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1.
Int J Pharm Pract ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965914

RESUMEN

OBJECTIVES: This study aimed to investigate and provide insight into the prevalence and patterns of off-label drug use in the pediatric population from the perspective of community pharmacists, addressing the existing data gap in a developing setting. METHODS: A questionnaire-based cross-sectional study was conducted on Albanian community pharmacists in June 2021. The online administered survey explored the participants' demographic details, perceptions, and experiences with off-label prescriptions in pediatric patients. The statistical analysis conducted on the survey data comprised the construction of frequency tables and the application of the chi-square test for independence. KEY FINDINGS: Three hundred and thirty-six community pharmacists nationwide completed the survey, out of which 186 (55.3%) were practiced in Tirana, the capital of Albania. Over 80% of surveyed pharmacists (n = 275) had encountered off-label drug prescriptions in pediatric patients, yet only 40% of participants reported dispensing medicines for off-label use. Community pharmacists reported that general pediatricians tended to prescribe off-label medications more frequently than pediatric subspecialists or general practitioners. It was found that off-label prescriptions were more frequently observed among children aged between 2 and 11 years. Antibiotics were the most reported medicines for off-label use in this study mentioned in almost all off-label categories. CONCLUSIONS: Prescribing medicines for unapproved uses for the treatment of pediatric patients is present in community settings in Albania. This indicates the need for further data collection and analysis to understand off-label practices in our country's pediatric population comprehensively.

3.
Mater Sociomed ; 29(2): 138-142, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28883779

RESUMEN

AIM: To assess the level of knowledge of the adult users of non-steroidal anti-inflammatory drugs (NSAIDs) regarding their side effects and the socio-demographic factors associated with the use of these drugs in the adult population of Albania. METHODS: This was a cross-sectional study including a representative sample of 199 individuals aged ≥18 years (77% women; overall mean age: 30.3±10.0 years; overall response rate: 90%) who were users of NSAIDs recruited in ten different pharmacies in Tirana municipality during April-May 2015. A self-administered questionnaire contained basic socio-demographic information and questions about NSAIDs use, their types, participants' knowledge about NSAIDs side effects and their interaction with other drugs. RESULTS: In 56% of the cases, NSAIDs were taken by participants' own decisions, whereas in about 29% of the cases these drugs were prescribed by physicians. Acetaminophen, ketoprofen and ibuprofen were the most frequently used NSAIDs. Overall, 51% of participants thought NSAIDs could cause allergic reactions, whereas one third or fewer were aware of each of the following side effects: upper and lower gastrointestinal bleeding, hypertension, gastritis, kidney failure, myopathy, osteoporosis. About one third of participants were aware of NSAIDs-other drug interactions, whereas some of them were already taking contraindicated drugs. No significant differences were noticed regarding sex, age, educational level, employment status and marital status, with very few exceptions. CONCLUSION: Our findings indicate limited knowledge about NSAIDs side effects and their interaction with other drugs among the Albania adult population, which is a cause of concern.

4.
Curr Pharm Des ; 22(32): 4959-4974, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27464724

RESUMEN

Drugs and excipients used for pharmaceutical applications generally exist in the solid (crystalline or amorphous) state, more rarely as liquid materials. In some cases, according to the physicochemical nature of the molecule, or as a consequence of specific technological processes, a compound may exist exclusively in the amorphous state. In other cases, as a consequence of specific treatments (freezing and spray drying, melting and co-melting, grinding and compression), the crystalline form may convert into a completely or partially amorphous form. An amorphous material shows physical and thermodynamic properties different from the corresponding crystalline form, with profound repercussions on its technological performance and biopharmaceutical properties. Several physicochemical techniques such as X-ray powder diffraction, thermal methods of analysis, spectroscopic techniques, gravimetric techniques, and inverse gas chromatography can be applied to characterize the amorphous form of a compound (drug or excipient), and to evaluate its thermodynamic stability. This review offers a survey of the technologies used to convert a crystalline solid into an amorphous form, and describes the most important techniques for characterizing the amorphous state of compounds of pharmaceutical interest.


