Conciliación farmacoterapéutica al ingreso hospitalario en el Servicio de Guardia de Adultos / Medication reconciliation at hospital admission in an Adults Guard Service

Objetivo: Detectar los errores de conciliación terapéutica (EC) en pacientes adultos que asisten al Servicio de Guardia de Adultos (SGA) de una institución privada de tercer nivel de atención, describir su medicación de base y determinar la gravedad potencial de las discrepancias encontradas.Métodos: Se realizó un estudio observacional, descriptivo y prospectivo. Se relevó la medicación de pacientes mayores de 18 años ingresados al SGA, mediante anamnesis directa e indirecta. Posteriormente se comparó con las nuevas prescripciones a fin de detectar las posibles discrepancias. Los tipos de discrepancia y su gravedad potencial fueron clasificadas según la Nacional Coordinating Council for Medication Error Reporting and Prevention (NCCMERP).Resultados: Se conciliaron 100 pacientes, de los cuales el 71% presentó EC, con una media de 1,8 EC/paciente. El número total de medicamentos conciliados fue de 682, detectándose 324 discrepancias totales, 198 justificadas y 126 que requieren aclaración, consideradas EC. La mayoría de los EC fueron por omisión de medicamentos. Se identificaron 21 interacciones farmacológicas, siendo 12 clínicamente relevantes. La aceptación de las intervenciones por los médicos tratantes fue del 62%. La gravedad de los EC encontrados pudo incluirse en las categorías A-D.Conclusiones: La conciliación terapéutica realizada por el farmacéutico en el SGA evitó potenciales errores de medicación clínicamente relevantes y pone en evidencia la falta de exhaustividad en la recopilación de información sobre medicación domiciliaria del paciente. (AU)

Objective: To detect medication reconciliation errors (MRE) in adult patients attending the Adults Guard Service of a private third-level hospital; describe their basic medication and determine the potential severity of the discrepancies found.Methods: An observational, descriptive and prospective study was carried out. The medication of patients older than 18 years admitted in the adults guard service was relieved, through direct and indirect anamnesis. Subsequently, it was compared with the new prescriptions in order to detect possible discrepancies. The types of discrepancies and their potential severity were classified according to the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP).Results: 100 patients were reconciled, of which 71% presented MRE, with a mean of 1.8 MRE/patient. The total number of reconciled medications was 682, detecting 324 total discrepancies, 198 justified and 126 requiring clarification, which were considered reconciliation errors. Most of the MRE were due to medication omissions. In addition, 21 pharmacological interactions were identified, being 12 clinically relevant. Acceptance of interventions by treating physicians was 62%. The severity of the MRE could be included in categories A-D.Conclusions: The intervention of the pharmacist avoided potential MRE and highlights the lack of exhaustiveness in collecting information of the patient’s home medication. (AU)

Monitorización de concentraciones plasmáticas de vancomicina en pacientes críticos de un hospital público de Córdoba, Argentina / Monitoring of plasma vancomycin concentrations in critically ill patients in a public hospital of Córdoba, Argentina

Introducción: La monitorización de las concentraciones plasmáticas de antimicrobianos utilizados para tratar infecciones en pacientes críticos es una de las estrategias propuestas para mejorar los resultados clínicos. La monitorización de vancomicina reduce el riesgo de resistencia bacteriana y de nefrotoxicidad relacionada con altas concentraciones plasmáticas. El estudio fue realizado en un hospital público de la provincia de Córdoba, Argentina, que contiene 43 unidades críticas de atención al paciente. Aunque la indicación de vancomicina es frecuente, la solicitud de niveles plasmáticos de fármacos es inusualMétodo: El Servicio de Farmacia realizó un estudio piloto prospectivo durante 14 semanas, implementando el monitoreo de las concentraciones plasmáticas de vancomicina y el cálculo del índice ABC24/CIM (área bajo la curva de concentración-tiempo durante un período de 24 horas/concentración inhibitoria mínima).Objetivos: Determinar el porcentaje de pacientes con concentraciones plasmáticas valle fuera del rango terapéutico descrito en la literatura y la dosis que sería necesaria para obtener un ABC24/CIM ≥400.Resultados: Se realizaron 36 solicitudes de monitorización de vancomicina en 31 pacientes. El 78% de las concentraciones plasmáticas determinadas estaban fuera del rango terapéutico y sólo en 8 pacientes se obtuvo un ABC24/CIM ≥400.Conclusiones: Este estudio fue el primer paso para implementar la farmacocinética clínica en la institución y evidenció la importancia de la monitorización terapéutica y la individualización de la dosis. En pacientes críticos y con un aclaramiento de creatinina elevado se necesitarían dosis mayores a las utilizadas en este estudio. (AU)

