Nanoemulsions containing amphotericin b and paromomycin for the treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a vector-borne disease characterized by skin lesions that can evolve into high-magnitude ulcerated lesions. Thus, this study aimed to develop an innovative nanoemulsion (NE) with clove oil, Poloxamer® 407, and multiple drugs, such as amphotericin B (AmB) and paromomycin (PM), for use in the topical treatment of CL. METHODS: Droplet size, morphology, drug content, stability, in vitro release profile, in vitro cytotoxicity on RAW 264.7 macrophages, and antileishmanial activity using axenic amastigotes of Leishmania amazonensis were assessed for NEs. RESULTS: After optimizing the formulation parameters, such as the concentration of clove oil and drugs, using an experimental design, it was possible to obtain a NE with an average droplet size of 40 nm and a polydispersion index of 0.3, and these parameters were maintained throughout the 365 days. Furthermore, the NE showed stability of AmB and PM content for 180 days under refrigeration (4 °C), presented a pH compatible with the skin, and released modified AmB and PM. NE showed the same toxicity as free AmB and higher toxicity than free PM against RAW 264.7 macrophages. The same activity as free AmB, and higher activity than free PM against amastigotes L. amazonensis. CONCLUSION: It is possible to develop a NE for the treatment of CL; however, complementary studies regarding the antileishmanial activity of NE should be carried out.

Bacaba, Pracaxi and Uxi Oils for Therapeutic Purposes: A Scoping Review.

Fruits such as bacaba (Oenocarpus bacaba Mart), pracaxi (Pentaclethra macroloba Kuntze) and uxi (Endopleura uchi (Huber) Cuatrec), from the Amazon rainforest, are potentially interesting for studies of natural products. The current article aims at mapping and characterizing studies on the bacaba, pracaxi and uxi species. This review reports the main bioactive compounds identified in these species and discusses their therapeutic potential. Searches were performed in MEDLINE (Via Pubmed) and Web of Science. Thirty-one studies that described or evaluated the development of formulations aimed at the therapeutic use of the species were included. The findings suggest that species have the potential for the development of pharmaceutical formulations due to their therapeutic properties. However, further studies are required to assess safety and efficacy of these products. Therefore, it is suggested that new research studies propose strategies so that technological development is based on awareness and preservation of the biome.

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.

Compounded medications for cardiovascular use in neonatology: an integrative review / Medicamentos manipulados de uso cardiovascular em neonatologia: uma revisão integrativa

ABSTRACT Objective: To analyze the profile of the compounded cardiovascular medicines prescribed in neonatology in Brazil. Data source: An integrative bibliographic review was carried out, including studies published in the last 20 years. The used descriptors were: Intensive Care Neonatal, Off-Label Use, Pharmaceutical Preparations, in the databases Virtual Health Library (VHL), PubMed, and Scientific Electronic Library Online (SciELO). Review articles and guidelines were excluded. The quality of the evidence was analyzed, and 10 articles were selected to integrate the study. Data synthesis: The profile of routine prescrption in the neonatal unit was evaluated. The main cardiovascular medications prescribed as compounding formulation were: Spironolactone, Captopril, Furosemide, Hydrochlorothiazide, Propranolol, Amiodarone, Nifedipine, Carvedilol, Digoxin, Enalapril, Epinephrine, and Hydralazine. The drugs were obtained from adaptations of dosage forms, through the transformation of capsules or tablets into liquid formulations, as a solution, suspension, or syrup, as well as in the form of solutions prepared from active pharmaceutical ingredients. The compounding of medications made drug therapy possible in neonatology, considering that such medications do not have registration of the oral liquid dosage form in the country, despite being part of the List of Essential Medicines for Children of the Word Health Organization. Conclusions: It was possible to analyze the profile of compounded cardiovascular medicines prescribed in neonatology in Brazil. The results showed the need for the development of medications suitable for the neonatal population, and the standardization of operational procedures for preparing extemporaneous formulations in neonatology to increase drug safety.

RESUMO Objetivo: Analisar o perfil dos medicamentos cardiovasculares manipulados prescritos em neonatologia no Brasil. Fontes de dados: Foi realizada uma revisão bibliográfica integrativa, incluindo estudos publicados nos últimos 20 anos. As palavras-chave utilizadas foram: intensive care neonatal, off-label use, pharmaceutical preparations, nos bancos de dados da Biblioteca Virtual em Saúde (BVS), PubMed e Biblioteca Eletrônica Científica Online (SciELO). Os artigos de revisão e diretrizes foram excluídos. A qualidade da evidência foi analisada, e foram selecionados 10 artigos para integrar o estudo. Síntese dos dados: Todos os estudos possibilitaram a avaliação do perfil de prescrição na rotina da unidade. Os principais fármacos cardiovasculares, prescritos em formulação extemporânea, foram espironolactona, captopril, furosemida, hidroclorotiazida, propranolol, amiodarona, nifedipina, carvedilol, digoxina, enalapril, epinefrina e hidralazina. Os medicamentos foram obtidos mediante adaptações de formas farmacêuticas, por meio da transformação de cápsulas ou comprimidos em formulações líquidas, como solução, suspensão ou xarope, assim como também na forma de soluções preparadas com base nos insumos farmacêuticos ativos. A manipulação de medicamentos tornou possível o tratamento medicamentoso em neonatologia, uma vez que tais medicamentos não possuem registro da forma farmacêutica líquida oral no país, apesar de integrarem a lista de medicamentos essenciais em pediatria da Organização Mundial da Saúde. Conclusões: Foi possível analisar o perfil dos medicamentos cardiovasculares manipulados prescritos na neonatologia no Brasil. Os resultados evidenciaram a necessidade do desenvolvimento de medicamentos adequados à população neonatal e à padronização dos procedimentos operacionais do preparo de formulações extemporâneas na neonatologia, para aumentar a segurança dos medicamentos.