Asunto(s)
Composición de Medicamentos , Preparaciones Farmacéuticas/química , Termodinámica , Química Física , Cristalización , Estabilidad de Medicamentos , Preparaciones Farmacéuticas/síntesis química
5.
J Infect Dev Ctries ; 9(1): 94-8, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25596577

RESUMEN

INTRODUCTION: Health institutions in Albania have recently reported an increase in antibiotic misuse and microbial resistance. Until now, there have been no comprehensive studies that analyzed the overall use of antibiotics in Albania. The aim of this study was to analyze the overall antibiotic use in Albania between 2011 and 2012, using standardized methodology of measurement, based on World Health Organization guidelines. METHODOLOGY: Data from 2011 and 2012 on antibiotic use from ambulatory and hospital sector were examined. Antibiotics were divided based on anatomic therapeutic chemical classification. Defined daily dose (DDD) for each drug was assigned, and DDD per 1,000 inhabitants per day (DID) was used as a measurement unit. In cases of antibiotic combinations for which DDD were not available, unit doses were assigned. RESULTS: In 2011-2012, total antibiotic use decreased from 24.25 to 20.66 DID. Penicillin's were the most used antibiotic class, with 10.62 DID (2011) and 10.51 DID (2012). Tetracycline use decreased from 5.45 DID (2011) to 0.98 DID (2012). Macrolides increased from 1.36 to 1.88 DID, quinolones from 1.72 to 2.51 DID. The overall antibiotic use was significantly higher than the reimbursed antibiotic use ­ 3.17 DID (2011) and 2.79 DID (2012) ­ based on the official data for the same period. CONCLUSIONS: This study enables policymakers to further analyze the quality of antibiotic prescriptions and draw comparisons to other countries. The analyzed data suggest there are different factors influencing out-of-pocket use of antibiotics and wrongly prescribed antibiotics. Further studies are necessary to evaluate these factors.


Asunto(s)
Antibacterianos/uso terapéutico , Utilización de Medicamentos , Albania , Instituciones de Atención Ambulatoria , Prescripciones de Medicamentos/normas , Política de Salud , Hospitales , Humanos
6.
Open Access Maced J Med Sci ; 3(2): 341-4, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-27275248

RESUMEN

AIM: The study aim is to evaluate the cost-effectiveness of thrombolytic treatment in acute MI comparing with anticoagulants therapy and between each other thrombolytic (SK, r-Pa). MATERIAL AND METHODS: We used a prospective registry of all patients admitted for acute myocardial infarction in intensive care units in Tirana. The average drugs cost was calculated for the hospitalization period in Albanian money (ALL). Survival and life quality were estimated by phone contact 1 year after acute MI. RESULTS: Anticoagulant group cost is 23865.3 ALL (170.5€), SK group cost is 54148.63 ALL (386.7€), r-Pa group has a cost of 92184.90 ALL (658.5€). In the group treated with SK the hospital survival is 100%, while in the control group 88.8%. Reteplase group has a lower period of stay in hospital than SK group 13.04 days vs. 17.97 days, mean age in group treated with r-Pa is 64.29 ± 10.03 approximate with anticoagulant group mean age 64.17 ± 11.08; differ significantly with SK group mean age 56.75 ± 10.04. Survival after 1 year was 96.4% for r-Pa and 96.9% SK. CONCLUSIONS: SK and r-Pa are successful thrombolytics with high effectiveness. It is gained a higher survival with the thrombolytic treatments. Reteplase is well tolerated in older patients than SK, is easier to apply than Streptokinase, but has higher cost.

