Diagnosis of Celiac Disease after Starting Antitubercular Medication: A Case Report

We present the case of a young patient from Argentina living in a rural area without any relevant medical history. He consulted the emergency department after blunt chest trauma, and during trauma studies, images compatible with pulmonary tuberculosis were found, a diagnosis made incidentally. After starting treatment, he exhibited gastrointestinal symptoms such as diarrhea, abdominal pain, and weight loss, which were initially considered an adverse effect of treatment with rifampin/isoniazid/pyrazinamide/ethambutol (RHZE). Upon completing the first phase of treatment and suspending the medication, the symptoms improved, and the bacilloscopies were negative. Subsequently, the severity of the symptoms drew attention. Additional paraclinical tests were performed with malabsorptive diarrhea results, considering the patient's origin and the fact that his diet included products that he grew himself without prior exposure to gluten. Celiac disease is suspected, and antibodies and biopsy results compatible with this entity were obtained. When reviewing the association of symptom onset with the RHZE/pyridoxine treatment, we found these medications may have wheat-based excipients, which explains the worsening of symptoms, not due to the gastrointestinal adverse effects of the antibiotic but its excipients. Finally, the case was analyzed, tuberculosis was ruled out, and treatment was suspended, refocusing the therapeutic effort on recovering the patient's nutritional status. Subsequently, no other hospital admissions were recorded, and he remained respiratorily asymptomatic, with weight gain and nutritional recovery.

Se presenta el caso de un paciente joven, proveniente de Argentina y residente de un área rural, sin ningún antecedente médico a resaltar. Consultó al servicio de urgencias después de un trauma cerrado de tórax y durante los estudios de trauma se encontraron imágenes compatibles con tuberculosis pulmonar, diagnóstico realizado de manera incidental. Luego del inicio de tratamiento presentó síntomas gastrointestinales dados por diarrea, dolor abdominal y pérdida de peso, lo que inicialmente se consideró un efecto adverso al tratamiento con rifampicina/isoniazida/pirazinamida/etambutol (RHZE). Al completar la primera fase del tratamiento y suspender la medicación mejoraron los síntomas, además de que las baciloscopias fueron negativas. Posteriormente, llamó la atención la gravedad de los síntomas, por lo que se realizaron paraclínicos adicionales con resultados a favor de diarrea malabsortiva; teniendo en cuenta la procedencia del paciente y el hecho de que basaba su dieta en productos que él mismo cultivaba, sin haber exposición previa al gluten. Se sospecha enfermedad celíaca, y se obtuvieron anticuerpos y resultados en la biopsia compatibles con esta entidad. Al revisar la asociación de inicio de síntomas con el uso de tratamiento de RHZE/piridoxina, se observa que estos medicamentos pueden tener excipientes a base de trigo, lo que explica el empeoramiento de los síntomas, no por efectos adversos gastrointestinales del antibiótico sino por sus excipientes. Finalmente, se analizó el caso, se descartó tuberculosis y se suspendió el tratamiento, redirigiendo el esfuerzo terapéutico hacia la recuperación del estado nutricional del paciente. Posteriormente, no se registran otros ingresos hospitalarios, continúa asintomático respiratorio, con ganancia de peso y recuperación nutricional.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non–IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations.To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. (AU)

