Optimisation of the Manufacturing Process of Organic-Solvent-Free Omeprazole Enteric Pellets for the Paediatric Population: Full Factorial Design.

Liquid formulations are mostly used in the paediatric population. However, with certain active pharmaceutical ingredients (APIs), it is very difficult to guarantee quality and stability; this is the case, for example, with omeprazole. Omeprazole is used as a model drug due to the lack of a paediatric formulation meeting gastro-resistance requirements, which remains a challenge today. In this experimental study, the development of enteric polymer-coated pellets is proposed. It is proposed to use aqueous coating dispersions without the use of organic solvents, which are commonly used in fluidised bed coatings. To do this, the design of experiments method is used as a statistical tool for experiment creation and the subsequent analysis of the responses. In particular, this study uses a randomised full factorial design. The mean weight increases of the protective layer and the enteric coating are chosen as factors. Each factor is assigned two levels. Therefore, the design of the used experiments is a 22 + 1 central point. Overall, the obtained pellets can be an alternative to the compounding formulas of omeprazole that are currently used in the paediatric population, which do not meet the gastro-resistance specifications necessary to guarantee the therapeutic efficacy of this active ingredient.

New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.

Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.

Excipients in the Paediatric Population: A Review.

This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied.

Spatiotemporal Analysis of Hydration Mechanism in Sodium Alginate Matrix Tablets.

Methods of spatiotemporal characterization of nonequilibrated polymer based matrices are still immature and imperfect. The purpose of the study was to develop the methodology for the spatiotemporal characterization of water transport and properties in alginate tablets under hydration. The regions of low water content were spatially and temporally sampled using Karl Fisher and Differential Scanning Callorimetry (spatial distribution of freezing/nonfreezing water) with spatial resolution of 1 mm. In the regions of high water content, where sampling was infeasible due to gel/sol consistency, magnetic resonance imaging (MRI) enabled characterization with an order of magnitude higher spatial resolution. The minimally hydrated layer (MHL), infiltration layer (IL) and fully hydrated layer (FHL) were identified in the unilaterally hydrated matrices. The MHL gained water from the first hour of incubation (5-10% w/w) and at 4 h total water content was 29-39% with nonfreezing pool of 28-29%. The water content in the IL was 45-47% and at 4 h it reached ~50% with the nonfreezing pool of 28% and T2 relaxation time < 10 ms. The FHL consisted of gel and sol layer with water content of 85-86% with a nonfreezing pool of 11% at 4 h and T2 in the range 20-200 ms. Hybrid destructive/nondestructive analysis of alginate matrices under hydration was proposed. It allowed assessing the temporal changes of water distribution, its mobility and interaction with matrices in identified layers.

Cross-sectional study on medicinal products without commercial interest (MPWCI) in the Spanish market.

OBJECTIVE: To confirm that there is a defined group of products to be protected in the Spanish therapeutic arsenal known as 'medicinal products without commercial interest' (MPWCI) and propose the adoption of legal measures aimed at avoiding, or reducing, the lack of supply of said products. DESIGN: A cross-sectional study of proposed MPWCI based on a survey. The Spanish Agency of Medicines and Medical Devices (AEMPS) was asked for a list of presentations of medicines in order to identify those whose lack could have an impact on welfare. SETTING: A search on the AEMPS website and a survey conducted among 44 companies belonging to Farmaindustria has allowed for the development of a proposal list of presentations that should continue to be marketed in Spain. RESULTS: Products proposed as MPWCI are old (50% of them have an authorisation of more than 50 years) and are developed by active substances of chemical origin, parenterally administered much more frequently than the rest of the general market (44%vs6.6%, respectively). Unlike oral forms, injectable forms require adequate manufacturing facilities to guarantee the quality and sterility of the product, which naturally increases the cost of the product whose price is low or obsolete. The company experts have not valued the current price revisions as a sufficient enough mechanism to change the consideration of these medicines with respect to the interest on the part of some Marketing Authorisation Holders to maintain their commercialisation. CONCLUSIONS: As shown in the results, an upward revision of prices is necessary to contribute to the permanence of these presentations in the market, although some experts do not consider the current price revisions satisfactory enough to maintain these presentations in the market. Therefore, a specific regulation seems necessary to ensure the continuity on the market of these proposed products.