7.
Pharm. pract. (Granada, Internet) ; 12(4): 0-0, oct.-dic. 2014. tab
Artículo en Inglés | IBECS | ID: ibc-130541

RESUMEN

Objective: This study sought to explore the knowledge and attitudes of parents on the use of antibiotics among children that could serve as baseline data and provide further insight in planning and developing strategies for local health education purposes. Methods: A cross-sectional survey involving 500 parents who attended community pharmacies in Tetovo, Republic of Macedonia, was conducted using a self-administered questionnaire from October 2013 to January 2014. The questionnaire included demographics, knowledge and attitude statements of parents towards antibiotics. The data collected were analyzed using SPSS program, version 19.0. Descriptive statistics was used to summarize the data. In all statistical analyses, a p-value of <0.05 was considered statistically significant. Results: Nearly 40% of the parents demonstrated a moderate level of knowledge. The highest correct response in the knowledge part was the awareness of parents in using antibiotics to treat a bacterial infection (61.2%). However, most of the parents did not know that antibiotics cannot cure viral infections (59.6%). About 48.2% of the parents were aware of the antibiotic resistance as s result of the overuse. Concerning attitudes, 60.8% reported keeping any leftover antibiotics, 77.0% agreed that taking antibiotics when having cold symptoms could help their children recover faster, while, 74.6% wrongly agreed with the statement of appropriate use of antibiotics for prophylaxis’ measure. Conclusions: This study has documented the main areas that merit attention when parental knowledge on antibiotic use for their children is the concern, reflecting in some inappropriate attitudes as well. The findings highlight the need to devise effective interventions to decrease misconceptions regarding antibiotic use and to increase parents’ awareness for the risks of inappropriate use of antibiotics in children specifically and in the community at large (AU)


Objetivo: Este estudio intentó explorar el conocimiento y actitudes de padres sobre el uso de antibióticos en niños para servir como punto de partida y proporcionar futuro conocimiento para planear y desarrollar estrategias de educación local de salud. Métodos: Se realizó un estudio transversal que incluyo a 500 pacientes que visitaron farmacias comunitarias en Tetovo, República de Macedonia mediante el uso de un cuestionario auto-administrado entre octubre 2013 y enero 2014. El cuestionario incluía datos demográficos y afirmaciones sobre conocimiento y actitud de los padres hacia los antibióticos. Los datos recogidos se analizaron usando el programa SPSS versión 19.0. Se usó estadística descriptiva para resumir los datos. En todos los análisis estadísticos se consideró estadísticamente significativo un valor de p <0,05. Resultados: Casi el 40% de los padres demostraron tener un nivel moderado de conocimiento. La respuesta correcta más frecuente en la parte de conocimiento era la consciencia de los padres de que los antibióticos se usan para tratar una infección bacteriana (61,2%). Sin embargo, la mayoría de los padres no sabían que los antibióticos no curan infecciones víricas (59,6%). Alrededor del 48,2% de los padres sabían que las resistencias a los antibióticos resultan de su sobreutilización. En relación a las actitudes, el 60,8% comunicó guardar los restos de los antibióticos, el 77,0% aceptó que tomar antibióticos cuando sus hijos tienen síntomas de resfriado puede ayudarles a recuperarse más rápidamente, mientras que el 74,6% estaba de acuerdo con la medida equivocada de usar antibióticos como medida profiláctica. Conclusiones: Este estudio documentó las áreas principales que merecen atención en relación al conocimiento parenteral sobre uso de antibióticos para sus hijos, reflejando también algunas actitudes inadecuadas. Los hallazgos apuntan a la necesidad de diseñar intervenciones efectivas para disminuir los conceptos equivocados sobre el uso de antibióticos y aumentar el conocimiento de los padres sobre los riesgos del uso inapropiado de antibióticos en niños específicamente y en la comunidad en general (AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Conocimientos, Actitudes y Práctica en Salud , Antibacterianos/uso terapéutico , Farmacias/organización & administración , Resistencia a Medicamentos , Padres/educación , Estudios Transversales , Encuestas y Cuestionarios
8.
Int J Pharm ; 473(1-2): 536-44, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25064728