El término alergia ocular engloba un conjunto de enfermedades inflamatorias de la superficie ocular de origen inmunoalérgico, con distintos niveles de afectación y gravedad. Están causadas por una variedad de mecanismos inmunes, mediados o no por IgE y pueden involucrar a todos los componentes de la superficie ocular, incluyendo conjuntiva, córnea, párpados, película lagrimal y flora comensal. De estos trastornos, el más común es la enfermedad alérgica conjuntival. En su clasificación se incluyen distintas formas clínicas según el nivel de afectación y la presencia o no de cambios proliferativos en la conjuntiva palpebral, asociación con dermatitis atópica, y estímulos mecánicos por cuerpo extraño, incluyendo lentes de contacto. Las guías terapéuticas para el tratamiento de la conjuntivitis alérgica proponen un tratamiento escalonado, tanto en administración oftálmica como oral, en función de la gravedad de los síntomas, las comorbilidades alérgicas del paciente y el logro de un control adecuado. En general, cuando los síntomas oculares predominan o se presentan de forma aislada, se prefieren las formulaciones oftálmicas de antihistamínicos de administración tópica y, dentro de estas, los colirios. Para mantener el equilibrio de la superficie ocular, las formulaciones tópicas oftálmicas deben mostrar una buena tolerancia. El objetivo principal de este artículo es revisar las características y otras propiedades de los excipientes (conservantes, tampones, agentes para ajustar el pH, viscosizantes, agentes humectantes o cosolventes, antioxidantes, isotonizantes y osmoprotectores) y sustancias activas (antihistamínicos oculares) que deben ser considerados cuando se formulan los preparados de administración tópica oftálmica de agentes antihistamínicos. (AU)

Control de carbohidratos en los medicamentos antiepilépticos para niños con dieta cetogénica / Controlling carbohydrate content in antiepileptic medications for children on a ketogenic diet

Introducción: los pacientes que siguen una dieta cetogénica para el control de las crisis epilépticas deben llevar a cabo un estricto control de los hidratos de carbono procedentes tanto de los alimentos que consumen como de los medicamentos que tienen pautados. Tanto en la instauración de la dieta cetogénica como cuando el médico prescribe un medicamento nuevo es necesario el ajuste de la medicación a las formas farmacéuticas más adecuadas, de forma que se minimice el aporte de excipientes en forma de hidratos de carbono de los medicamentos.Objetivos:el objetivo que planteamos en el presente trabajo fue elaborar un listado de medicamentos antiepilépticos de utilización habitual en neurología pediátrica que incluyera información sobre su contenido calórico en forma de hidratos de carbono para la administración a pacientes con dieta cetogénica.Métodos:en cada medicamento incluido en el listado se revisó el contenido en excipientes considerados hidratos de carbono y derivados que pudieran influir en la cetosis del paciente. Se calculó el contenido calórico procedente de los hidratos de carbono y polioles de cada medicamento.Resultados:elaboración de una tabla para consulta del contenido calórico de distintos medicamentos antiepilépticos utilizados en neurología pediátrica para pacientes con dieta cetogénica.Conclusiones:la tabla publicada pretende ser una herramienta útil que permita la consulta del contenido calórico de distintos medicamentos antiepilépticos y la selección del medicamento idóneo que menos afecte a la dieta cetogénica. Con el contenido calórico en carbohidratos de las medicaciones pautadas se podrán realizar los ajustes necesarios en la dieta para mantener la cetosis necesaria. (AU)

Introduction: patients who follow a ketogenic diet for the control of epileptic seizures must carry out a strict control of carbohydrates from the foods they eat and the medicines they are prescribed. In the initiation of a ketogenic diet and when a doctor prescribes a new medication, it is necessary to select the most appropriate pharmaceutical form so that the supply of excipients in the form of carbohydrates from the drugs is minimized.Objectives:the goal of the present paper was to compile a list of carbohydrate and caloric contents in antiepileptic drugs commonly used in pediatric neurology.Methods:in each medication included in the list, the content of excipients considered carbohydrates and derivatives that could influence the patient's ketosis was reviewed. The caloric content from carbohydrates and polyols in each medication was calculated.Results:the table provides the total carbohydrate and caloric content for antiepileptic medications in pediatric patients consuming the ketogenic diet.Conclusions:this table is intended to be a useful tool to help clinicians select a pharmaceutical form that is less likely to affect the ketogenic diet. Additionally, knowing the carbohydrate content of a new medication will allow adjustment of the diet to maintain ketosis. (AU)

[Controlling carbohydrate content in antiepileptic medications for children on a ketogenic diet]. / Control de carbohidratos en los medicamentos antiepilépticos para niños con dieta cetogénica.

