Optimization of the Cohesion Index in the SeDeM Diagram Expert System and application of SeDeM Diagram: An improved methodology to determine the Cohesion Index.

In this study, we suggest optimizing the methodology to determine the Cohesion Index (Icd) in order to avoid mistaken characterizations due to powder bulk density. For this purpose, five different excipients, with different bulk densities and of different chemical nature, were compressed at different heights. Their compression and their tablet characterization enable establishing a powder weight for compression in accordance with its bulk density. Therefore, the resulting tablet will have a height within a defined range of heights where it has no critical effects on its hardness. Then, the impact of this optimization is shown in a formula development, one of the main SeDeM's applications. A mathematical equation was used to calculate the theoretical amount of excipient to formulate the API according to both methodologies. The compression results demonstrate that the characterization with the NM-Icd is more accurate than the previous one while preserving its simplicity.

Osmolality predictive models of different polymers as tools in parenteral and ophthalmic formulation development.

During the development of parenteral dosage forms, different physicochemical studies are required to ensure stable, effective and safe formulations. The osmolality of this kind of dosage forms should bear a close similarity to the body fluids to prevent local irritation, pain or even more significant side effects like endothelial damage. The osmotic studies performed in Polyethylene glycol 400 (PEG 400), Polyethylene glycol 4000 (PEG 4000), Poloxamer 407 (P407), Sodium Hyaluronate (SH), Chondroitin Sulphate Sodium (CS), Cremophor RH 40 (CRE40) and Polyvinyl alcohol (PVA) aqueous solutions, showed that the theoretical determination of the osmolality based on their molecular weight as the only determinant factor did not agree with the values obtained by the measurement of colligative properties such as the freezing point depression. The data obtained from this study and its analysis, provided predictive equations that can be used as tools in the primary development to estimate formulation's osmolality at different concentrations; and its evolution over a period at the hypothetical worst-case scenario of storage temperature.

[Lipid emulsion selection in parenteral nutrition. Biochemical and hematological paramaters]. / Selección de emulsiones lipídicas en nutrición parenteral: parámetros bioquímicos y hematológicos.

INTRODUCTION: Lipid emulsions (LE) are a component of parenteral nutrition (PN) and its fatty acid (FA) profile determines various physiological responses. OBJECTIVES: To assess the adequacy of a clinical not restricted protocol in the choice of LE by studying complementary biochemical and hematological parameters (BHP) at the beginning of the PN. METHODS: A 4-year retrospective observational study of LE administered to patients with PN. Demographic, clinical, nutritional and analytical variables at the beginning of the PN were collected. Univariate and multivariate analyses were performed to study the correlation between the initial clinical and biochemical parameters and the LE profile used. RESULTS: Four hundred and sixty patients (29.5%) out of 1,558 had BHP at the beginning of PN and used mainly the LE combinations soybean (SO) + medium-chain triglycerides (MCT) + olive (OO) + fish (FO) (37.4%) and SO + MCT + OO (35.6%). Statistically significant differences on the LE pattern were observed between patients with and those without initial BHP (44.8% vs39.5% received FO, respectively). Conditions regularly associated with elevated C-reactive protein (CRP) were associated with increased use of FO LE: SO+OO+FO (OR: 4.52 [95% CI: 1.43-13.91]) and SO+MCT+OO+FO (OR: 3.34 [95% CI: 2.10-5.33]). In those complex conditions related with the critical patient MCT were used: hepatic failure (SO+MCT OR: 2.42 [95% CI: 1.03-5.68]) and renal failure (SO+MCT+FO OR: 3.34 [95% CI: 1.12-9.99]). CONCLUSIONS: The use of BHP at the beginning of PN treatment allows complementing the clinical and metabolic criteria in LE selection.

