RESUMEN

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

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RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Asunto(s)

Administración Rectal , Infecciones por VIH , Homosexualidad Masculina , Minorías Sexuales y de Género , Humanos , Masculino , Tailandia , Infecciones por VIH/prevención & control , Malaui , Minorías Sexuales y de Género/psicología , Estados Unidos , Adulto , Femenino , Adulto Joven , Sudáfrica , Homosexualidad Masculina/psicología , Supositorios , Adolescente , Perú , Prioridad del Paciente , Conducta Sexual , Personas Transgénero/psicología , Antiinfecciosos/administración & dosificación , Placebos/administración & dosificación , Formas de Dosificación

RESUMEN

Introducción: los medicamentos antitiroideos son una de las alternativas terapéuticas en el tratamiento de la enfermedad de Graves. Sin embargo, pueden generar efectos adversos severos poco frecuentes en el plano hematológico, como la anemia aplásica, la cual se ha asociado con altas dosis de estos medicamentos, aunque con reversión de esta afección ante el retiro del medicamento. Descripción del caso: mujer de 38 años con antecedente de enfermedad de Graves en tratamiento con metimazol, quien consultó por síntomas como epistaxis anterior de difícil control, petequias, astenia e hiporexia. Se documentó pancitopenia en el hemo-grama, con posterior hallazgo en biopsia de médula ósea de aplasia medular, sin respuesta ante el retiro del metimazol y soporte transfusional. Posteriormente, la paciente falleció. Conclusión: la presentación de aplasia medular asociada con metimazol es poco común y se relaciona con altas dosis de este medicamento. En la mayoría de casos, el retiro de este agente genera recuperación clínica y celular. No obstante, en algu-nos pacientes persiste el compromiso hematológico que va desde importantes repercusiones clínicas hasta desenlaces fatales. Por lo tanto, el presente caso busca hace hincapié en la importancia de vigilar este efecto adverso ante el inicio de esta medicación

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Introduction: Antithyroid drugs are one of the therapeutic alternatives in the treatment of Graves' dis-ease. However, it can generate severe but infrequent adverse effects at the hematological level, such as aplastic anemia, which has been associated with high doses of these drugs, although with reversal of this hematological condition when the drug is withdrawn. Case description: A 38-year-old woman with a his-tory of Graves' disease treated with methimazole, who consult for symptoms such as anterior epistaxis, petechiae, asthenia, and hyporexia. Pancytopenia is documented in the blood count, with a subsequent finding of bone marrow aplasia in bone marrow biopsy, without response to withdrawal of Methimazole and transfusion support. The patient subsequently died. Conclusion: The methimazole-associated bone marrow aplasia is uncommon and it ́s associated with high doses of methimazole, in most cases with-drawal of methimazole leads to clinical and cellular recovery. However, in some patients hematological involvement persists with significant clinical repercussions up to fatal outcomes. Therefore, this case seeks to highlight the importance of monitoring for this adverse effect before starting this medication

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Introdução: as drogas antitireoidianas são uma das alternativas terapêuticas no tratamento da doença de Graves. No entanto, pode causar efeitos adversos graves, mas infrequentes, no nível hematológico, como a anemia aplástica, que tem sido associada a altas doses desses medicamentos, embora com rever-são desse quadro hematológico quando a droga é retirada. Descrição do caso: mulher de 38 anos com história de doença de Graves tratada com metimazol, que consultou por sintomas como epistaxe ante-rior de difícil controle, petéquias, astenia e hiporexia. A pancitopenia é documentada no hemograma, com achado posterior de aplasia da medula óssea na biópsia da medula óssea, sem resposta à retirada do metimazol e suporte transfusional. O doente faleceu posteriormente. Conclusão: a apresentação de aplasia da medula óssea associada ao metimazol é pouco frequente em associação com doses elevadas de metimazol. Na maioria dos casos, a retirada do metimazol conduz à recuperação clínica e celular. No entanto, nalguns doentes, o envolvimento hematológico persiste com repercussões clínicas significati-vas, podendo mesmo ocorrer desfechos fatais. Assim, o presente caso pretende realçar a importância da monitorização deste efeito adverso antes de iniciar esta medicação

Asunto(s)

Humanos , Formas de Dosificación

RESUMEN

Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.

