Functionality related characterization of pretreated wood lignin, cellulose and polyvinylpyrrolidone for pharmaceutical applications
Date
2015-07-07
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Abstract
Ravimvormid koosnevad tavaliselt toimeainest ja erinevatest abiainetest Varasemalt on abiaineid defineeritud, kui ravimi koostisaineid, või ravimi tootmisel kasutavaid aineid, mis sisalduvad ravimis ja millel ei ole mingit toimet organismile. Tänapäeval aga ei saa abiaineid enam pidada inertseteks ja mitteaktiivseteks ravimi koostisosadeks. Abiaine funktsiooniks on luua toimeaine organismi viimiseks sobiv keskkond ja sellega parandada ravimi stabiilsust, lahustuvust/lahustumiskiirust, biosaadavust, välimust või lihtsustada ravimi tootmist.
Tõepoolest, lõpliku ravimvormi omadused ja kvaliteet sõltuvad otseselt abiainete füüsikokeemilistest omadustest. Viimastel aastatel pakub farmaatsiatööstusele suurt huvi uute biomaterjalide süntees ja disainimine abiaineteks, mida oleks võimalik kasutada tablettide koostisosana. Uute abiainete leidmine ja nende väljatöötamine annab hea võimaluse farmaatsiatööstusele ravimpreparaatide/vormide kvaliteedi parandamiseks ja biosaadavuse suurendamiseks. Lignotselluloos ja ligniin on paberitootmise jääkproduktid, mis on kergesti kättesaadavad ja odavad, kuid varasemalt ei ole neid veel abiainetena farmaatsiatööstuses uuritud. Ligniin on üks kolmest (koos tselluloosi ja hemitselluloosiga) polümeersest komponendist, mida võib leida taimede rakuseinas. Kuna lignotselluloos ja ligniin on üsna uued võimalikud abiained, siis nende füsikokeemilistest ja võimalikest tehnoloogiliselt olulistest omadustest on veel vähe teada. Seega oli antud uuringu eesmärgiks analüüsida lignotselluloosi ja ligniini füsikokeemilisi ja funktsionaalsusega seotud omadusi. Biomaterjalide erinevate omaduste uurimiseks valmistasime järgmised ravimvormid: tabletid (mehaaniliselt oluliste omaduste uurimiseks), tahke dispersioon (toimeaine lahustuvuse parendavate omaduste uurimiseks), tablettide katted (ligniini mõju ravimvormi katete mehaaniliste omaduste uurimiseks).
Kokkuvõtteks, ligniini ja lignotselluloosi füsikokeemilised ja funktsionaalsusega seotud omadused näitasid, et antud biomaterjalid sobivad kasutamiseks abiainetena farmaatsias. Samas oli see uuring esimene samm nendele abiainetele rakenduste leidmiseks ja kindlasti on vajalik läbi viia veel lisauuringuid neile sobivaimate funktsioonide leidmiseks.
Medicinal products consist of an active therapeutical ingredient and usually a number of excipients. Excipient is defined as any constituent of a medicinal product that is not an active substance. Today, pharmaceutical excipients can not anymore be considered as inert or inactive compounds. Excipients usually make up the major portion of the pharmaceutical formulation. Thus, excipient physical and chemical property variation is one of the most important input variables that can impact the manufacturing process. Additionally, it is well-known that the properties and performance of the final pharmaceutical dosage form are highly dependent on the physical and chemical properties of the excipients. The design and isolation of new biomaterials for excipients in pharmaceutical systems have created much interest in recent years. Despite of extensive research, however, virtually no new excipient has been introduced past twenty years. Lignocelluloses and lignin are side-products in the paper pulp manufacturing process, and they are readily available and cheap but have not been investigated as excipients in pharmaceutical applications. It was an object of the present PhD research work to investigate the applicability and the functionality related characteristics of pretreated cellulose and lignin as new excipients in pharmaceutical solid dosage manufacturing. The physicochemical and functionality related characteristics of the present biomaterials were investigated in association with (1) direct compression tablets (to study tablet compaction behaviour), (2) oral solid dispersions (to enhance the solubility of poorly water-soluble drugs), and (3) polymeric films intended for solid dosage form coatings (to evaluate the effects of lignification on the mechanical properties of the films). It was found that the physicochemical and functionality-related characteristics of pretreated cellulose and lignin are suitable for using them as excipients in the pharmaceutical formulations. However, the present thesis represents the very first steps on a way of exploring the functionality-related characteristics and applications of new biomaterials. Further studies are needed in order to find out their actual utilization in the pharmaceutical manufacturing processes and final formulations.
Medicinal products consist of an active therapeutical ingredient and usually a number of excipients. Excipient is defined as any constituent of a medicinal product that is not an active substance. Today, pharmaceutical excipients can not anymore be considered as inert or inactive compounds. Excipients usually make up the major portion of the pharmaceutical formulation. Thus, excipient physical and chemical property variation is one of the most important input variables that can impact the manufacturing process. Additionally, it is well-known that the properties and performance of the final pharmaceutical dosage form are highly dependent on the physical and chemical properties of the excipients. The design and isolation of new biomaterials for excipients in pharmaceutical systems have created much interest in recent years. Despite of extensive research, however, virtually no new excipient has been introduced past twenty years. Lignocelluloses and lignin are side-products in the paper pulp manufacturing process, and they are readily available and cheap but have not been investigated as excipients in pharmaceutical applications. It was an object of the present PhD research work to investigate the applicability and the functionality related characteristics of pretreated cellulose and lignin as new excipients in pharmaceutical solid dosage manufacturing. The physicochemical and functionality related characteristics of the present biomaterials were investigated in association with (1) direct compression tablets (to study tablet compaction behaviour), (2) oral solid dispersions (to enhance the solubility of poorly water-soluble drugs), and (3) polymeric films intended for solid dosage form coatings (to evaluate the effects of lignification on the mechanical properties of the films). It was found that the physicochemical and functionality-related characteristics of pretreated cellulose and lignin are suitable for using them as excipients in the pharmaceutical formulations. However, the present thesis represents the very first steps on a way of exploring the functionality-related characteristics and applications of new biomaterials. Further studies are needed in order to find out their actual utilization in the pharmaceutical manufacturing processes and final formulations.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Keywords
farmatseutiline tehnoloogia, ravimvormid, abiained (farm.), stabiilsus, lahustumine, elastsus, pharmaceutical technology, pharmaceutical forms, excipients (pharm.), stability, dissolution, elasticity