Předkládaný přehledový článek je kompilací několika zahraničních rešeršních a experimentálních prací, stejně jako několika směrnic autorit, které se zabývají fenoménem dose dumpingu pevných lékových forem s modifikovaným uvolňováním léčiva. Cílem publikace je tuto často opomíjenou problematiku představit širšímu domácímu publiku. Práce se věnuje dvěma základním typům dose dumpingu, tj. alkoholem vyvolaný dose dumping a potravou vyvolaný dose dumping. Obsahuje základní faktory ovlivňující tento jev i jejich formulační řešení, která je možné pro jeho eliminaci využít. V neposlední řadě jsou zmíněny také současné požadavky autorit především na testování nově uváděných přípravků s potenciálním rizikem dose dumpingu.
The presented review article is a compilation of several foreign reviews and experimental papers, as well as several authority guidelines, which deal with the phenomenon of dose dumping of solid dosage forms with modified drug release. The aim of the publication is to present this often-neglected issue to a wider domestic audience. The work deals with two basic types of dose dumping, i.e., alcohol-induced dose dumping and food-induced dose dumping. It contains basic factors affecting this phenomenon as well as possible formulation solutions that can be used to eliminate it. Last but not least, the current requirements of the authorities are also mentioned, especially for testing newly introduced products with the presumed potential risk of dose dumping.
- MeSH
- chemie farmaceutická MeSH
- ethanol MeSH
- lékové formy MeSH
- léky s prodlouženým účinkem * MeSH
- uvolňování léčiv MeSH
- Publikační typ
- přehledy MeSH
Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10-30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices' evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10-20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.
- Publikační typ
- časopisecké články MeSH
The use of solid oral dosage forms depends on the degree of bioavailability of the active pharmaceutical ingredient. The rate and extent of the drug released from the dosage form and subsequently dissolved in the gastrointestinal fluids greatly affects its fate in the human body. In vitro dissolution test may provide an in-depth understanding of a drug formulation's behaviour in vivo, as long as it sufficiently simulates relevant gastrointestinal conditions. Therefore, the development of in vitro gastrointestinal systems, which reflects advanced technology and knowledge about the human body, is receiving considerable attention. This article is focused on the biorelevant dynamic apparatuses and their sophisticated design, overcoming many limitations of conventional dissolution devices and allowing a better correlation with in vivo behaviour of solid oral dosage forms.