Asunto(s)

Polímeros , Tecnología Farmacéutica , Formas de Dosificación , Liberación de Fármacos , Polímeros/química , Impresión Tridimensional , Comprimidos/química , Tecnología Farmacéutica/métodos

RESUMEN

Two methods using LC-MS/MS were validated to quantify citalopram (CTP) racemate [(R/S)-CTP] and the enantiomers (R)-CTP and (S)-CTP in human plasma, respectively. Paroxetine hydrochloride was used as the internal standard, and samples were extracted by protein precipitation with acetonitrile. The non-enantioselective method was conducted using a C18 column, and the mobile phase consisted of water for solvent A and acetonitrile for solvent B, both with 0.1% formic acid. For the chiral method, an analytical column Lux Cellulose-1 was used. Mobile phase A was composed of water with 0.025% of formic acid and 0.05% of diethylamine, and mobile phase B consisted of acetonitrile:2-propanol (95:5, v/v). No significant matrix effects were observed at the retention times of analytes and internal standard. The mean recovery was 89%, and the assays were linear in the concentration range of 1-50 and 5-30 ng/mL for the non-enantioselective and enantioselective methods, respectively. The intra- and inter-day precisions of both methods were less than 12.30%, and the accuracies were less than 12.13%. The validated methods were successfully applied to a pharmacokinetic study in which 20-mg CTP tablets were administered to healthy volunteers, and their plasma levels were monitored over time in a bioequivalence study. HIGHLIGHTS: Simple and rapid LC-MS/MS method for the quantification of citalopram and its enantiomers in human plasma. Both methods were demonstrated to be selective, reliable, and sensitive. Both methods have sufficient sensitivity to quantify the steady state through concentrations already reported for citalopram and escitalopram. Validated method presented in this study can be suitably applied to pharmacokinetic studies involving citalopram and escitalopram. Bland-Altman analysis suggested that non-enantioselective and enantioselective methods can be applied in pharmacokinetic studies.

Asunto(s)

Cromatografía Liquida/métodos , Citalopram , Espectrometría de Masas en Tándem/métodos , Adolescente , Adulto , Citalopram/sangre , Citalopram/química , Citalopram/farmacocinética , Formas de Dosificación , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estereoisomerismo , Adulto Joven

RESUMEN

Abstract Simple, precise, accurate and specific spectrophotometric methods are progressed and validated for concurrent analysis of Furosemide (FUR) and Spironolactone (SPR) in their combined dosage form depend on spectral analysis procedures. Furosemide (FUR) in the binary mixture could be analyzed at its λmax 274 nm using its recovered zero order absorption spectrum using constant multiplication method (CM). Spironolactone (SPR) in the mixture could be analyzed at its λmax 238 nm by ratio subtraction method (RS). Concurrent determination for FUR and SPR in their mixture could be applied by amplitude modulation method (AM), absorbance subtraction method (AS) and ratio difference (RD). Linearity ranges of FUR and SPR were (2.0µg/mL-22.0 µg/mL) and (3.0µg/mL-30.0 µg/mL), respectively. Specificity of the proposed spectrophotometric methods was examined by analyzing the prepared mixtures in laboratory and was applied successfully for pharmaceutical dosage form analysis which have the cited drugs without additives contribution. The proposed spectrophotometric methods were also validated as per as the guidelines of ICH. Statistical comparison was performed between the obtained results with those from the official methods of the cited drugs, using one-way ANOVA, F-test and student t-test. The results are exhibiting insignificant difference concerning precision and accuracy

Asunto(s)

Espectrofotometría/métodos , Espironolactona/antagonistas & inhibidores , Preparaciones Farmacéuticas/administración & dosificación , Furosemida/antagonistas & inhibidores , Análisis de Varianza , Formas de Dosificación , Métodos

RESUMEN

Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPßCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability

Asunto(s)

Plastificantes/efectos adversos , Solubilidad , Ondansetrón/antagonistas & inhibidores , Pacientes/clasificación , Vómitos , Preparaciones Farmacéuticas/análisis , Náusea y Vómito Posoperatorios , Formas de Dosificación , Quimioterapia/instrumentación , Métodos , Películas Cinematográficas/clasificación

