quantification of the marker content both in Lo-HAE/CSD and in the tablets, an analytical curve of the naringenin standard was fitted, and the samples were then analyzed in UFLC. The toxicological assessment was performed in female Wistar rats according to the Acute Toxic Class Method from OECD. The developed tablets produced meet acceptable macroscopic characteristics, and the presence of babassu as diluent provided improved physicochemical properties. The best content of Lo-HAE/CSD in the tablet (100.27%) was identified for the lot containing babassu, composed by 1.0% magnesium stearate, without PVP binder in its formulation. Moreover, Lo-HAE/CSD showed no signs of toxicity. Therefore, the babassu mesocarp powder is a promising pharmaceutical excipient for the development of herbal tablets containing the Lippia origanoides extract.

Spectrophotometric determination of rosuvastatin in pharmaceutical formulations using quinalizarin

ABSTRACT This work presents the development of a methodology based on the formation of a charge transfer complex between quinalizarin and rosuvastatin, allowing for the spectrophotometric determination of rosuvastatin at 579 nm. The factors involved in the sensitivity of the technique were studied (nature and proportion of the solvent, reaction time, pH of aqueous phase and quinalizarin concentration). The proposed spectrophotometric procedures were validated with respect to linearity, ranges, precision, accuracy, detection and quantification limits. Calibration curves of the formed color products showed good linear relationships over the concentration range of 6-15 mg L-1. The proposed method has been successfully applied, which can be confirmed by interference test (comparison between the standard curves and addition of analyte), method precision (RSD 2.3% to 6 mg L-1), and by accuracy (statistically equivalent results between the proposed method and a chromatographic method of reference).

Physical characterization of multiparticulate systems

ABSTRACT The search for new pharmaceutical dosage forms and different drug delivery systems already used in therapeutics is a global trend, serving as an opportunity to expand the portfolio for the pharmaceutical industry. In this context, multiparticulate systems, such as pellets, granules, and minitablets, represent an attractive alternative, given the range of possibilities they provide. Among the methods used in the production of these systems, we highlight the process of extrusion-spheronization for pellet manufacture, wet granulation and hot-melt extrusion for the obtention of granules, and direct compression for minitablets. Although highly versatile, depending on the technology chosen, many processes and formulation variables can influence the ensuing stages of manufacture, as well as the final product. Therefore, the characterization of these small units is of fundamental importance for achieving batch homogeneity and optimal product performance. Analyses, including particle size distribution, morphology, density, porosity, mechanical strength and disintegration, are example tests used in this characterization. The objective of this review was to address the most widely used tests for the physical evaluation of multiparticulate systems.

Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design

ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.

Development and evaluation of nefopam hydrochloride microcapsules

An attempt was performed to encapsulate Nefopam hydrochloride, a highly water soluble drug, by a modified emulsion solvent evaporation / extraction technique, using cellulose acetate butyrate [CAB] as a coating polymer. The influence of core/coat ratio [1:2, 1:1 and 2:1 ratio] on the yield, drug loading, size distribution as well as the release characteristics and surface topography of the prepared microcapsules was investigated. The obtained microcapsules exhibited higher encapsulation efficiency and a decreased release rate in simulated gastric fluid [S.G.F. pH 1.2] and simulated intestinal fluid [S.I.F. pH 7.4]. On the other hand, the entrapment efficiencies increased [from 104.66 to 141.26, core coat ratio 1:1] and the release rate decreased with increasing microcapsule size [from 250 to 512.5 micro m] and/or theoretical drug loading of microcapsules. Kinetic assessment of the release rate of microcapsules using different mathematical models has shown that the release followed Ritger-Peppas diffusion release kinetics

Aplicação do controle estatístico de processo na indústria farmacêutica / The application of statistical process control to the pharmaceutical industry

O controle estatístico de processo (CEP) é uma das mais poderosas metodologias desenvolvidas visando auxiliar no controle eficaz da qualidade. Através das cartas ou gráficos de controle, podem-se detectar desvios de parâmetros representativos do processo, reduzindo a quantidade de produtos fora de especificações e com isso os custos da produção. O controle estatístico de processo embora pouco utilizado na indústria farmacêutica, é uma ferramenta de grande utilidade, pois incorpora também o conceito de boas práticas de fabricação, além de fornecer informações imprescindíveis para a validação de processos, uma vez que permitem a investigação detalhada de todos os pontos críticos de controle, diagnosticando as possíveis não conformidades em todas as etapas do processo, além de sinalizar as possíveis fontes desses desvios de qualidade possibilitando correções e interações com o processo. Apesar de não existir muitas publicações do CEP na indústria farmacêutica, os exemplos de aplicações desta ferramenta provam sua grande importância para a compreensão dos processos que envolvem a obtenção de medicamentos