Introduction: Monitoring plasma concentrations of antimicrobials used to treat infections in critically ill patients is one of the strategies proposed to improve clinical results. Vancomycin monitoring reduces the risk of bacterial resistance and nephrotoxicity related to high plasma concentrations. The study was carried out in a public hospital in the province of Córdoba, Argentina, which contains 43 critical patient care units. Although the indication for vancomycin is frequent, the request for plasma levels of drugs is unusual.Method: The Pharmacy Service carried out a prospective pilot study for 14 weeks, implementing the monitoring of plasma vancomycin concentrations and the calculation of the ABC24/MIC index (area under the concentration-time curve over a 24-hour period/inhibitory concentration minimum).Objectives: To determine the percentage of patients with trough plasma concentrations outside the therapeutic range described in the literature and the dose that would be necessary to obtain an ABC24/CIM ≥400.Results: 36 requests for vancomycin monitoring were made in 31 patients. 78% of the determined plasma concentrations were outside the therapeutic range and only in 8 patients was an ABC24/CIM ≥400 obtained.Conclusions: This study was the first step to implement clinical pharmacokinetics in the institution and showed the importance of therapeutic monitoring and dose individualization. In critically ill patients with high creatinine clearance, higher doses than those used in this study would be required. (AU)

The role of hyaluronan as a drug carrier to enhance the bioavailability of extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a model case.

The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance.

Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies.

Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.

Hyaluronan as drug carrier. The in vitro efficacy and selectivity of Hyaluronan-Doxorubicin complexes to affect the viability of overexpressing CD44 receptor cells.

We report Doxorubicin ionic complexes with hyaluronic acid (HiH-Dx) or its sodium salt (HiNa-Dx) as tumor-targeting delivery system. The complexes were prepared in situ by mixing aqueous solutions of Dx.HCl with HiH or HiNa. Clear colloidal dispersions with a high degree of counterionic condensation (cc) were obtained. Affinity constants (logKcc) of HiNa-Dx and HiH-Dx were 7.96 and 8.08, respectively. Delivery rates of Dx from the complexes were measured in a Franz-type bicompartimental device. In line with the high affinity constants, loaded Dx was slowly released from the complexes. To test the targeting potential of the complexes, carcinogenic A549 cells overexpressing the CD44 receptors were used. HTR8/SVneo cells without overexpression of CD44 were used as control. In A549 cells, cytotoxicity of both HiH-Dx and HiNa-Dx complexes was 3-fold higher than that of the reference solution. However, no differences were observed between the complexes and free Dx solution in HTR8/SVneo cells. Flow cytometry data suggested successful uptake of Dx in cells, with a greater internalization of Dx in A549 cells than in HTR8/SVneo cells when the complexes were used. Similarly, microscopy imagines revealed a higher concentration of Dx in A549 cells with the complexes. This work provides more detailed information in order to contribute to more solid bases to evaluate the potentiality of Hi as an antineoplastic drug carrier convenient for being used in specific therapeutic indications with minimal side effects.

Stability evaluation of 7 % chloral hydrate syrup contained in mono and multi-dose bottles under room and refrigeration conditions.

PURPOSE: To evaluate the stability of an extemporaneously prepared 7% chloral hydrate syrup under different conditions of storage and dispensing. METHODS: Three batches of 7% chloral hydrate syrup were prepared. Each batch was stored in 50 light-resistant glass containers of 60 mL with child-resistant caps and in two bottles of 1000 mL to simulate two forms of dispensing, mono and multi-dose, respectively. Twenty five mono-dose bottles and a multi-dose bottle of each batch were stored under room conditions (20 ± 1 °C) and the rest of the samples were stored in the fridge (5 ± 2 °C). The physical, chemical and microbiological stability was evaluated for 180 days. Stability was defined as retention of at least 95% of the initial concentration of chloral hydrate, the absence of both visible particulate matter, or color and/or odor changes and the compliance with microbiological attributes of non-sterile pharmaceutical products. RESULTS: At least 98% of the initial chloral hydrate concentration remained throughout the 180-day study period. There were no detectable changes in color, odor, specific gravity and pH and no visible microbial growth. These results were not affected by storage, room or refrigeration conditions or by the frequent opening or closing of the multi-dose containers. CONCLUSIONS: Extemporaneously compounded 7% chloral hydrate syrup was stable for at least 180 days when stored in mono or multi-dose light-resistant glass containers at room temperature and under refrigeration.