INTRODUCCIÓN: el patrón de ácidos grasos (AG) de las emulsiones lipídicas (EL) utilizadas en nutrición parenteral (NP) condiciona diferentes respuestas fisiológicas. OBJETIVOS: estudiar si los criterios clínicos de prescripción de EL en NP establecidos en nuestro protocolo abierto y basados en recomendaciones se correlacionan con marcadores bioquímicos y hematológicos iniciales. MÉTODOS: estudio observacional retrospectivo de cuatro años. Se recogieron variables demográficas, clínicas, nutricionales y analíticas al inicio de la NP. Se realizó un análisis uni y multivariante para estudiar la asociación entre los valores iniciales de los parámetros bioquímicos y hematológicos (PBHE) y el tipo de emulsión lipídica empleada. RESULTADOS: de los 1.558 pacientes, 460 pacientes (29,5%) tenían PBHE al inicio de la NP y utilizaron mayoritariamente las combinaciones soja (AS) + triglicéridos de cadena media (MCT) + oliva (AO) + pescado (AP) (37,4%) y AS+MCT+AO (35,6%). Se encontraron diferencias estadísticamente signifiativas en el patrón EL utilizado entre los pacientes con y sin PBHE: patrón de AG con AP 44,8% vs.39,5%, respectivamente. Las situaciones clínicas con proteína C-reactiva (PCR) elevada se asociaron con mayor uso de EL con AP: AS+AO+AP (OR: 4,52 [IC 95%: 1,43-13,91] y AS+MCT+AO+AP (OR: 3,34 [IC 95%: 2,10-5,33]). En situaciones clínicas complejas asociadas con paciente crítico se utilizó EL con MCT: afectación hepática (AS+MCT OR: 2,42 [IC 95%: 1,03-5,68]) y afectación renal (AS+MCT+AP OR: 3,34 [IC 95%: 1,12-9,99]). CONCLUSIONES: la inclusión protocolizada de PBHE al inicio de la NP permite complementar criterios clínicos y metabólicos en la elección de la EL.

Selección de emulsiones lipídicas en nutrición parenteral: parámetros bioquímicos y hematológicos / Lipid emulsion selection in parenteral nutrition. Biochemical and hematological paramaters

Introducción: el patrón de ácidos grasos (AG) de las emulsiones lipídicas (EL) utilizadas en nutrición parenteral (NP) condiciona diferentes respuestas fisiológicas. Objetivos: estudiar si los criterios clínicos de prescripción de EL en NP establecidos en nuestro protocolo abierto y basados en recomendaciones se correlacionan con marcadores bioquímicos y hematológicos iniciales. Métodos: estudio observacional retrospectivo de cuatro años. Se recogieron variables demográficas, clínicas, nutricionales y analíticas al inicio de la NP. Se realizó un análisis uni y multivariante para estudiar la asociación entre los valores iniciales de los parámetros bioquímicos y hematológicos (PBHE) y el tipo de emulsión lipídica empleada. Resultados: de los 1.558 pacientes, 460 pacientes (29,5%) tenían PBHE al inicio de la NP y utilizaron mayoritariamente las combinaciones soja (AS) + triglicéridos de cadena media (MCT) + oliva (AO) + pescado (AP) (37,4%) y AS+MCT+AO (35,6%). Se encontraron diferencias estadísticamente significativas en el patrón EL utilizado entre los pacientes con y sin PBHE: patrón de AG con AP 44,8% vs. 39,5%, respectivamente. Las situaciones clínicas con proteína C-reactiva (PCR) elevada se asociaron con mayor uso de EL con AP: AS+AO+AP (OR: 4,52 [IC 95%: 1,43-13,91] y AS+MCT+AO+AP (OR: 3,34 [IC 95%: 2,10-5,33]). En situaciones clínicas complejas asociadas con paciente crítico se utilizó EL con MCT: afectación hepática (AS+MCT OR: 2,42 [IC 95%: 1,03-5,68]) y afectación renal (AS+MCT+AP OR: 3,34 [IC 95%: 1,12-9,99]). Conclusiones: la inclusión protocolizada de PBHE al inicio de la NP permite complementar criterios clínicos y metabólicos en la elección de la EL (AU)