RESUMEN

The purpose of this study was to investigate the effect of pH and method of crystallization on the solid physical form of indomethacin (IDM). IDM, a non steroidal anti-inflammatory drug poorly soluble in water, underwent two different crystallization methods: crystallization by solvent evaporation under reduced pressure at 50.0°C (method A), and crystallization by cooling of solution from 50.0 to 5.0°C (method B). In both cases, several aqueous ethanolic solutions of IDM of different pHs were prepared. pHs were adjusted by adding acidic solutions (HCl 2M) or alkali (NaOH or NH4OH 2M) to an aqueous ethanolic solution of IDM. Thus, several batches were recovered after crystallization. The chemical stability of IDM was verified through (1)H NMR and mass spectroscopy (FIA-ESI-MS), that revealed that IDM degraded in strong alkali media (pH ≥ 12). Crystals obtained under different crystallization conditions at pHs of 1.0, 4.5, 7.0, 8.0, 10.0 and chemically stable were thus characterized for crystal habit by scanning electron microscopy, for thermal behaviour by differential scanning calorimetry, and thermogravimetry, and for solid state by X-ray powder diffractometry. Under the Method A, IDM always crystallized into pure metastable alpha form when solutions were acidified or alkalized respectively with HCl and NH4OH. On the contrary, in presence of NaOH, IDM crystallized under a mixture of alpha and sodium trihydrate form, because the presence of the sodium counter ion orientates the crystallization towards the formation of the trihydrate salt. Under the method B, at pH of 1.0, IDM crystallized under the alpha form; at pH 4.5, IDM crystallized under the form alpha in presence of some nuclei of gamma form; at pH 7.0, 8.0, and 10.0 for NH4OH, IDM crystallized under the most stable polymorph gamma form, whereas in presence of NaOH, a mix of alpha, and salt forms was formed whatever the pH of the solution.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Indometacina/química , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Cristalización , Calor , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Difracción de Polvo , Presión , Soluciones , Termogravimetría , Difracción de Rayos X
9.
Pharm Pract (Granada) ; 12(4): 467, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25580168

RESUMEN

OBJECTIVE: This study sought to explore the knowledge and attitudes of parents on the use of antibiotics among children that could serve as baseline data and provide further insight in planning and developing strategies for local health education purposes. METHODS: A cross-sectional survey involving 500 parents who attended community pharmacies in Tetovo, Republic of Macedonia, was conducted using a self-administered questionnaire from October 2013 to January 2014. The questionnaire included demographics, knowledge and attitude statements of parents towards antibiotics. The data collected were analyzed using SPSS program, version 19.0. Descriptive statistics was used to summarize the data. In all statistical analyses, a p-value of <0.05 was considered statistically significant. RESULTS: Nearly 40% of the parents demonstrated a moderate level of knowledge. The highest correct response in the knowledge part was the awareness of parents in using antibiotics to treat a bacterial infection (61.2%). However, most of the parents did not know that antibiotics cannot cure viral infections (59.6%). About 48.2% of the parents were aware of the antibiotic resistance as s result of the overuse. Concerning attitudes, 60.8% reported keeping any leftover antibiotics, 77.0% agreed that taking antibiotics when having cold symptoms could help their children recover faster, while, 74.6% wrongly agreed with the statement of appropriate use of antibiotics for prophylaxis' measure. CONCLUSIONS: This study has documented the main areas that merit attention when parental knowledge on antibiotic use for their children is the concern, reflecting in some inappropriate attitudes as well. The findings highlight the need to devise effective interventions to decrease misconceptions regarding antibiotic use and to increase parents' awareness for the risks of inappropriate use of antibiotics in children specifically and in the community at large.

10.
Drug Dev Ind Pharm ; 38(9): 1128-33, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22188183

RESUMEN

A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol® P as solubilizing agent and permeation enhancer, was emulsified with Labrafil® as oil phase and Labrasol®/Capryol™ 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz's cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol® P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol® P. These two last formulations are those showing the lower skin retention.