Topical Administration of Bosentan Prevents Retinal Neurodegeneration in Experimental Diabetes.

Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice. For this purpose, db/db mice aged 10 weeks were treated with one drop of bosentan (5 mg/mL, n = 6) or vehicle (n = 6) administered twice daily for 14 days. Six non-diabetic (db/+) mice matched by age were included as the control group. Glial activation was evaluated by immunofluorescence using specific antibodies against glial fibrillary acidic protein (GFAP). Apoptosis was assessed by TUNEL method. A pharmacokinetic study was performed in rabbits. We found that topical administration of bosentan resulted in a significant decrease of reactive gliosis and apoptosis. The results of the pharmacokinetic study suggested that bosentan reached the retina through the trans-scleral route. We conclude that topical administration of bosentan was effective in preventing neurodegeneration in the diabetic retina and, therefore, could be a good candidate to be tested in clinical trials.

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.

A new design for the review and appraisal of semi-solid dosage forms: Semi-solid Control Diagram (SSCD).

The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of different excipients and different semi-solid dosage forms. It can be used to review and evaluate different formulations and/or batches and facilitate the selection of one of them that will present the most suitable galenic characteristics for topical application. It is also useful to track stability studies by comparing the diagrams, which allows to measure the impact of subjecting the formulation to different conditions and times to be examined. In this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for studying and evaluating semi-solid pharmaceutical dosage forms, by comparing several different semisolid preparations (lipogels). With these results, the tool is validated and the best formulation has been discriminated from the others.

Comparison of the Cockcroft-Gault, MDRD and CKD-EPI equations for estimating ganciclovir clearance.

AIMS: Accurately estimating kidney function is essential for the safe administration of renally cleared drugs such as ganciclovir. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault equation. There are no data on the utility of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in ganciclovir dosing. To evaluate which renal function equation best predicts ganciclovir clearance. METHODS: The performance of the Cockcroft-Gault equation, isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD study (MDRD4-IDMS) equation and CKD-EPI equation in determining ganciclovir clearance were assessed retrospectively in patients treated with ganciclovir from 2004-2015. The MDRD4-IDMS and CKD-EPI equations adjusted to individual body surface area (MDRD4-IDMS·BSA and CKD-EPI·BSA, respectively) were also evaluated. Patients with intravenous ganciclovir peak and trough concentrations in their medical records were included in the study. Ganciclovir clearance was calculated from serum concentrations using a one-compartment model. The five equations were compared based on their predictive ability, the coefficient of determination, through a linear regression analysis. The results were validated in a group of patients. RESULTS: One hundred patients were included in the final analysis. Seventy-four patients were analysed in the learning group and 26 in the validation group. The coefficient of determination was 0.281 for Cockcroft-Gault, 0.301 for CKD-EPI·BSA, 0.308 for MDRD4-IDMS·BSA, 0.324 for MDRD4-IDMS and 0.360 for CKD-EPI. Subgroup analysis also showed that CKD-EPI is a better predictor of ganciclovir clearance. Analysis of the validation group confirmed these results. CONCLUSIONS: The CKD-EPI equation correlates better with ganciclovir clearance than the Cockcroft-Gault and MDRD4-IDMS equations, even the clinical difference between the equations is scarce.

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.

The role of SeDeM for characterizing the active substance and polyvinyilpyrrolidone eliminating metastable forms in an oral lyophilizate-A preformulation study.

A preformulation study of an oral lyophilisate with cetirizine dihydrochloride (CTZ) as active ingredient, mannitol and PVP K30 as bulking agents is presented. CTZ shown a humidity content of 0.150% and a spontaneous hygroscopicity of 0.200% (both determined by SeDeM diagram), demonstrating an adequate stability behavior in solid form. A design of experiments (DoE) performed with both mannitol and PVP K30, followed by a simple factorial design (32) has determined the optimum combination of excipients and CTZ, and showed that a higher proportion of PVP K30 was able to prevent metastable forms generated by mannitol.

