| Abstract | CILJ ISTRAŽIVANJA Izrada magistralnih i galenskih pripravaka u ljekarničkom laboratoriju još uvijek predstavlja najpogodniju, u pojedinim slučajevima i jedinu, terapijsku opciju za pacijenta kad ne postoji industrijski lijek ili je potrebna priprema pogodnog terapijskog oblika ili doze individualno prema potrebi pacijenta. Magistralni i galenski pripravci ne prolaze strogu završnu kontrolu kvalitete kao industrijski lijekovi, a ljekarnik je u potpunosti odgovoran za kvalitetu farmaceutskih supstancija, izradu pripravaka te njihovo pravilno označavanje i izdavanje. Cilj specijalističkog rada je dati pregled regulative i smjernica o izradi magistralnih i galenskih pripravaka, obrazložiti važnost ulazne kontrole farmaceutskih supstancija (potvrde identiteta) koje se koriste za izradu pripravaka, prikazati analizu tri farmaceutske supstancije NIR spektroskopijom i objasniti njezine prednosti u potvrdi identiteta farmaceutskih supstancija te dati poticaj podizanju svijesti o potrebi uspostavljanja sustava kvalitete u ljekarničkom laboratoriju kao i podizanju kvalitete i sigurnosti izrade magistralnih i galenskih pripravaka.
MATERIJALI I METODE Istraživanja u svrhu izrade rada uključuju pregled dostupne znanstvene literature o NIR tehnici i njenoj primjeni u analitici lijekova općenito, trenutnih studija, smjernica i zakonskih regulativa vezano uz izradu i kontrolu kvalitete magistralnih i galenskih pripravaka te ulaznu potvrdu identiteta farmaceutskih supstancija.
Specijalistički rad je eksperimentalnog karaktera. U praktičnom dijelu rada korištene farmaceutske supstancije za analizu NIR spektroskopijom (eritromicin, glicerol, bijeli vazelin) su zadovoljavajućih zahtjeva kvalitete u skladu s monografijama Europske farmakopeje. Analizirane su na uređaju Apo-Ident 2 NIR spektrometru prilagođenom potvrdi identiteta supstancija u ljekarništvu. Apo-Ident 2 u svom programu QuickStep sadrži referentne NIR spektre najčešćih supstancija korištenih u izradi pripravaka u ljekarnama. Potvrda identiteta bijelog vazelina provedena je dodatno i kemijskom
reakcijom prema monografiji Hrvatske farmakopeje usklađenoj s Europskom farmakopejom. Analize su provedene u ljekarničkom laboratoriju ZU Ljekarna Marušić, u prostoriji za analize u uvjetima reguliranog tlaka, temperature i izmjene zraka.
REZULTATI Rezultati analize tri farmaceutske supstancije prikazani su u obliku NIR spektara, uz objašnjenje načela NIR tehnike i načina interpretacije rezultata mjerenja. Prikazan je rezultat i kemijske reakcije potvrde identiteta bijelog vazelina. Navode se prednosti NIR tehnike u svrhu potvrde identiteta pred nepouzdanim i nedovoljno selektivnim kemijskim reakcijama potvrde identiteta, uključujući jednostavnu i brzu analizu bez obrade uzorka koji se ne uništava mjerenjem te se dalje može koristiti u izradama pripravaka. NIR tehnika ne zahtijeva upotrebu standarda jer se identitet potvrđuje usporedbom NIR spektra ispitivane supstancije s referentnim spektrom iz baze podataka. Prikazano je kako je koncipiran sustav osiguranja kvalitete u ZU Ljekarni Marušić, zašto je važno slijediti propisane standardne operativne postupke, čuvati obaveznu dokumentaciju sirovina (certifikate analize) i analitička izvješća ulazne analize farmaceutskih supstancija. ZAKLJUČAK Magistralni i galenski pripravci još uvijek predstavljaju jedinu terapijsku opciju kada ne postoji industrijski lijek prikladnog oblika, doze, punila i slično. Ljekarnik je u potpunosti odgovoran za nabavu farmaceutskih supstancija, njihovu ulaznu analizu (potvrdu identiteta), izradu pripravaka prema smjernicama struke te pravilno izdavanje. NIR tehnika omogućava brzu i jednostavnu provjeru identiteta supstancija u tekućem, čvrstom i polučvrstom stanju, bez obrade uzorka, pripreme reagensa ili gubitaka analizirane supstancije. Potvrda identiteta u ZU Ljekarni Marušić uređajem Apo-Ident 2 NIR spektrometrom predstavlja vrlo jednostavnu, brzu i egzaktnu opciju, koja osigurava da pacijentima budu izdani sigurni i kvalitetni magistralni pripravci. |