Compounded medications for cardiovascular use in neonatology: an integrative review.

OBJECTIVE: To analyze the profile of the compounded cardiovascular medicines prescribed in neonatology in Brazil. DATA SOURCE: An integrative bibliographic review was carried out, including studies published in the last 20 years. The used descriptors were: Intensive Care Neonatal, Off-Label Use, Pharmaceutical Preparations, in the databases Virtual Health Library (VHL), PubMed, and Scientific Electronic Library Online (SciELO). Review articles and guidelines were excluded. The quality of the evidence was analyzed, and 10 articles were selected to integrate the study. DATA SYNTHESIS: The profile of routine prescrption in the neonatal unit was evaluated. The main cardiovascular medications prescribed as compounding formulation were: Spironolactone, Captopril, Furosemide, Hydrochlorothiazide, Propranolol, Amiodarone, Nifedipine, Carvedilol, Digoxin, Enalapril, Epinephrine, and Hydralazine. The drugs were obtained from adaptations of dosage forms, through the transformation of capsules or tablets into liquid formulations, as a solution, suspension, or syrup, as well as in the form of solutions prepared from active pharmaceutical ingredients. The compounding of medications made drug therapy possible in neonatology, considering that such medications do not have registration of the oral liquid dosage form in the country, despite being part of the List of Essential Medicines for Children of the Word Health Organization. CONCLUSIONS: It was possible to analyze the profile of compounded cardiovascular medicines prescribed in neonatology in Brazil. The results showed the need for the development of medications suitable for the neonatal population, and the standardization of operational procedures for preparing extemporaneous formulations in neonatology to increase drug safety.

Farmacovigilância de medicamentos manipulados - Parte 1: perfil das notificações no Brasil / Pharmacovigilance of compounded drugs - Part 1: profile of Brazilian notifications

Introdução: Medicamentos manipulados são preparações farmacêuticas extemporâneas, em sua maioria utilizadas para viabilizar a farmacoterapia de populações especiais por meio de formulações personalizadas. Desta forma, não são submetidos a testes clínicos anteriores a sua utilização, sendo as ações de farmacovigilância fundamentais para a garantia de sua segurança. Objetivo: Descrever o perfil dos medicamentos manipulados registrados nas notificações de queixas técnicas reportadas ao Sistema Nacional de Notificação em Vigilância Sanitária (Notivisa). Método: Estudo exploratório descritivo, retrospectivo ao período de 2006-2016 das notificações de medicamentos manipulados reportadas ao Notivisa. Resultados: Foram analisadas 303 notificações de queixas técnicas referentes a 26 medicamentos oficinais, 268 magistrais e nove não classificadas. Foram identificados 107 diferentes ativos. Os de ação no aparelho digestivo e metabolismo foram os mais frequentes (42,00%), seguidos daqueles com ação no sangue e órgãos hematopoiéticos (10,00%), dermatológicos (10,00%) e aparelho cardiovascular (9,70%). Os principais desvios de qualidade notificados foram relacionados às formas farmacêuticas líquidas, sendo a presença de corpo estranho, partículas ou precipitados, a mais frequente (22,40%), seguida de alterações na embalagem e rotulagem (18,60%). Conclusões: Foi possível descrever os principais medicamentos manipulados notificados ao Notivisa, suas características e substâncias ativas veiculadas nas formulações, o que pode contribuir para as ações de vigilância sanitária no âmbito magistral, tão incipiente ainda no Brasil.