[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)

Effectiveness of Cinacalcet in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Not Receiving Dialysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease (CKD) patients. Cinacalcet could be a therapeutic option although its use is controversial in patients not receiving dialysis. Thus, the aim of this study is to assess the effectiveness and safety of cinacalcet in patients with CKD and SHPT without renal replacement treatment (RRT) and without renal transplantation (RT). METHODS: A retrospective observational study was conducted. Patients were included if they had collected cinacalcet, under off-label use, during 2010 and 2011. Patients selected were followed from the beginning of cinacalcet therapy for one year of treatment. RESULTS: A total of 37 patients were included with CKD stage 3 (38%), 4 (51%) and 5 (11%). Baseline mean PTH value was 400.86 ± 168.60 mg/dl. At 12 months, a 67% of patients achieved at least a 30% reduction in their PTH value (p<0.001; CI 49.7-83.6), and the overall mean reduction of PTH values was 38% (p< 0.001; IC -49.1, -27.5). A 28% of the patients achieved KDOQI PTH goals (p = 0.003, CI 12%-50%). At 12 months, mean serum calcium values decreased by 6% and mean serum phosphorus values increased by 13%. A 19% of patients experienced hypocalcemia episodes while an increase of 24% in hyperphosphatemia episodes was observed. A 25% of patients finished cinacalcet before a year of treatment. Main withdrawal reasons were: gastrointestinal and other discomfort (8%), hypocalcaemia (8%), non-compliance (3%), interactions (3%) and excess of efficacy (3%). CONCLUSIONS: Cinacalcet was effective in patients with CKD and SHPT not receiving dialysis. Electrolytic imbalances could be managed with administration of vitamin D and analogues or phosphate binders.

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.

Approach to design space from retrospective quality data.

CONTEXT: Nowadays, the entire manufacturing process is based on the current GMPs, which emphasize the reproducibility of the process, and companies have a lot of recorded data about their processes. OBJECTIVE: The establishment of the design space (DS) from retrospective data for a wet compression process. MATERIALS AND METHODS: A design of experiments (DoE) with historical data from 4 years of industrial production has been carried out using the experimental factors as the results of the previous risk analysis and eight key parameters (quality specifications) that encompassed process and quality control data. RESULTS: Software Statgraphics 5.0 was applied, and data were processed to obtain eight DS as well as their safe and working ranges. DISCUSSION AND CONCLUSION: Experience shows that it is possible to determine DS retrospectively, being the greatest difficulty in handling and processing of high amounts of data; however, the practicality of this study is very interesting as it let have the DS with minimal investment in experiments since actual production batch data are processed statistically.

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)

Application of a validated method in the stability study of colistin sulfate and methylparaben in a veterinary suspension formulation by high-performance liquid chromatography with a diode array detector.

A methodology following International Cooperation on Harmonization for Veterinary Products (VICH) guidelines for the stability evaluation of colistin sulfate in a nonaqueous suspension pharmaceutical dosage form for veterinary use (via their drinking water) is described. This method monitors the percentage of colistin sulfate during the stability study of the preparation in drinking water and establishes the shelf life of the final product by a new high-performance liquid chromatography method which was developed and validated for the simultaneous determination of colistin sulfate [colistin A (Polymixin E1) and colistin B (Polymixin E2)] and methylparaben (Nipagin) using a diode array detector (DAD). The method uses a Kromasil C18 column and isocratic elution. The mobile phase consisted of an acetonitrile-sodium sulfate anhydrous solution (25 + 75) pumped at a flow rate of 1.5 mL/min. The DAD was set at 215 nm. The validation study was carried out according to the VICH guidelines in order to prove that the new analytical method meets the reliability characteristics, which include the fundamental criteria for validation: selectivity, linearity, precision, accuracy, and sensitivity. The method was applied during the quality control or stability studies of the suspension dosage form in order to quantify the drug (colistin) and preservative, and proved to be suitable for rapid and reliable quality control.