Asunto(s)
Antioxidantes/metabolismo , Emulsionantes/química , Glicoles de Etileno/química , Excipientes/química , Quercetina/metabolismo , Piel/química , Administración Cutánea , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Química Farmacéutica , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/química , Fármacos Dermatológicos/metabolismo , Difusión , Estabilidad de Medicamentos , Emulsiones , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Cinética , Tamaño de la Partícula , Permeabilidad , Quercetina/administración & dosificación , Quercetina/química , Piel/efectos de los fármacos , Solubilidad , Sus scrofa , Viscosidad
11.
J Pharm Sci ; 100(7): 2610-22, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21254066

RESUMEN

Nicergoline (NIC), a poorly water-soluble semisynthetic ergot derivative, was crystallized from several organic solvents, obtaining two different polymorphic forms, the triclinic form I and the orthorhombic form II. NIC samples were then characterized by several techniques such as (13)C cross-polarization magic angle spinning solid-state spectroscopy, room-temperature and high-temperature X-ray powder diffraction, differential scanning calorimetry, and by analysis of weight loss, solvent content, powder density, morphology, and particle size. Solubility and intrinsic dissolution rates determined for the two polymorphic forms in water and hydrochloride solutions (HCl 0.1 N) were always higher for form II than for form I, which is actually the form used for the industrial preparation of NIC medicinal products. Preformulation studies might encourage industry for the evaluation of polymorph II, as it is more suitable for pharmaceutical applications. Results in drug delivery, as well as those obtained by the above-mentioned techniques, and the application of Burger-Ramberger's rules make it possible to conclude that there is a thermodynamic relation of monotropy between the two polymorphs. This last assumption may help formulators in predicting the relative stability of the two forms.


Asunto(s)
Nicergolina/química , Solventes/química , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Cromatografía de Gases , Cristalización , Cristalografía por Rayos X , Concentración de Iones de Hidrógeno , Cinética , Espectroscopía de Resonancia Magnética , Microscopía Electrónica de Rastreo , Estructura Molecular , Tamaño de la Partícula , Difracción de Polvo , Solubilidad , Tecnología Farmacéutica/métodos , Temperatura
12.
Int J Pharm ; 398(1-2): 61-72, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-20655373

RESUMEN

The present work assessed the physical interactions between several aryl propionic acid derivatives and polyvinyl(pyrrolidone) K30 (PVP), stored together at 298+/-0.5K at different relative humidities (RH 55, 75 and 86%). Results were compared to those obtained at low RH (22%), published in a previous paper. The water uptake percentage of binary mixtures were intermediate between that of pure PVP and pure drugs. By X-ray powder diffraction, for all the drugs, it was possible to note a marked decrease in crystallinity degree, in particular at highest RH%. The loss in crystallinity degree may be considered an evidence of the physicochemical interaction between the polymer and the drug, supporting the formation of a solid dispersion. By high-resolution (1)H solid-state NMR spectrometry, it was possible to observe an increase of drug-polymer interaction with aging, with the only exception of ibuprofen. Molecular docking proved the establishment of Van der Waals and electrostatic interactions for all the mixtures, and for mixtures with fenbufen and naproxen, also hydrogen bonds. The application of Gordon-Taylor rule to the thermal analysis revealed that the requirement of volume additivity of this rule was not fulfilled for any mixture, and a negative deviation from theoretical behaviour was always observed. The hydration of drug-PVP mixtures had important repercussion on drug solubility and intrinsic dissolution rate (IDR). In general, an increase in water solubility and consequently an increase in IDR were observed, with few exceptions, at highest RH%.