Introduction: Introduction: patients who follow a ketogenic diet for the control of epileptic seizures must carry out a strict control of carbohydrates from the foods they eat and the medicines they are prescribed. In the initiation of a ketogenic diet and when a doctor prescribes a new medication, it is necessary to select the most appropriate pharmaceutical form so that the supply of excipients in the form of carbohydrates from the drugs is minimized. Objectives: the goal of the present paper was to compile a list of carbohydrate and caloric contents in antiepileptic drugs commonly used in pediatric neurology. Methods: in each medication included in the list, the content of excipients considered carbohydrates and derivatives that could influence the patient's ketosis was reviewed. The caloric content from carbohydrates and polyols in each medication was calculated. Results: the table provides the total carbohydrate and caloric content for antiepileptic medications in pediatric patients consuming the ketogenic diet. Conclusions: this table is intended to be a useful tool to help clinicians select a pharmaceutical form that is less likely to affect the ketogenic diet. Additionally, knowing the carbohydrate content of a new medication will allow adjustment of the diet to maintain ketosis.

Introducción: Introducción: los pacientes que siguen una dieta cetogénica para el control de las crisis epilépticas deben llevar a cabo un estricto control de los hidratos de carbono procedentes tanto de los alimentos que consumen como de los medicamentos que tienen pautados. Tanto en la instauración de la dieta cetogénica como cuando el médico prescribe un medicamento nuevo es necesario el ajuste de la medicación a las formas farmacéuticas más adecuadas, de forma que se minimice el aporte de excipientes en forma de hidratos de carbono de los medicamentos. Objetivos: el objetivo que planteamos en el presente trabajo fue elaborar un listado de medicamentos antiepilépticos de utilización habitual en neurología pediátrica que incluyera información sobre su contenido calórico en forma de hidratos de carbono para la administración a pacientes con dieta cetogénica. Métodos: en cada medicamento incluido en el listado se revisó el contenido en excipientes considerados hidratos de carbono y derivados que pudieran influir en la cetosis del paciente. Se calculó el contenido calórico procedente de los hidratos de carbono y polioles de cada medicamento. Resultados: elaboración de una tabla para consulta del contenido calórico de distintos medicamentos antiepilépticos utilizados en neurología pediátrica para pacientes con dieta cetogénica. Conclusiones: la tabla publicada pretende ser una herramienta útil que permita la consulta del contenido calórico de distintos medicamentos antiepilépticos y la selección del medicamento idóneo que menos afecte a la dieta cetogénica. Con el contenido calórico en carbohidratos de las medicaciones pautadas se podrán realizar los ajustes necesarios en la dieta para mantener la cetosis necesaria.

Avaliação de cinco excipientes no perfil de dissolução de cápsulas magistrais de naproxeno / Evaluation of five excipients in the profile of dissolution of naproxen magisterial capsules

Introdução: o naproxeno é um anti-inflamatório não esteroidal (AINE) encontrado nas formas farmacêuticas cápsulas e comprimidos. A análise do efeito de diferentes tipos de excipientes na formulação representa uma importante ferramenta no que diz respeito à influência na dissolução. Objetivo: analisar o efeito de diferentes tipos e quantidades de excipientes no perfil de dissolução de cápsulas de naproxeno. Material e Método: foram manipuladas 4 fórmulas de cápsulas de naproxeno na concentração de 250 mg, com variações de excipientes quanto às concentrações de diluentes, molhantes e desintegrantes. No teste de dissolução, foram avaliadas 6 unidades de cada formulação, em tampão fosfato pH 7,4 (900mL), aparato pá + sinker, 50 rpm, em 6 diferentes tempos de coleta, com leitura das amostras obtidas em 332 nm. Para a determinação da porcentagem de princípio ativo liberado em função do tempo no teste de perfil de dissolução, foi previamente construída uma curva de calibração com 5 concentrações diferentes. Segundo USP (2013), a porcentagem mínima de dissolução de comprimidos de naproxeno aos 45 minutos é de no mínimo 80%. Resultados: todas as formulações se encontram dentro das especificações farmacopéicas, sendo que a formulação 1 apresentou melhor perfil de dissolução do naproxeno, além de ser a formulação com menor custo de preparo, constatando a influência da quantidade e do tipo de excipiente. Conclusão: a melhor combinação dos tipos e quantidades de excipientes em uma formulação magistral é essencial para garantir a qualidade e a eficácia dos fármacos manipulados, especialmente os Classe II no Sistema de Classificação Biofarmacêutica.