RESUMEN

O organogel é formado por uma matriz tridimensional composta de filamentos que se auto-organizam em uma rede entrelaçada e que, por seu tipo de estrutura, pode ser utilizado com o objetivo de atuar como um implante que se forma in situ, sendo capaz de se comportar como uma forma farmacêutica de liberação prolongada. Esse trabalho tem, por tanto, o objetivo desse trabalho foi desenvolver, caracterizar, quantificar e traçar perfis de dissolução para formulações de organogel contendo meloxicam como principio ativo. O material está dividido em quatro capítulos, sendo apresentada inicialmente (I) revisão da literatura a respeito da lecitina de origem vegetal, com suas principais fontes de obtenção, como soja, girassol e colza, e também seu uso farmacêutico na obtenção de formulações como organogéis, microemulsões e lipossomas. Os demais capítulos abordam (II) desenvolvimento e otimização de uma formulação de organogel contendo lecitina de soja e Pluronic® F-127 como formadores da matriz tridimensional e meloxicam como principio ativo. (III) Desenvolvimento e validação de um método de quantificação do teor de meloxicam por cromatografia líquida de alta eficiência (CLAE). (IV) Desenvolvimento de um método de dissolução para formulações de organogel, que fosse capaz de ser utilizado na caracterização do perfil de dissolução de diferentes formulações. Com os resultados obtidos, foi possível desenvolver formulações de organogel contendo lecitina de soja, Pluronic® F-127 e meloxicam, assim como um método analítico validado para as analises de teor. Por fim, foram obtidos também os perfis de dissolução de duas formulações mais promissoras

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Organogels are formed by a three-dimensional matrix composed of filaments that selforganize in an interlaced network and that, due to its type of structure, can be used with the objective of acting as an implant that forms in situ, being able to behave as an extendedrelease dosage form. This work has, therefore, the objective of this work was to develop, characterize, quantify and trace dissolution profiles for organogel formulations containing meloxicam as active ingredient. The material is divided into four chapters, initially presented (I) review of the literature on lecithin of plant origin, with its main sources of production, such as soybean, sunflower and rapeseed, and also its pharmaceutical use in obtaining formulations such as organogels , microemulsions and liposomes. The remaining chapters address (II) development and optimization of an organogel formulation containing soy lecithin and Pluronic® F-127 as three-dimensional matrix formers and meloxicam as an active ingredient. (III) Development and validation of a method for quantification of meloxicam content by high performance liquid chromatography (HPLC). (IV) Development of a dissolution method for organogel formulations, capable of being used to characterize the dissolution profile of different formulations. With the results obtained, it was possible to develop organogel formulations containing soy lecithin, Pluronic® F-127 and meloxicam, as well as a validated analytical method for content analysis. Finally, the dissolution profiles of two more promising formulations were also obtained

Asunto(s)

Preparaciones Farmacéuticas/análisis , Veterinarios , Drogas Veterinarias/análisis , Poloxámero/análisis , Disolución , Lecitinas/análisis , Meloxicam/antagonistas & inhibidores , Farmacéuticos/clasificación , Química Farmacéutica/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Formas de Dosificación , Métodos

RESUMEN

Abstract A stability indicating UPLC method has been developed and validated for the simultaneous determination of fosnetupitant and palonosetron in bulk and in injection dosage form. This combination is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeated courses of highly emetogenic chemotherapy for cancer. The chromatographic analysis was performed on an HSS, RP C18 column (2.1 x 100 mm, 1.8 µm) with an isocratic mobile phase composed of 0.25 M potassium dihydrogen orthophosphate buffer (pH 6.5), pH adjusted with dilute sodium hydroxide:acetonitrile (55:45 v/v), at a flow rate of 0.5 mL/min, and the eluents were monitored at an isosbestic point of 286 nm. The developed method was validated according to the ICH guidelines pertaining to specificity, precision, accuracy, linearity and robustness, and the stability indicating nature of the method was established by forced degradation studies. The retention times of fosnetupitant and palonosetron were observed at 1.390 and 2.404 min, respectively. The developed method proved to be accurate and precise. Linearity was established between 4.70 and 14.10 µg/mL for fosnetupitant and between 0.05 and 0.15 µg/mL for palonosetron. The LOD and LOQ were 0.115 and 0.385 µg/mL, respectively, for fosnetupitant, and 0.005 and 0.016 µg/mL, respectively, for palonosetron. Therefore, the proposed UPLC method was reliable, reproducible, precise and sensitive for the quantification of fosnetupitant and palonosetron.