Asunto(s)
Humedad , Povidona/química , Povidona/farmacocinética , Propionatos/química , Propionatos/farmacocinética , Disponibilidad Biológica , Evaluación Preclínica de Medicamentos/métodos , Interacciones Farmacológicas , Difracción de Rayos X/métodos
13.
Int J Pharm ; 390(2): 142-9, 2010 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-20117196

RESUMEN

The aim of the present work was to investigate the technological properties and the compression behaviour of the anhydrous and hydrate solid forms of sodium naproxen. Among the hydrates, the following forms were studied: the monohydrate (MSN), obtained by dehydrating a dihydrated form (DSN) in each turn obtained by exposing the anhydrous form at 55% RH; a dihydrated form (CSN) obtained by crystallizing sodium naproxen from water, the tetrahydrated form (TSN) obtained by exposing the anhydrous form at 75% RH. The physico-chemical (crystalline form and water content), the micromeritic (crystal morphology and particle size) and the mechanical properties (Carr's index, apparent particle density, compression behaviour, elastic recovery and strength of compact) were evaluated. We made every effort to reduce differences in crystal habit, particle size and distribution, and amount of absorbed water among the samples, so that the only factors affecting their technological behaviour would be the degree of hydration and the crystalline structure. This study demonstrates a correlation between the compression behaviour and the water molecules present in the crystalline structures. The sites where water molecules are accommodated in the crystalline structure behave like weak points where the crystalline lattice yields under compression. The crystal deformability is proportional to the number of water molecules in these sites; the higher the water content, the higher the deformability, because the densification behaviour changes from a predominantly elastic deformation to a plastic behaviour. The deformability is responsible for a higher densification tendency that favours larger interparticle bonding areas that may explain the better tabletability of TSN and CSN.


Asunto(s)
Fuerza Compresiva , Cristalización/métodos , Composición de Medicamentos/métodos , Naproxeno/química , Agua/química , Tamaño de la Partícula , Resistencia a la Tracción
14.
J Pharm Sci ; 98(11): 4216-28, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19645003

RESUMEN

The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and (13)C-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, NAP, and the least for FEN. The interaction of comelted drug and PVP was studied by differential scanning calorimetry by applying the Gordon-Taylor equation, which revealed that small molar drug volumes may favour the drug diffusion through the PVP amorphous chains increasing the polymer free volume and decreasing the mixture T(g). The molecular docking study revealed that intermolecular energy is mainly due to the contribution of van der Waals energy component, causing the differences among the drugs, and is related to the drug-PVP surface contact area in the complex formed. Solid-state kinetic study demonstrated that IBP molecules are involved in a three-dimensional diffusion mechanism within the polymer favoured by its low molar volume that reduces molecular hindrance, and by the weakness of its crystal lattice, which facilitates crystallinity loss and stabilisation of the amorphous phase.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Rastreo Diferencial de Calorimetría/métodos , Espectroscopía de Resonancia Magnética/métodos , Povidona/química , Difracción de Rayos X/métodos , Isótopos de Carbono , Cristalización , Estabilidad de Medicamentos , Flurbiprofeno/química , Calor , Humedad , Enlace de Hidrógeno , Ibuprofeno/química , Cetoprofeno/química , Estructura Molecular , Peso Molecular , Naproxeno/química , Transición de Fase , Fenilbutiratos/química , Polímeros/química , Electricidad Estática
15.
Eur J Pharm Biopharm ; 70(1): 345-56, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18539444

RESUMEN

The aim of this work is to establish a correlation between water uptake by anhydrous sodium naproxen (ASN) at two different relative humidities and modifications in tableting and densification behaviour under hydration. Water uptake was evaluated at different relative humidities. Models for the hydration kinetics of ASN at 55% and 86%, corresponding to the formation of the dihydrated and tetrahydrated forms, respectively, were evaluated assuming Eyring's dependence on temperature. Tabletability, compressibility, compactibility, and densification behaviour were determined using an instrumented single punch tablet machine. Kinetic data are consistent with a model where water molecules enter the crystal preferentially along hydrophilic tunnels existing in the crystal structure and corresponding to the propionate side chain. Water inclusion perturbs the crystallographic structure, causing slight structural changes according to the amount and associated to an increase in entropy. The interposition of water molecules between sodium naproxen molecules weakens intermolecular bonds, and these sites can behave like sliding planes under compression. Such structural changes may explain the improved compression behaviour and modified densification propensity mechanism. Kinetic data describing the water hydration mechanism of ASN explain in an original way the improved tableting and densification properties under hydration.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Naproxeno/química , Agua/química , Química Farmacéutica , Fuerza Compresiva , Cristalización , Entropía , Humedad , Cinética , Modelos Químicos , Comprimidos , Tecnología Farmacéutica/métodos , Temperatura , Resistencia a la Tracción
16.
J Pharm Sci ; 97(12): 5263-73, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18398910