Introduction: Naproxen is a Nonsteroidal Anti-Inflammatory drugs (NSAIDs) found in pharmaceutical forms capsules and tablets. The analysis of the effect with different kinds of excipients in magistral formulation represents an important tool to the influence on the dissolution. Purpose: to analyze the effect of different kinds and amounts of excipients on the dissolution profile of naproxen capsules. Material and Method: 4 naproxen capsule formulations in the 250 mg concentration were manipulated, with excipient variations regarding concentrations of diluents, wetting agents and disintegrants. In the dissolution test, 6 units of each formulation were evaluated in phosphate buffer pH 7.4 (900mL), paddle + sinker apparatus, 50 rpm, in 6 different collection times, with a reading of the samples obtained at 332 nm. For percentage determination of active principle released in function of time in dissolution profile test, a calibration curve with 5 different concentrations was previously constructed. According to USP (2013), the minimum dissolution rate of naproxen tablets at 45 minutes is at least 80%. Results: all formulations are within pharmacopoeial specifications, and formulation 1 presented a better dissolution profile of naproxen, besides being the formulation with the lowest preparation cost, noting the influence of the amount and type of excipient. Conclusion: The best combination of the kinds and amounts of excipients in a magistral formulation is essential to ensure the quality and efficacy of the drugs handled, especially Class II in the Biopharmaceutical Classification System.

Presença de lactose em medicamentos isentos de prescrição / Presence of lactose in nonprescription drugs

Introdução: a polifarmácia e a automedicação estão presentes na população brasileira, sendo frequente sua ocorrência com medicamentos isentos de prescrição. Ademais, a lactose é utilizada como excipiente em formas farmacêuticas sólidas. Objetivo: o presente estudo constitui uma pesquisa sobre lactose, na condição de excipiente, em medicamentos isentos de prescrição (MIPs). Metodologia: em 391 MIPs presentes em cinco formas farmacêuticas sólidas e analisadas por classes, categorias e marcas, foram coletadas, nos meses de abril e maio de 2018, informações quanto à presença de lactose em bulas disponíveis nos sites da Agência Nacional de Vigilância Sanitária e da indústria farmacêutica no Brasil. Resultados: constatou-se que a lactose está presente em 43,48% dos MIPs, sendo mais frequente nos comprimidos e comprimidos revestidos, nas proporções de 42,94% e 36,47%, respectivamente. Ela foi encontrada, predominantemente, em medicamentos similares, principalmente antialérgicos, analgésicos não opioides e anti-inflamatórios não esteroides, bem como na totalidade dos antidiarreicos e laxantes. Das 88 marcas analisadas, 30 apresentaram mais de 50% dos produtos com lactose. Identificou-se um percentual expressivo de medicamentos utilizados no controle dos sintomas de intolerância à lactose que continham esse carboidrato como excipiente. Conclusão: nas formas farmacêuticas analisadas, a presença de lactose nos MIPs é superior a 40%. A lactose presente pode ser agravante de sintomas gastrintestinais. Portanto, é essencial incluir, na embalagem dos medicamentos, a frase de alerta sobre a presença desse açúcar, visando à sua ampla divulgação, particularmente dirigida aos indivíduos com restrição de uso dessa substância.