Eudragit E100 as a drug carrier: the remarkable affinity of phosphate ester for dimethylamine.

Therapeutic agents containing phosphate groups in their molecules have increasing therapeutic impact. The object of this study was to characterize the cationic polyelectrolyte Eudragit E100 (EuE100) as a carrier for drugs containing phosphate groups, using dexamethasone phosphate (DP) as a model. A series of EuE100-DP complexes was obtained by acid-base reaction in which DP neutralized 12.5-75% of the basic groups of EuE100. The solids obtained after solvent evaporation revealed by spectroscopic characterization the complete reaction between the components through the ionic interaction between the amine groups of EuE100 and the phosphate groups of DP. The reversibility of the counterion condensation, evaluated through the proton-withdrawing effect produced by the ionic exchange generated by titration with NaCl, showed a remarkable high affinity between EuE100 and DP. In line, drug delivery in bicompartimental Franz cells toward water as receptor medium was very slow (2% in 6 h). However, it was increased as water was replaced by NaCl solution, which upon diffusion generates ionic exchange. A sustained release of DP with noticeable zero order kinetics accounted for a remarkable high affinity, mainly due to the electrostatic attraction. The release rate remains constant regardless of the saline concentration of the media. Besides, the delivery control is maintained even in gastric simulated fluid, a property not informed previously for EuE100 complexes.

Multinuclear solid state NMR investigation of two polymorphic forms of ciprofloxacin-saccharinate.

Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D (1)H-(1)H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the (1)H-(1)H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.

Biowaiver monographs for immediate release solid oral dosage forms: ciprofloxacin hydrochloride.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing ciprofloxacin hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ciprofloxacin hydrochloride's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and BA data indicate that ciprofloxacin hydrochloride is a BCS Class IV drug. Therefore, a biowaiver based approval of ciprofloxacin hydrochloride containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

Crystallographic, thermal and spectroscopic characterization of a ciprofloxacin saccharinate polymorph.

A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions.

Biowaiver monographs for immediate release solid oral dosage forms: amitriptyline hydrochloride.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing amitriptyline hydrochloride are reviewed. Its therapeutic uses, its pharmacokinetic properties, the possibility of excipient interactions and reported BE/bioavailability (BA) problems are also taken into consideration. Literature data indicates that amitriptyline hydrochloride is a highly permeable active pharmaceutical ingredient (API). Data on the solubility according to the current Biopharmaceutics Classification System (BCS) were not fully available and consequently amitriptyline hydrochloride could not be definitively assigned to either BCS Class I or BCS Class II. But all evidence taken together, a biowaiver can currently be recommended provided that IR tablets are formulated with excipients used in existing approved products and that the dissolution meets the criteria defined in the Guidances.

Release kinetics and up-take studies of model fluoroquinolones from carbomer hydrogels.

Hydrogels of carbomer (C) loaded with model slightly soluble fluoroquinolone antimicrobials (AMFQ), norfloxacin (I) and ciprofloxacin (II) were prepared to evaluate their physical and delivery properties. Thus, dispersions of 0.25% of C loaded with 0.2-0.5 mol equivalents of AMFQ and 0.2-0.5 mol equivalents of NaOH yielded pseudoplastic hydrogels with a high negative electrokinetic potential and good physical stability. Concentration of AMFQ in the hydrogels was, respectively, 7.2 and 34 times higher than I and II aqueous solubility, indicating a high increase in aqueous compatibility. Release of AMFQ in bicompartimetal Franz type cell occurred by zero order kinetics. Delivery rate constant (k(0)) was five to six times higher as water was replaced by NaCl solution as receptor medium. Release in agar dishes revealed that, even under high dilution, delivery remains modulated. Intestinal absorption flux coefficient in everted rat intestine (k(U)) were measured with reference solutions (RS) of free AMFQ (k(U)(RS) II>k(U)(RS) I) and with hydrogels (H), in which the pattern was reversed since k(U)(H) I>k(U)(H) II. As expected k(U)(H) II was 0.55 times lower than k(U)(RS) II. However, k(U)(H) I was 1.37 times higher than its reference, which cannot be explained from the analysis of k(0) and k(U)(RS) alone. Hydrogels C-AMFQ behave as a reservoir of AMFQ able to deliver it at a constant rate and would be useful to design topical and or systemic dosage forms.