Introduction: Lipid emulsions (LE) are a component of parenteral nutrition (PN) and its fatty acid (FA) profile determines various physiological responses. Objectives: To assess the adequacy of a clinical not restricted protocol in the choice of LE by studying complementary biochemical and hematological parameters (BHP) at the beginning of the PN. Methods: A 4-year retrospective observational study of LE administered to patients with PN. Demographic, clinical, nutritional and analytical variables at the beginning of the PN were collected. Univariate and multivariate analyses were performed to study the correlation between the initial clinical and biochemical parameters and the LE profile used. Results: Four hundred and sixty patients (29.5%) out of 1,558 had BHP at the beginning of PN and used mainly the LE combinations soybean (SO) + medium-chain triglycerides (MCT) + olive (OO) + fi sh (FO) (37.4%) and SO + MCT + OO (35.6%). Statistically significant differences on the LE pattern were observed between patients with and those without initial BHP (44.8% vs 39.5% received FO, respectively). Conditions regularly associated with elevated C-reactive protein (CRP) were associated with increased use of FO LE: SO+OO+FO (OR: 4.52 [95% CI: 1.43-13.91]) and SO+MCT+OO+FO (OR: 3.34 [95% CI: 2.10-5.33]). In those complex conditions related with the critical patient MCT were used: hepatic failure (SO+MCT OR: 2.42 [95% CI: 1.03-5.68]) and renal failure (SO+MCT+FO OR: 3.34 [95% CI: 1.12-9.99]). Conclusions: The use of BHP at the beginning of PN treatment allows complementing the clinical and metabolic criteria in LE selection (AU)

Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant.

Establishment of criteria for the selection and adaptation of objectives and indicators in ISO9001: 2008 quality system in a university pharmaceutical pilot plant / Establecimiento de criterios para la selección y adaptación de objetivos e indicadores en un sistema de calidad ISO9001:2008 en una planta piloto farmacéutica universitaria

Aims: The aim of this work is the correct establishment and follow-up of quality objectives and indicators as the cornerstones of a quality assurance system, in this case focused on ISO9001. Materials and methods: In this work, the authors present the criteria that, in their view, an organization must follow for a better selection and adaptation of the ISO9001:2008 quality system objectives and indicators applied to a university pharmaceutical pilot plant. The evolution of errors in setting objectives and indicators is assessed. Results: Based on the experience of several years at the SDM (Service of Development of Medicines) at the Faculty of Pharmacy of the University of Barcelona, the results show that the establishing of appropriate objectives and indicators is not an easy task. A careful selection of both objectives and indicators must be a compulsory step prior to the establishment of a robust, reliable quality assurance system through years. Conclusions: Experience over time proves to be a powerful tool to end up selecting the right quality objectives and indicators for such quality system. Since this task is not always easy to carry out, is necessary to set a selection of criteria in order to obtain useful information that contributes to the continuous improvement of the quality system

Objetivos: El objetivo de este trabajo es el correcto establecimiento y seguimiento de los objetivos de calidad y sus indicadores, como pilar fundamental de un sistema de garantía de calidad, en este caso centrado en ISO9001. Material y métodos: En este trabajo, los autores presentan los criterios que, a su juicio, una organización debe seguir para una mejor selección y adaptación de objetivos e indicadores en el marco de la norma de calidad ISO9001:2008, aplicada a una planta piloto farmacéutica universitaria. Se realiza una evaluación de los errores en el establecimiento de objetivos e indicadores. Resultados: En base a la experiencia de varios años en SDM (Servicio de Desarrollo del Medicamento) en la Facultad de Farmacia de la Universidad de Barcelona, los resultados muestran que el establecimiento de objetivos e indicadores apropiados no resulta una tarea sencilla. Una cuidadosa selección tanto de objetivos como de indicadores debe ser un paso obligado para el establecimiento de un sistema de aseguramiento de calidad robusto y fiable a lo largo del tiempo. Conclusiones: El aprendizaje basado en la experiencia de años demuestra ser una herramienta poderosa para acabar seleccionando los objetivos e indicadores correctos que se adapten al sistema de calidad en cuestión. Dado que este hecho no siempre resulta fácil, es necesario establecer unos criterios con el objetivo de obtener información útil que contribuya a la mejora continua del sistema de calidad (AU)