Introduction: polypharmacy and self-medication are present in Brazilian population, frequently occurring for prescription-free medicines. In addition, lactose is used as an excipient in solid dosage forms of prescription-free medicines. Objective: the present study constitutes a research on lactose, as an excipient, in prescription-free medicines (MIPs). Methodology: in 391 MIPs present in five solid dosage pharmaceutical forms and analyzed by classes, categories and brands, in April and May 2018, information was collected on the presence of lactose in the package inserts available on the websites of the National Sanitary Surveillance Agency and on the pharmaceutical industry websites in Brazil. Results: it was found that lactose is present in 43.48% of the MIPs, being more frequent in tablets and coated tablets, in the proportions of 42.94% and 36.47%, respectively. It has been found predominantly in similar drugs, mainly antiallergics, non-opioid analgesics and non-steroidal anti-inflammatory drugs, as well as in all antidiarrheals and laxatives. Of the 88 brands analyzed, 30 presented over 50% of lactose products. An expressive percentage of drugs used to control the symptoms of lactose intolerance that contained this carbohydrate as an excipient were identified. Conclusion: in the pharmaceutical forms analyzed, the presence of lactose in the MIPs is higher than 40%. The lactose present may be aggravating gastrointestinal symptoms. It is therefore essential to include a warning on the presence of this sugar on the packaging of medicinal products, with a view to their wide dissemination, particularly for those who have a restricted use of that substance.

Cytotoxic and genotoxic potential of Ginkgo biloba L, in industrialized and without-additive forms / Potencial citotóxico e genotóxico de Ginkgo biloba L, nas formas industrializada e não aditivada

The toxic potential at the cellular level of industrialized Ginkgo biloba L. leaves was evaluated in meristematic cells of Allium cepa at concentrations of 0.1; 0.2 and 0.4 mg/ml. The industrialized products, from four pharmaceutical laboratories, were identified as A, B, C and D. Cell-level toxicity of dehydrated ginkgo leaf tea was also evaluated at concentrations of 0.15; 0.30 and 0.60 mg/ml. Dehydrated products were purchased from herbalists certified by ANVISA. The roots were exposed to teas and processed products for 24 and 48 hours. The results were submitted to the Chi-square test at 5%. However, industrialized ginkgo products at all concentrations caused antiproliferative effect. Also, the products purchased in pharmacies did not induce significant changes to root meristems. Therefore, industrialized ginkgo promoted cytotoxicity, however, they were not genotoxic to the bioassay used.

Avaliou-se, em células meristemáticas de raízes de Allium cepa, o potencial tóxico em nível celular de folhas de Ginkgo biloba L. industrializadas, nas concentrações 0,1; 0,2 e 0,4 mg/mL. Os produtos industrializados, oriundos de quatro laboratórios farmacêuticos, foram identificados como A, B, C e D. Também avaliou-se a toxicidade em nível celular de chás de folhas de ginkgo desidratadas, nas concentrações 0,15; 0,30 e 0,60 mg/mL. Os produtos desidratados foram adquiridos em ervanários certificados pela ANVISA. As raízes ficaram expostas aos chás e produtos industrializados por 24 e 48 horas. Os resultados obtidos foram submetidos ao teste Qui-quadrado, a 5%. No entanto, os produtos de ginkgo industrializados, em todas as concentrações, causaram efeito antiproliferativo. Ainda, os produto adquiridos em farmácias não induziram alterações em número significativo aos meristemas de raízes. Portanto, os ginkgos industrializados promoveram citotoxicidade, porém, não foram genotóxicos frente ao bioensaio utilizado.

[What medication should be prescribed to a patient with coeliac disease?] / ¿Qué medicamento prescribiría a un paciente con enfermedad celiaca?