| Abstract (english) | OBJECTIVES Compounding of magistral and galenic preparations in compounding laboratory in pharmacy in some cases is still most suitable and only therapeutic option for patient when industrial (registered) drug is unavailable or doesn't exist on the market, or is necessary to prepare specific pharmaceutical form, or adjust therapeutic doses individually depending on patient's needs. Compounded magistral and galenic preparations are not subjected to strict final quality control testing as industrial drugs, and pharmacist is completely responsible for quality of pharmaceutical substances, compounding process, and proper labeling and dispensing of compounded preparations. The aim of this paper is to give insight in regulations and guidelines of compounding of magistral and galenic preparations, explain importance of entry quality control of pharmaceutical substances (identity confirmation) used in compounding of preparations, show results of analyses of three pharmaceutical substances analyzed with NIR spectroscopy, explain advantages of NIR spectroscopy in identity confirmation of pharmaceutical substances, raise awareness of need of quality management system in compounding laboratory in pharmacy, also putting quality and safety of compounded preparations on higher level.
MATERIALS AND METHODS Research for purpose of creating this paper includes review of available scientific literature about NIR technique and its application in analysis of drugs, current studies, guidelines and legal regulations about magistral and galenic preparations and entry identity confirmation of pharmaceutical substances.
This paper has experimental nature. In practical part of the paper, pharmaceutical substances (erythromycin, glycerol and white vaseline) used for analysis by NIR spectroscopy, meet the quality requirements according to monographs of European pharmacopoeia. They were analyzed on the
Apo-Ident 2 NIR spectrometer device adapted to confirm the identity of substances in pharmacy. Apo-Ident 2 in its QuickStep program contains the reference NIR spectrums of the most common substances used in compounding of preparations in pharmacies. Identity confirmation of white vaseline was additionally carried out by a chemical reaction according to the monograph of the Croatian Pharmacopoeia harmonized with the European Pharmacopoeia. The analyses were performed in the pharmacy laboratory of ZU Ljekarna Marušid, in the analysis room under conditions of regulated pressure, temperature and air exchange.
RESULTS The results of the analysis of three pharmaceutical substances are presented in the form of NIR spectrums, with an explanation of the principles of NIR technique and how to interpret the measurement results. The result of the chemical reaction of identity confirmation of white vaseline is also shown. The advantages of the NIR technique for the purpose of identity confirmation over unreliable and insufficiently selective chemical identity confirmation reactions are listed, including simple and fast analysis without sample processing that is not destroyed by measurement and can further be used in compounding of preparations. The NIR technique does not require the use of standards because the identity is confirmed by comparing the NIR spectrum of the tested substance with a reference spectrum from the database. The concept of quality assurance system at ZU Ljekarna Marušid is shown, also stated why it is important to follow the prescribed standard operating procedures, to keep the mandatory documentation of raw materials (certificates of analysis) and analytical reports of entry analysis of pharmaceutical substances.
CONCLUSION
Magistral and galenic preparations are still the only therapeutic option when there is no industrial drug of suitable form, dose, excipient and so on. The pharmacist is fully responsible for the purchase of pharmaceutical substances, their entry analysis (identity confirmation), compounding of
preparations according to professional guidelines, and proper dispensing. NIR technique enables a quick and simple identity confirmation of a substance in liquid, solid and semi-solid form, without sample processing, preparation of reagents or losses of the analyzed substance. Identity confirmation at ZU Ljekarna Marušid with the Apo-Ident 2 NIR spectrometer is very simple, fast and exact option, which ensures that safe and high-quality preparations are dispensed to patients. |