Asunto(s)

Estudio de Validación , Palonosetrón/agonistas , Inyecciones/efectos adversos , Métodos , Diagnóstico , Formas de Dosificación , Concentración de Iones de Hidrógeno , Neoplasias/prevención & control

RESUMEN

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Asunto(s)

Comprimidos/clasificación , Preparaciones Farmacéuticas/análisis , Cromatografía Líquida de Alta Presión/métodos , Optimización de Procesos , Gestión de la Calidad Total/clasificación , Formas de Dosificación , Eplerenona/administración & dosificación , Torasemida/administración & dosificación

RESUMEN

Drugs of abuse are psychoactive substances illicitly distributed and used worldwide. In Rio de Janeiro, Brazil, they represent a public health issue and are directly related to several social problems. The recent increase in appearances of new psychoactive substances (NPS), derived from structural modifications of existing psychoactive substances, poses a threat to public health and forensic laboratories worldwide, as little is known about these substances. This study aimed to chemically and geographically map drugs of abuse from blotter papers seized by the Civil Police of Rio de Janeiro State (PCERJ) between 2006 and 2019. High-performance analytical techniques, such as gas chromatography-mass spectrometry (GC-MS) and Orbitrap mass spectrometry (Orbitrap-MS), combined with statistical analyses, were employed to characterize the seized samples. The most common chemical compounds in NPS found in this study were synthetic phenethylamines, i.e., molecules from the 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) and 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) families. Prior to 2014, the majority of seized blotter papers contained lysergic acid diethylamide (LSD) and were concentrated in the Metropolitan region. An upsurge in blotter paper seizures was observed from 2014 to 2017; the most common substances during this time were from the NBOMe family. NBOH compounds emerged in 2016 in coastal regions with high tourism, reaching over 1300 items only in 2017. Only one synthetic cannabinoid was found among the blotter papers seized in Rio de Janeiro between 2006 and 2019. The assembled chemical data and statistical analyses allowed the mapping and monitoring of the chemical profiles of the seized blotter papers, providing a strong foundation for the understanding of the origins and movement of these drugs around the RJ State.

Asunto(s)

Tráfico de Drogas/estadística & datos numéricos , Control de Medicamentos y Narcóticos/estadística & datos numéricos , Papel , Psicotrópicos/química , Brasil , Cannabinoides/química , Formas de Dosificación , Fentanilo/análogos & derivados , Fentanilo/química , Cromatografía de Gases y Espectrometría de Masas , Humanos , Estructura Molecular

RESUMEN

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 ºC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures

Asunto(s)

Comprimidos/farmacología , Preparaciones Farmacéuticas/análisis , Técnicas Microbiológicas/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Sensibilidad y Especificidad , Ámbar , Formas de Dosificación , Estabilidad de Medicamentos , Métodos

RESUMEN

Aminoglycosides are a relevant class of antibiotics widely used by medics and veterinaries. There are a variety of reasons that make their determination relevant, such as quality control, environment and food contamination assessment, drug-release studies, among others. The lack of a chromophore makes aminoglycoside spectrophotometric detection particularly challenging, often requiring derivatization. In this work, an indirect detection method, making use of imidazole as a probe, applying CZE was successfully tested. It did not require derivatization, which simplified the sample preparation. Suitable figures of merit were obtained; recoveries between 95 and 105%, adequate repeatability and precision, correlation coefficients (r) above 0.998, and limits of detection (LODs) of 3.2 and 11 mg/L for gentamicin and paromomycin, respectively. As a proof-of-concept, it was also applied in a simple controlled release experiment that was well fitted using the Hill equation.

Asunto(s)

Aminoglicósidos/análisis , Antibacterianos/química , Electroforesis Capilar/métodos , Espectrofotometría Ultravioleta/métodos , Formas de Dosificación , Imidazoles/química , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados

RESUMEN

Controlled release is of vital relevance for many drugs; thus, there is a keen interest in materials that can improve the release profiles of formulations administered via buccal, transdermal, ophthalmic, vaginal, and nasal. The desirable effects of those materials include the improvement of stability, adhesiveness, solubility, and retention time. Hence, different synthetic and natural polymers are utilized to achieve these objectives. In this respect, xanthan gum is an anionic polysaccharide that can be obtained from Xanthomonas bacteria. It is a natural polymer broadly employed in numerous food products, lotions, shampoos, and dermatological articles. Furthermore, due to its physicochemical features, xanthan gum is growingly utilized for the development and improvement of drug delivery systems. In this regard, encouraging findings have been revealed by recent formulations for pharmaceutical applications, including antiviral carriers, antibacterial transporters, transdermal patches, vaginal formulations, and anticancer medications. In this article, we perform a concise description of the chemical properties of xanthan gum and its role as a modifier of drug release. Furthermore, we present an outlook of the state of the art of research focused on the utilization of xanthan gum in varied pharmaceutical formulations, which include tablets, films, hydrogels, and nanoformulations. Finally, we discuss some perspectives about the use of xanthan gum in these formulations.

Asunto(s)

Liberación de Fármacos , Polisacáridos Bacterianos/química , Animales , Preparaciones de Acción Retardada , Formas de Dosificación , Humanos , Hidrogeles/química , Nanopartículas/química

RESUMEN

Praziquantel (PZQ) is a highly effective low-cost anthelmintic agent used as the first-choice treatment against schistosomiasis. The low solubility of the active is a major drawback for pharmaceutical formulation. A valid approach of the pharmaceutical industry for the improvement of the pharmacotechnical features of the active principles (such as solubility, processability, stability, among others), is the preparation of new solid forms, such as salts, polymorph, and pseudo-polymorph. Herein we report the preparation and characterization of a new solid form PZQ. The PZQ monohydrate (PZQ-MH) was prepared by a solventless procedure from the commercial racemate and the product was characterized at the solid-state employing optical digital microscopy, thermal methods (melting point, differential scanning calorimetry and thermogravimetric analysis), as well as and mid-infrared and near infrared spectroscopies. The chemical structure and content of water were full assessed by 1H nuclear magnetic resonance (NMR) in solution. The amount of water in PZQ-was also determined by different approaches, including thermogravimetric analysis and the loss on drying test. Solid-state 13C NMR (ssNMR) and X-ray powder diffraction (XRPD) completed the structural characterization of the new monohydrate. PZQ-MH showed a crystalline behavior during XRPD experiments and showed relevant differences in spectroscopic, calorimetric, ssNMR and XRPD signals when it was compared with the known crystal (Form A) and amorphous forms of PZQ. The determination of the intrinsic dissolution rate (IDR) of PZQ-MH was carried out as a functional characterization, observing that the new form had slightly higher IDR than Form A.

Asunto(s)

Antihelmínticos/química , Formas de Dosificación , Praziquantel/química , Rastreo Diferencial de Calorimetría , Espectroscopía de Resonancia Magnética con Carbono-13 , Difracción de Polvo , Espectroscopía de Protones por Resonancia Magnética , Solubilidad

RESUMEN

Our research group has pioneered the development of liquisolid pellets as a new drug delivery system targeting at the improvement of the dissolution rates of poorly water-soluble drugs, combining the technological and biopharmaceutical advantages of both multiparticulate and liquisolid systems. Recently, Lam and collaborators claimed the invention of "liqui-pellets" as "the emerging next-generation oral dosage form which stems from liquisolid concept in combination with pelletization technology". However, the concept of liqui-pellet is not novel. As we demonstrate in this commentary, liqui-pellets are the same type of preparation as our previously and extensively reported liquisolid pellets. Liquisolid pellets have been disclosed in a patent application and public peer-reviewed articles covering the concept, preparation and challenges associated with these systems. There are no technical differences that justify excluding our previous reports as the first reports on liquisolid pellets or liqui-pellets. This commentary highlights the similarities between liquisolid pellets and liqui-pellets, focusing on the anteriority of liquisolid pellets as disclosed by our group.