Coeliac disease is a permanent intolerance to gluten proteins from wheat, rye, barley and triticale. Although strict adherence is complicated, the only effective treatment is a gluten-free diet throughout life. Some drugs contain starch as an excipient, and there is a risk related to the gluten content, which must be avoided in these patients. Current legislation requires the analysis of the protein content of wheat starch, or the absence of starches from another source where rice, maize, or potato starches are used as excipients. But, it does not specify that reference should be made to traces of gluten that are residues of the process of production of the active ingredient. As regards the case described, there needs to be awareness of the importance of adequately informing patients and reviewing/updating current legislation to ensure the safe use of drugs.

Propuesta de actualización de las normas de la Junta Revisora de productos farmacéuticos, capitulo XI de los excipientes para las formas farmacéuticas líquidas oreales / Proposal to update the rules of the Review Board of pharmaceutical products, chapter XI of the excipients for the oral liquid dosage forms

Al momento de desarrollar un nuevo medicamento, la forma farmacéutica toma gran importancia representando un gran reto, la selección de los excipientes adecuados para obtener un producto que no se vea afectado en sus características organolépticas, ni físico químicas. La Autoridad Regulatoria implementa a través de normas y/o publicaciones oficiales, concentraciones, límites y advertencias para su empleo en la formulación. En el país rigen las Normas de la Junta Revisora de Productos Farmacéuticos, con el fin de obtener productos farmacéuticos que cumplan con estándares de calidad, seguridad y eficacia, lo que implica la necesidad de actualizar las Normas mencionadas, que datan del año 1998, en este estudio, el Capítulo XI "De los excipientes", aplicado a las formas farmacéuticas líquidas orales. La investigación se efectuó mediante análisis de fuentes secundarias de excipientes contemplados en la normativa nacional e internacional, a efecto de determinar comparación y vigencia; una vez analizadas se elaboró una lista en la cual se actualizan los excipientes. Una vez realizada la comparación de las dos listas de excipientes, se identificó los excipientes utilizados a nivel internacional y se procedió a la elaboración de la Lista de Excipientes ajustado a la necesidad actual.

At the time of developing a new drug, the pharmaceutical form is of great importance representing a great challenge, the selection of suitable excipients to obtain a product that is not affected in its organoleptic or physical chemical characteristics. The Regulatory Authority implements, through standards and / or official publications, concentrations, limits and warnings for its use in the formulation. In order to obtain pharmaceutical products that comply with quality, safety and efficacy standards, the Standards of the Pharmaceutical Products Review Board are in place, which implies the need to update the mentioned Standards, which date from 1998, in This study, Chapter XI "Of the excipients", applied to oral liquid pharmaceutical forms. The investigation was carried out by means of analysis of secondary sources of excipients contemplated in the national and international regulations, in order to determine comparison and validity; once analyzed a list was prepared in which the excipients are updated. After comparing the two lists of excipients, the excipients used at the international level were identified and the List of Excipients adjusted to the current need was drawn up.

Determination of phosphate concentration and pH in artificial tear drops. / Determinación de la concentración de fosfatos y pH en los colirios de lágrima artificial.

