Proučevanje možnih interakcij med učinkovinami in derivati mikrokristalne celuloze v zdravilih za zdravljenje srčno-žilnih obolenj z dovoljenjem za uporabo v Republiki Sloveniji

Jeknić, Nina (author), Sollner Dolenc, Marija (mentor)

Srčno-žilna obolenja spadajo med najbolj pogosta obolenja v Republiki Sloveniji. Vzrok za smrt so običajno zapleti koronarne bolezni srca ali bolezni možganskega žilja, ki vodijo v srčni infarkt ali možgansko kap. Srčno-žilna obolenja zdravimo z ustreznimi zdravili, za dober nadzor nad boleznijo pa je zelo pomemben tudi zdrav življenjski slog (zdrava prehrana, telesna aktivnost, izogibanje stresu). V Centralni bazi zdravil smo zasledili 312 zdravil za zdravljenje srčno-žilnih obolenj, ki so odobrena v Republiki Sloveniji in se izdajajo le na recept. ATC klasifikacija deli posamezne skupine naprej še v več podskupin. Največ zdravil je v dveh skupinah: v skupini C09 (zdravila z delovanjem na renin-angiotenzinski sistem) je 151 zdravil, kar predstavlja 48,4 % vseh zdravil, v skupini C10 (zdravila za spreminjanje ravni serumskih lipidov) pa je 63 zdravil, kar predstavlja 20,2 % vseh zdravil. V literaturi so opisane možne interakcije med nekaterimi zdravilnimi učinkovinami, ki jih najdemo v teh zdravilih (enalaprilijev maleat, izosorbidmononitrat) ter mikrokristalno celulozo (MCC) in njenimi derivati. Na podlagi teh informacij smo se lotili ugotavljanja pogostnosti pojavljanja MCC in njenih derivatov v izbranih zdravilih. Najbolj pogosto smo v zdravilih zasledili mikrokristalno celulozo (v 213 zdravilih oz. 68,3 % zdravil), v 43,3 % zdravil smo zasledili hidroksipropilmetilcelulozo (HPMC), v 15,1 % zdravil hidroksipropil celulozo (HPC), etilcelulozo (EC) smo zasledili samo v dveh zdravilih (0,6 % vseh zdravil), metilceluloze (MC) pa v nobenem. V 56 zdravilih (17,9 % vseh zdravil) nismo zasledili MCC in njenih izbranih derivatov MC, EC, HPC in HPMC. Po pregledu sestave izbranih zdravil in iskanju možnih interkacij med zdravilnimi učinkovinami in pomožnimi snovmi v literaturi, smo možnost le-teh zasledili le v zdravilih, ki so vsebovala enalaprilijev maleat ali izosorbidmononitrat v kombinaciji z MCC. Možnost za neželene interakcije predstavljajo tudi soli zdravilnih učinkovin, katerih nasprotni ioni (npr. kloridni, mezilatni in bezilatni anion) potencialno lahko vstopijo v kemijsko interakcijo s HPC ali HPMC in tvorijo genotoksične prodtukte. Po pregledu literature lahko sklepamo, da so zdravilne učinkovine za zdravljenje bolezni srca in ožilja v veliki večini primerov kompatibilne z MCC in izbranimi derivati MC, EC, HPC in HPMC.

• Language: Slovenian
• Keywords: neželene interakcije, mikrokristalna celuloza, hidroksipropilmetilceluloza, hidroksiproipilceluloza, etilceluloza, zdravila za zdravljenje srčno-žilnih obolenj
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-125050
• Publication date in RUL: 03.03.2021

Secondary language

• Language: English
• Title: A study of possible interactions between active ingredients and microcrystalline cellulose derivatives in medicines used for treatment of cardiovascular diseases authorized in the Republic of Slovenia

Abstract

Cardiovascular diseases are among the most common diseases in the Republic of Slovenia. The causes of death are usually complications of coronary heart disease or cerebrovascular disease, leading to a heart attack or stroke. Cardiovascular diseases have to be treated with appropriate medications but a healthy lifestyle is also very important for good control of the disease (eg. healthy diet, physical activity, stress avoidance). In the Central Database of Medicinal roducts, we found 312 medicinal products that are approved in the Republic of Slovenia and are issued only on prescription. The ATC classification divides individual groups into several subgroups in advance. Most drugs are in two groups: in group C09 (agents acting on the renin-angiotensin system) there are 151 drugs, which represents 48.4 % of all drugs, and in group C10 (lipid modifying agents) there are 63 drugs, which represents 20.2 % of all drugs. Literature describes possible interactions between some of the active substances found in these medicines (enalapril maleate, isosorbide mononitrate) and MCC and its derivatives. Based on this information, we set out to determine the frequency of occurrence of MCC and its derivatives in selected drugs. MCC was most often found in medicines (in 213 medicines or 68.3 % of medicines), HPMC was found in 43.3 % of medicines, HPC in 15.1 % of medicines, EC was found in only two medicines (0.6 % of all medicines) and MC was not found in any of them. MCC and its selected derivatives MC, EC, HPC and HPMC were not found in 56 medicines (17.9 % of all medicines). After reviewing the composition of the selected medicines and searching for possible interactions between active pharmaceutical ingredients and excipients in literature, the possibility of these interactions was observed only in medicines containing enalapril malate or isosorbide mononitrate in combination with MCC. Drug-excipient chemical interactions could also be possible in medicines containing drug salts whose opposing ions (e.g. chloride, mesylate and bezyl anion) could potentially interact with HPC or HPMC and form genotoxic products. After reviewing the literature, it can be concluded that drugs for the treatment of cardiovascular disease are in the vast majority of cases compatible with MCC and selected derivatives MC, EC, HPC and HPMC.

• Keywords: drug-excipient interactions, microcrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, medicines for the treatment of cardiovascular diseases