RESUMEN

In the present work, authors produced tablets of anhydrous sodium naproxen by wet granulation using a high-shear mixer-granulator. Drug hydrated to the tetrahydrated form, as observed by X-ray powder diffractometry. After wet granulation, authors then performed two different drying procedures, obtaining granules of different water content and crystallographic characteristics. The first procedure dried granules in the high-shear mixer-granulator by applying vacuum at room temperature (batch A), while the second employed the same apparatus and time, under vacuum at 40 degrees C (batch B). X-ray powder diffractometry revealed that the sodium naproxen (SN) contained in batch A granules was a mixture of dihydrated and tetrahydrated forms (as demonstrated by the coexistence of peaks typical of both hydrated forms), while that of batch B granules was a mixture of monohydrated and tetrahydrated forms. This means that differences in drying procedures could lead to products of different crystallographic properties. The behavior under compression was evaluated, revealing that batch A offered the best tabletability and compressibility. These results make it possible to conclude that differences in the crystallographic properties and water content of SN are such that different hydration/drying processes can alter the drug crystal form and thus the tabletability of the resulting granules.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Naproxeno/química , Polvos , Sensibilidad y Especificidad , Comprimidos , Resistencia a la Tracción , Difracción de Rayos X
17.
J Pharm Biomed Anal ; 47(2): 422-8, 2008 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-18295427

RESUMEN

The aim of this work was to develop and validate a method to assess the dissolution behaviour of rociverine sugar-coated tablets. In our laboratories, an HPLC-MS in reverse phase method of analysis was developed for the dosage of unknown rociverine solution. This analytical method was applied to determine the dissolution rate of rociverine tablets produced by the industrial procedure, because there is no official method description. Dissolution tests were carried out in sink conditions as follows: dissolution medium HCl 0.01 N, paddle rotation speed 50 rpm and vessel volume 1000 ml. The dissolution test gave satisfactory results: 95% of the drug was dissolved within 30 min and drug dissolution was concluded after 60 min. The method was demonstrated to be adequate for Quality Control of rociverine tablets. Validation was inferred from specificity, linearity, precision, accuracy and robustness.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Ácidos Ciclohexanocarboxílicos/análisis , Espectrometría de Masas/métodos , Parasimpatolíticos/análisis , Comprimidos/química , Ácidos Ciclohexanocarboxílicos/química , Ácidos Ciclohexanocarboxílicos/farmacocinética , Ácido Clorhídrico/química , Parasimpatolíticos/química , Reproducibilidad de los Resultados , Solubilidad , Comprimidos Recubiertos
18.
Drug Dev Ind Pharm ; 33(12): 1308-17, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18097804

RESUMEN

Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant. Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression.


Asunto(s)
Celulosa/análogos & derivados , Metronidazol/química , Tecnología Farmacéutica , Celulosa/química , Polvos , Comprimidos , Resistencia a la Tracción
19.
Drug Dev Ind Pharm ; 33(2): 121-31, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17454043

RESUMEN

Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.


Asunto(s)
Composición de Medicamentos/instrumentación , Metronidazol/química , Tecnología Farmacéutica/instrumentación , Acetatos/química , Antiinfecciosos/química , Butanoles/química , Celulosa/química , Fuerza Compresiva , Cristalización , Desecación/métodos , Composición de Medicamentos/métodos , Industria Farmacéutica/métodos , Pruebas de Dureza/métodos , Lactosa/química , Tamaño de la Partícula , Porosidad , Polvos , Solventes/química , Comprimidos , Tecnología Farmacéutica/métodos , Agua/química , Humectabilidad , Difracción de Rayos X/métodos
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