RESUMEN
Ageing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline "Studies in support of special populations, geriatrics", the ICH Q8 guideline "Pharmaceutical development", the EMA good practice guide on "Risk minimisation and prevention of medication errors" and the forthcoming EMA CHMP QWP reflection paper on the "Quality aspects (pharmaceutical development) of medicines for older people". In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development.
Asunto(s)
Aprobación de Drogas/legislación & jurisprudencia , Diseño de Fármacos , Geriatría/normas , Motivación , Anciano , Aprobación de Drogas/métodos , Descubrimiento de Drogas/legislación & jurisprudencia , Descubrimiento de Drogas/métodos , Descubrimiento de Drogas/normas , Etiquetado de Medicamentos/legislación & jurisprudencia , Etiquetado de Medicamentos/métodos , Etiquetado de Medicamentos/normas , Almacenaje de Medicamentos/legislación & jurisprudencia , Almacenaje de Medicamentos/métodos , Almacenaje de Medicamentos/normas , Europa (Continente) , Geriatría/métodos , Humanos , Errores de Medicación/legislación & jurisprudencia , Errores de Medicación/prevención & control , Comprimidos/normasRESUMEN
The purpose of this work is to study the ability of a new biodegradable polyurethane PU(TEG-HMDI) obtained by reaction of triethylene glycol (TEG) with 1,6-hexamethylene diisocyanate (HMDI) to act as matrix forming polymer for controlled release tablets and to estimate its percolation threshold in a matrix system. Matrix tablets weighing 250 mg were prepared by direct compression with 10-30% wt/wt of PU(TEG-HMDI) and anhydrous theophylline as model drug. Release studies were carried out using the paddle method. The results were analyzed using the kinetics models of Higuchi, Korsmeyer-Peppas, and Peppas and Sahlin. These studies confirm the existence of an excipient percolation threshold between 10 and 20 % wt/wt of PU(TEG-HMDI) for the different batches prepared. It has been observed that the new biodegradable polyurethane PU(TEG-HMDI) shows adequate compatibility as well as a high ability to control the drug release.
Asunto(s)
Plásticos Biodegradables/química , Excipientes/química , Modelos Moleculares , Poliuretanos/química , Teofilina/química , Vasodilatadores/química , Plásticos Biodegradables/síntesis química , Fenómenos Químicos , Cianatos/química , Preparaciones de Acción Retardada/química , Difusión , Composición de Medicamentos , Excipientes/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Indicadores y Reactivos/química , Isocianatos , Cinética , Fenómenos Mecánicos , Estructura Molecular , Peso Molecular , Polietilenglicoles/química , Poliuretanos/síntesis química , Solubilidad , Comprimidos , ViscosidadRESUMEN
The synthesis, characterization, and some properties of new glutathione-mediated biodegradable sugar-based copolyurethanes are described. These copolyurethanes were obtained by polyaddition reaction of mixtures of 2,2'-dithiodiethanol (DiT) and 2,3,4-tri-O-benzyl-L-arabinitol (ArBn) or 2,3,4-tri-O-methyl-L-arabinitol (ArMe) to 1,6-hexamethylene diisocyanate (HMDI). The copolymer compositions were studied by elemental microanalyses and (1)H NMR, revealing that the content of the copolymer units is in all cases very similar to that of their corresponding feed. The PU(DiT-HMDI) homopolymer exhibited a high crystallinity, but the introduction of the arabinitol-based diols led to a reduction in the crystallinity of the copolymers. In their TG curves, the copolymers exhibited a mixed trend of the related homopolymers, and all of them were thermally stable, with degradation temperatures above 220 degrees C. The degradation properties of the macromolecules under physiological conditions in the presence of glutathione were tested. All the copolyurethanes proved to be biodegradable under the experimental conditions (pH = 7.02 and 37 degrees C). The degradation pattern of the copolymers depended not only on the dithiodiethanol (DiT) reactive units ratio in the polymer backbone, but also on the crystallinity of the macromolecule.