Predložená práca sa zaoberá vývojom matricovej tablety s predĺženým uvoľňovaním ľahko rozpustného liečiva pramipexolu. Ako polymér riadiaci uvoľňovanie liečiva z vybraných prototypov bol použitý nový excipient Kollidon SR (zmes 80 % polyvinylacetátu a 20 % polyvinylpyrolidónu) a hypromelóza K15M. Testovali sa rôzne koncentrácie polymérov s cieľom dosiahnúť stabilné a pH nezávislé uvoľňovanie pramipexolu 0,26 mg po dobu 24 hodín, vzorky boli pripravené vlhkou granuláciou a lisovaním matricových tabliet. Uvoľňovanie liečiva bolo sledované v disolučných médiách s hodnotami pH od 1,2 až po 6,8 a porovnávané s referenčným prípravkom na báze hydrofilnej matrice s kombináciu troch rôznych polymérov. Požadovaný liberačný profil nízkodávkového liečiva bol dosiahnutý použitím 60,0 hm.% Kollidonu SR vo všetkých médiách a vybraná formulácia F2 vykazovala dostatočnú odolnosť aj voči pôsobeniu etanolu až do koncentrácie 40 obj.%.
The present work deals with the development of a prolonged release matrix tablet of the readily soluble drug pramipexole. The new excipient Kollidon SR (a mix-ture of 80% polyvinyl acetate and 20% polyvinylpyrroli-done) and hypromellose K15M were used as polymers to control drug release from selected prototypes. Various polymer concentrations were tested to achieve a stable and pH independent release of pramipexole of 0.26 mg over 24 hours; samples were prepared by wet granulation and compression of matrix tablets. Drug release was moni-tored in dissolution media with pH values from 1.2 to 6.8 and compared with a reference product based on a hydro-philic matrix with a combination of three different poly-mers. The required release profile of the low-dose drug formulation was achieved using 60.0% (w/w) of Kollidon SR in all dissolution media and the selected formulation F2 demonstrated a sufficient alcohol resistance up to the ethanol concentration of 40% (v/v).
- MeSH
- Administration, Oral MeSH
- Delayed-Action Preparations administration & dosage pharmacokinetics MeSH
- Humans MeSH
- Parkinson Disease drug therapy MeSH
- Polymers MeSH
- Pramipexole * administration & dosage pharmacokinetics MeSH
- Tablets MeSH
- Drug Liberation MeSH
- Drug Development * MeSH
- Check Tag
- Humans MeSH
Prescription opioid abuse is a worldwide growing significant health problem. For that reason, the manufacturing of abuse-deterrent dosage forms is highly important. Alcohol is likely to interact with the drug product and causes a sudden drug liberation (i.e., dose dumping), which possibly results in dangerous side effects and poses a serious safety concern. Thus, it is necessary to develop robust dosage forms that are resistant to the effects of various ethanol concentrations in order to eliminate the risk of immediate release of the entire opioid dose. In this article we review the current information available for drug products and existing formulation strategies that prevent both drug abuse and ethanol-induced dose dumping. These studies may provide insight into how various technologies may differ in their ability to deter opiate drugs abuse.
Tablet matrices are widely used for prolonged release drug delivery. If an alcoholic beverage is ingested simultaneously, the release characteristics of prolonged release formulations can be modified, causing dose dumping which may threaten patient's safety. The presented study deals with the formulation of three different matrices using Methocel K15M, Kollidon SR and Parteck SRP 80, commercially available matrix forming polymers. The influence of hydroalcoholic media on hydration and drug release from the mentioned three types of matrices using tramadol hydrochloride as a model drug substance was investigated. The prepared formulations did not fail in hydroalcoholic media and clearly indicates that matrices produce consistent drug release with no signs of a potential dose dumping. Small differences in drug release profiles were explained in terms of hydration and hydrophilic/hydrophobic interactions between the drug substance and the matrix forming polymers.
- MeSH
- Hypromellose Derivatives MeSH
- Ethanol pharmacokinetics MeSH
- Drug Interactions MeSH
- Humans MeSH
- Analgesics, Opioid * pharmacokinetics MeSH
- Polyvinyl Alcohol MeSH
- Povidone MeSH
- Tablets pharmacokinetics MeSH
- Tramadol * pharmacokinetics MeSH
- Drug Liberation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Publication type
- Meeting Abstract MeSH
- Publication type
- Meeting Abstract MeSH
- Publication type
- Meeting Abstract MeSH