OBJECTIVE: To determine phosphate concentration and pH in artificial tear eye drops commercially available in Spain. MATERIALS AND METHODS: A total of 71 examples of artificial tear preparations were identified in a search of Vademecum 2014 and the Spanish Medicines Agency website. In the 24 artificial tear products containing phosphates, quantification of these was performed by ultraviolet molecular absorption spectrophotometry, and the determination of pH was performed using scan image analysis algorithms of pH strips. RESULTS: Of the 71 artificial tears tested, 24 contained phosphate among their excipients in the data sheet, three of which had a concentration level below detection limit (<0.1mM). The mean phosphate concentration was 17.91±23.87mM. The artificial tear sample containing a higher concentration was Colircusi Humectante (87.1mM). Lubricants based on hypromellose showed the highest phosphate concentration (41.59±32.1mM), showing statistically significant differences compared to povidone (P=.0196) and hyaluronate (P=.0067). Statistically significant differences were found between products containing preservatives (32.39±20.91mM), and preservative free ones (8.49±11.98mM) (P=.0498). However, no difference was found between multidose (20.21±26.91mM) and unidose (9.31±14.39mM) samples, or between brand name (15.44±23.3mM) and generic eye drops (20.81mM). The mean pH was 6.93±0.26 (6.2-7.22). No statistical correlation was detected between phosphate concentration and pH (Spearman's Rho -0.1089 and P=.6125). CONCLUSION: A total of 24 (33.8%) of the 71 artificial tears contained phosphate. We believe identifying the phosphate concentration of artificial tears is useful information in order to avoid complications in high-risk patients.

Pullulan: an advantageous natural polysaccharide excipient to formulate tablets of alendronate-loaded microparticles

This work reports the preparation of tablets by direct compression of sodium alendronate-loaded microparticles, using pullulan as filler. The tableting properties of pullulan were compared with those of microcrystalline cellulose and lactose. Pullulan tablets showed low variations in average weight, thickness and drug content. Moreover, these tablets exhibited a higher hardness compared to the other excipients. In vitro release studies showed that only pullulan was capable to maintain gastroresistance and release properties of microparticles, due to its ability to protect particles against damage caused by compression force. Thus, pullulan was considered an advantageous excipient to prepare tableted microparticles.

Neste trabalho relata-se a preparação de comprimidos pela compressão direta de micropartículas contendo alendronato de sódio, utilizando o pullulan como diluente. As propriedades dos comprimidos de pullulan foram comparadas com as de comprimidos de celulose microcristalina e de lactose. Os comprimidos de pullulan mostraram baixa variação no peso médio, espessura e teor. Por outro lado, estes apresentaram altos valores de dureza comparados aos preparados com os outros excipientes. Através dos estudos de liberação in vitro pode-se observar que apenas o pullulan foi capaz de manter a gastrorresistência e as propriedades de liberação das micropartículas, o que se deve à sua capacidade de proteger as partículas do dano causado pela força de compressão. Dessa forma, o pullulan foi considerado um excipiente vantajoso para a preparação de comprimidos microparticulados.

Contrasting the crospovidones functionality as excipients for direct compression

Specific values of technological properties of excipients allow the establishment of numerical parameters to define and compare their functionality. This study investigates the functionality of Polyplasdones XL and XL10. Parameters studied included tablet disintegration profiles, compactibility profiles and powder flow. The results allowed the establishment of quantitative surrogate functionalities of technological performance, such as absolute number, and as a value relative to the known microcrystalline cellulose type 102. Moreover, the establishment of an explicit functionality to improve the technological performance of two diluents and a model drug was investigated, as was setting up of these functionalities, as quantitative values, to determine the input variables of each material and its probable functionality in a drug product. Disintegration times of pure Polyplasdone XL and its admixtures were around half that of Polyplasdone XL10. The improvement in tablet compactibility was 25-50% greater for Polyplasdone XL10 than Polyplasdone XL. Crospovidones proportions of up to 10% have little effect on the flow properties of other powders, although pure Polyplasdone XL10 and its admixtures display compressibility indexes about 20% greater than Polyplasdone XL. The observed results are in line with a smaller particle size of Polyplasdone XL10 compared to Polyplasdone XL.