Introduction: Compounded drugs are extemporaneous pharmaceutical preparations, mostly used to enable the pharmacotherapy of special populations through personalized formulations. In this way, they are not subjected to clinical tests prior to their use, and pharmacovigilance actions are fundamental to guarantee their safety. Objective: to describe the profile of compounded drugs registered in the notifications of technical complaints reported to the National Health Surveillance Notification System (NOTIVISA). Method: Descriptive exploratory study, retrospective to the period 2006-2016, of the notifications of compounded drugs reported to Notivisa. Results: 303 notifications of technical complaints regarding 26 officinal, 268 magistral and 09 unclassified medicines were analyzed. 107 different assets were identified. Those with action on the Digestive System and Metabolism were the most frequent (42.00%), followed by those with action on the Blood and Hematopoietic Organs (10.00%), Dermatological (10.00%) and Cardiovascular System (9.70%). The main quality deviations reported were related to liquid dosage forms, with the presence of foreign bodies, particles or precipitates being the most frequent (22.40%), followed by changes in packaging and labeling (18.60%). Conclusions: It was possible to describe the main compounded drugs notified to Notivisa, their characteristics and active substances conveyed in the formulations, which can contribute to the actions of Health Surveillance in the masterful scope, which is still incipient in Brazil.

Farmacovigilância de medicamentos manipulados - Parte 2: notificações de eventos adversos e queixas técnicas no Brasil / Pharmacovigilance of compounded drugs - Part 2: Adverse event notifications and technical complaints in Brazil

Introdução: Medicamento manipulado é a preparação farmacêutica obtido por procedimento farmacotécnico a partir de uma prescrição de profissional habilitado destinada a um paciente individualizado ou cuja fórmula esteja inscrita no Formulário Nacional ou Internacional. Objetivo: Descrever o perfil das notificações relacionadas aos medicamentos manipulados, reportadas ao Sistema Nacional de Notificação em Vigilância Sanitária (Notivisa). Método: Estudo exploratório descritivo, retrospectivo ao período de 2006-2016 das notificações de medicamentos manipulados reportadas ao Notivisa. Os dados foram registrados e analisados no programa Excel versão para Windows 3.5.4. Resultados: De um total de 108.400 notificações referentes a medicamentos no período estudado, 335 (0,32%) foram relacionadas a notificações de medicamentos manipulados. As queixas técnicas (QT) obtiveram 90,40% das notificações, enquanto os eventos adversos (EA) obtiveram 9,60%. A Região Sudeste foi a principal notificadora (66,00%) e o estado de São Paulo, responsável por 54,00% do total das notificações. Os hospitais foram as instituições com maior frequência de notificação (81,00%). Foi possível avaliar os motivos que geraram as notificações, das quais as alterações relacionadas ao aspecto da preparação farmacêutica foram as predominantes dentre as QT, enquanto para os EA destacaram-se as reações adversas a medicamentos. Conclusões: As ocorrências observadas na farmacovigilância de medicamentos manipulados são próprias de cada produto com suas particularidades, embora o que se busque seja um padrão. Desta forma, tal observação poderá prevenir a ocorrência de danos à população exposta a situações semelhantes, se for devidamente notificada e amplamente divulgada.

Introduction: Compounded drug is a pharmaceutical preparation obtained by a pharmacotechnical procedure from a prescription of a qualified professional intended for an individualized patient, or whose formula is registered in the National or International Form. Objective: To describe the profile of notifications related to compounded drugs, reported to the National Health Surveillance Notification System (Notivisa). Method: Descriptive exploratory study, retrospective to the period 2006-2016, of the notifications of compounded drugs reported to Notivisa. Data were recorded and analyzed using the Excel program, version for Windows 3.5.4. Results: Of a total of 108,400 notifications referring to medicines in the studied period, 335 (0.32%) were related to reports of compounded drugs. Technical complaints (QT) obtained 90.40% of the notifications, while adverse events (AE) obtained 9.60%. The Southeast region was the main notifier (66.00%), and the state of São Paulo was responsible for 54.00% of the total notifications. Hospitals were the institutions with the highest frequency of notification (81.00%). It was possible to evaluate the reasons that generated the notifications, of which the changes related to the aspect of the pharmaceutical preparation were the predominant among the QT, while for the AEs, the adverse drug reactions stood out. Conclusions: The occurrences observed in the pharmacovigilance of compounded drugs are specific to each product with its particularities, although, what is sought is a pattern. In this way, such observation can prevent the occurrence of damages to the population exposed to similar situations, if it is duly notified and widely disseminated.

Development and characterization of photoprotective formulations containing keratin particles

This work deals with development and evaluation of MFQ protective formulation, which contains two organic filters, namely: octyl-p-methoxycinnamate (OMC) and benzophenone-3 (BP-3); a photostabilizing agent called ethylhexylmethoxycrylene (EHMCR) and keratin particles. The MFQ formulation was evaluated in order to measure its pH, spin-spin lattice relaxation time (T2H), occlusivity factor, formulation efficacy, photostability and skin permeation, as well as keratin particle properties. Keratin particle size increased when incorporated to formulation, however, it did not affect pH. The MFQ formulation was found to be photostable and photoprotective, as evidenced by sunlight photostability test, sun protection factor (SPF), UVA/UVB ratio and critical wavelength. Interaction between keratin particles and active substances (OMC, BP-3 and EHMCR) was evidenced by T2H measurements. Evidences suggest that keratin reduces the permeation of both UV filters employed along this study, therefore, it can be stated that keratin has a promising potential for use in sunscreen formulations.