Asunto(s)

Formas de Dosificación , Biofarmacia , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Implantes de Medicamentos

RESUMEN

Siparuna guianensis (Laurales: Siparunaceae) has a terpene-rich essential oil with great potential for larvicides. The poor water miscibility of their compounds makes nano-emulsions of great interest for novel bioactive systems, including for control of Aedes aegypti (Diptera: Culicidae). This species is adapted to urban environments with important role in the epidemiology of some arboviruses such as dengue, chikungunya fever, zika, and urban yellow fever. The aim of the present study was to evaluate the feasibility of nano-emulsification to affect Ae. aegypti larvae. An optimal system was achieved by using a nonionic single surfactant, highlighted by its satisfactory size distribution profile. Moreover, improved larvicidal activity in comparison to bulk essential oil can be observed for the nano-emulsions. The estimated LC50 and LC90 values after 24 h of treatment of larvae with the essential oil were, respectively, 86.5232 and 134.814 µg/ml, while the estimated LC50 and LC90 value after treatment with the nano-emulsion were 24.7572 and 75.2452 µg/ml, respectively. The utilization of a simple technique to produce a fine nano-emulsion opens perspective for further integrative practices of mosquito control and giving value to this Amazon plant species may encourage its sustainable use and contribute to conservation policies.

Asunto(s)

Aedes , Insecticidas/análisis , Laurales/química , Aceites Volátiles/química , Animales , Formas de Dosificación , Dosificación Letal Mediana , Nanoestructuras , Aceites Volátiles/administración & dosificación

RESUMEN

The aim of this work was to perform solubility studies for fexofenadine hydrochloride and establish dissolution conditions for this drug in oral suspension dosage form. The solubility study was executed through the shake-flask method, below 37 ºC±1 ºC, at 100 rpm stirring for 12 h in three buffer solutions: hydrochloric acid pH 2.0, acetate pH 4.5 and phosphate pH 6.8. The dissolution test was developed in vessels containing 900 mL of the same buffer, employing the paddle apparatus in speed of 25 and 50 rpm, below 37 ºC±0.5 ºC. The drug was classified as low solubility according to the Biopharmaceutics Classification System, since the dose/solubility ratio was higher than 250 mL in all media tested (326.55 mL in buffer pH 2.0; 2,456.33 mL in buffer pH 4.5 and 1,021.16 mL in buffer pH 6.8). The dissolution test showed that a release of 85% in 30 min could be established. The rotation speed of 25 rpm, media volume of 900 mL and insertion of the samples through weighted syringes are adequate. The buffered media pH 2.0 could be chosen as dissolution media.

Asunto(s)

Solubilidad , Suspensiones/farmacología , Disolución/métodos , Biofarmacia , Preparaciones Farmacéuticas/análisis , Cromatografía Líquida de Alta Presión/métodos , Formas de Dosificación

RESUMEN

Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Measuring devices were packaged with their respective product. Drug content uniformity was assessed to each substance according to pharmacopeial methods. Tablets subdivided by splitter had the poorest performance among all approaches, in which doses ranged around 60% of the labeled amount (Acceptance Value = 58.1 and RSD = 23.2%). The greatest performances were observed for the dosing syringe which fulfilled all the requirements for dose precision and for the glass dropper bottle. There were significant differences in dose delivery between manufacturers of the same medicine when measuring the same volume or number of drops. High drug content variability is extremely harmful to pharmacotherapy and may result in therapeutic failure or toxicity. It is crucial that measuring devices and scoring of tablets be checked for functionality and standardized for different manufacturers of the same medicine. Part of the approaches for achieving individual dosing did not meet the quality needs for drug content and uniformity. Yet, our findings show that more accurate and precise dosing can be accessed when using the dosing syringe and glass dropper bottle.

Asunto(s)

Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/normas , Formas de Dosificación/normas , Sistemas de Liberación de Medicamentos/métodos , Control de Calidad , Jeringas/normas , Administración Oral , Anciano , Niño , Relación Dosis-Respuesta a Droga , Humanos , Comprimidos

RESUMEN

BACKGROUND: Tablet splitting appears common in older adults, but its safety, and the factors associated with this practice, remain unclear. OBJECTIVE: To identify which psychotropic drugs are most often split, which doses are intended with this practice, and whether these doses are provided by the Brazilian Unified Health System (SUS) or commercially available. METHODS: Cross-sectional descriptive study of 632 geriatric outpatients. The number of individuals who split tablets was identified, as well as the psychotropic drugs they used and split. The availability of these drugs on the SUS network and on the market was assessed by checking the 2017 National Formulary of Essential Medicines (RENAME 2017) and the Dictionary of Proprietary Medicinal Products (Dicionário de Especialidades Farmacêuticas) respectively. RESULTS: Tablet splitting was reported by 178 patients (28.2%). This practice was significantly more common among those aged 80 years or older. Tablet splitting was significantly associated with a greater number of medical visits and a higher pill burden. The most commonly affected therapeutic classes were antipsychotics (23.9%), other psychotropic drugs (18.7%) and antidepressants (12.3%). Of the 20 psychotropic drugs split, 45% were available on the SUS. CONCLUSIONS: Tablet splitting poses a challenge, as there is no guarantee of uniformity of concentration of the active ingredient in the split halves. Although the psychotropic drugs that were split in this sample are commercially available, most were not available from SUS in the desired dose forms for older adults.