Os valores específicos de propriedades tecnológicas de excipientes permitem o estabelecimento de parâmetros numéricos para definir e comparar a sua funcionalidade. Este estudo investiga a funcionalidade dos excipientes. Os parâmetros estudados foram perfis de desintegração dos comprimidos, perfis de compactação e fluxo de pó. Os resultados permitiram expressar o desempenho tecnológico através de valores absolutos e valores relativos à conhecida celulose microcristalina tipo 102. Do mesmo modo, permitiram estabelecer uma funcionalidade explícita para melhorar o desempenho tecnológico de dois diluentes e um fármaco modelo. A criação destas funcionalidades, como valores quantitativos, permite conhecer as variáveis de entrada de cada material e sua provável funcionalidade em um medicamento. Os tempos de desintegração do Poliplasdone XL e das suas misturas são cerca da metade do observado para as misturas com o Poliplasdone XL10. Melhoria da compressão de comprimidos que contêm Polyplasdone XL10 é 25-50% maior do que o Polyplasdone XL. Crospovidonas em proporções de até 10% têm pouco efeito sobre as propriedades de fluxo dos outros pós embora o Poliplasdone XL10 e suas misturas exibam índices de compressibilidade cerca de 20% maior do que o Poliplasdone XL. Os resultados observados estão em sintonia com o menor tamanho de partícula do Poliplasdone XL10, em comparação com o Poliplasdone XL.

In vivo mucoadhesive strength appraisal of gum Manilkara zapota

The mucilage (MMZ) extracted from the seeds of Manilkara zapota(Linn.) P. Royen syn. using maceration techniques was evaluated for mucoadhesive strength by various in vitro and in vivo methods. The result showed that mucoadhesive strength of seeds mucilage have comparable property toward natural and synthetic polymers such as Guar Gum and hydroxyl propyl methyl cellulose (HPMC E5LV) under the experimental conditions used in this study. Briefly, it could be concluded that the seed mucilage of Manilkara zapota can be used as a pharmaceutical excipient in oral mucoadhesive drug delivery systems. Further, it may be appropriate to study the changes in these properties after chemical modifications.

Mucilagem (MMZ) extraída das sementes de Manilkara zapota(Linn.) P. Royen syn utilizando técnicas de maceração foi avaliada por sua força mucoadesiva por vários métodos in vitro e in vivo. O resultado mostrou que a força mucoadesiva das sementes mucilaginosas tem propriedade comparável aos polímeros naturais e sintéticos, tais como goma Guar e hidroxipropilmetil celulose (HPMC E5LV) nas condições experimentais utilizadas neste estudo. Brevemente, se pode concluir que a mucilagem de semente de Manilkara zapota pode ser usada como um excipiente farmacêutico em sistemas de liberação de fármacos mucoadesivos por via oral. Pode ser apropriado o estudo posterior de mudanças nessas propriedades após modificações químicas.

Effects of polyethylene glycols on intestinal efflux pump expression and activity in Caco-2 cells

The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.

O presente estudo foi planejado para investigar a influência de polietileno glicóis sobre a atividade e expressão da P- glicoproteína (P-gp) . Concentrações sub-tóxicas de PGPs e em células Caco-2 foram determinadas por meio do ensaio de MTT. Em seguida, efetuou-se a a medida de captura de Rodamina-123 (Rho-123), um substrato fluorescente de P-gp, em células Caco-2, confrontando com PEG 400 (1% e 2% m/v), PEG 4000 (2% e 4% m/v) e PEG 6000 (2% e 4% m /v), PEG 10000 (2% e 4% w/v), PEG 15000 (1% e 2% m/v), e PEG 35000 (2% e 4% m/v). Essa medida foi efetuada durante a noite, para saber se as concentrações não tóxicas de excipientes são capazes de influenciar a actividade da P-gp. Além disso, realizou-se o western blotting para investigar a expressão da proteína P-gp. Os resultados mostraram que o PEG 400, nas concentrações de 1% (m/v) e 2% (m/v), e PEG 6000, na concentração de 4% (m/v) são capazes de bloquear P-gp. Com base nos resultados conclui-se que os excipientes mencionados poderiam ser utilizados para obstruir o efluxo por P-gp, a fim de aumentar a biodisponibilidade de do fármaco co-administrado.