Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill

Abstract

Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of 8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were successfully printed, as well as combined two-layered 3D tablets, with each of the active substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs from the combined two-layered 3D tablets was observed. The absence of drug-polymer interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further optimization of formulation factors is necessary to achieve complete drug release.

Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.