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INTRODUÇÃO: O fracionamento de comprimidos é comum em pacientes geriátricos, mas a segurança e os fatores associados a essa prática permanecem incertos. OBJETIVO: Identificar quais medicamentos psicotrópicos são mais frequentemente fracionados, quais doses se destinam a essa prática e se essas dosagens são fornecidas pelo Sistema Único de Saúde (SUS) ou comercialmente disponíveis. MÉTODOS: Estudo descritivo transversal de 632 pacientes ambulatoriais geriátricos. O número de indivíduos que fracionou os comprimidos foi identificado, bem como os medicamentos psicotrópicos que foram usados e fracionados. A disponibilidade desses medicamentos na rede SUS e no mercado foi avaliada através da verificação do Formulário Nacional de Medicamentos Essenciais (RENAME) de 2017 e do Dicionário de Especialidades Farmacêuticas, respectivamente. RESULTADOS: A partição de comprimidos foi relatada por 178 pacientes (28,2%). Essa prática foi significativamente mais comum entre aqueles com 80 anos ou mais. O fracionamento dos comprimidos foi significativamente associado a um maior número de consultas médicas e a uma maior carga de comprimidos. As classes terapêuticas mais comumente afetadas foram antipsicóticos (23,9%), outros medicamentos psicotrópicos (18,7%) e antidepressivos (12,3%). Dos 20 medicamentos psicotrópicos fracionados, 45% estavam disponíveis no SUS. CONCLUSÕES: O fracionamento de comprimidos representa um desafio, pois não há garantia de uniformidade de concentração do ingrediente ativo nas metades fracionadas. Embora os medicamentos psicotrópicos fracionados nesta amostra estejam disponíveis comercialmente, a maioria não estava disponível no SUS nas formas de dosagem desejadas para a população geriátrica.

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Psicotrópicos/administración & dosificación , Antipsicóticos/administración & dosificación , Medicamentos Esenciales/administración & dosificación , Medicamentos Fraccionados , Antidepresivos/administración & dosificación , Pacientes Ambulatorios , Salud del Anciano , Estudios Transversales , Formas de Dosificación

RESUMEN

Neglected tropical diseases (NTDs) constitute a group of infectious diseases prevalent in countries with tropical and subtropical climate that affect the poorest individuals and produce high chronic disability associated with serious problems for the health system and socioeconomic development. Chagas disease or American trypanosomiasis is included on the NTDs list. However, even though this disease affects more than 10 million people, mostly in Latin America, causing the death of over 10,000 people every year, only two drugs are approved for its treatment, benznidazole and nifurtimox. These antiparasitic agents were developed almost half a century ago and present several biopharmaceutical disadvantages such as low aqueous solubility and permeability limiting their bioavailability. In addition, both therapeutic agents are available only as tablets and a liquid pediatric formulation is still lacking. Therefore, novel pharmaceutical strategies to optimize the pharmacotherapy of Chagas disease are urgently required. In this regard, nanotechnological approaches may be a crucial alternative for the delivery of both drugs ensuring an effective pharmacotherapy although the successful bench-to-bedside translation remains a major challenge. The present work reviews in detail the formulation and in-vitro/in-vivo analysis of different nanoformulations of nifurtimox and benznidazole in order to enhance their solubility, dissolution, bioavailability and trypanocidal activity.

Asunto(s)

Enfermedad de Chagas/tratamiento farmacológico , Nanoestructuras , Nifurtimox/uso terapéutico , Nitroimidazoles/uso terapéutico , Tripanocidas/uso terapéutico , Formas de Dosificación , Humanos , Nifurtimox/administración & dosificación , Nifurtimox/química , Nitroimidazoles/administración & dosificación , Nitroimidazoles/química , Tripanocidas/administración & dosificación , Tripanocidas/química