RESUMEN
The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices. Prilling tended to be susceptible to increased melt viscosity. Direct compression was not applicable for mini-matrix production due to poor powder flow. In general MPT release from all matrices was affected by its loading and the size of the units/particles. Processing of GB-MPT mixtures by different techniques did not lead to different drug release rates and patterns, while in case of GPS differently obtained matrices provided diverse MPT release outcomes. Matrices based on GB tended to have higher porosity compared to ones composed of GPS and thus most of the GB-based formulations showed faster drug delivery. FT-IR analysis revealed no interactions between primary components used for matrix production and Raman mapping outlined uniform MPT distribution throughout the units. DSC and X-ray studies revealed significant changes in the crystallinity of glycerides after storage under room conditions (GPS samples) and at increased temperature (GB and GPS samples), which was correlated to the changes seen in drug release rate and pattern after storage. Media composition in general tended to insignificantly affect GB matrices, while in case of GPS matrices increasing the pH and presence of biorelevant compounds induced faster drug release.
Asunto(s)
Antiarrítmicos/química , Metoprolol/química , Tecnología Farmacéutica/métodos , Química Farmacéutica/métodos , Preparaciones de Acción Retardada , Industria Farmacéutica , Liberación de Fármacos , Almacenaje de Medicamentos , Excipientes/química , Glicéridos/química , Lípidos/química , Factores de TiempoRESUMEN
Mini-tablets are gaining great attention as systems capable of being formulated into multiple unit systems providing a specific drug release pattern. Within the presented research a combined, multiple-unit system, based on different coated matrix mini-tablets, has been developed in order to achieve 24-h specific sigmoid extended release of the model drug paliperidone. The mini-tablets were based on different amounts of polyvinyl acetate/polyvinyl pyrolidone mixture as the matrix former, providing extended release, and two different types of pH-dependent, acrylic polymer coatings, providing delay in release onset, and thus achieving the required specific sigmoid release pattern imposed by the original drug on the market. The selected formulation proved to be consistent with pharmacopoeial requirements. It was also in vitro similar (f2) to the original drug and the theoretical linear release profile, as well as robust and reproducible regarding in vitro release in different fasted gastro-intestinal conditions. This is proof of concept that 24-h, specific, and almost linear release profile of drugs with high solubility can be achieved by employing technology of coated matrix mini-tablets.
Asunto(s)
Palmitato de Paliperidona/química , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa/química , Metacrilatos/química , Polímeros/química , Solubilidad , ComprimidosRESUMEN
INTRODUCTION: Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system. AREAS COVERED: Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems. EXPERT OPINION: Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.