The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients’ specific needs or provide for the localized production of pharmaceutical dosage forms.
Poly (N-vinylcaprolactam) is a polymer that is biocompatible, water-soluble, thermally sensitive, non-toxic, and nonionic. In this study, the preparation of hydrogels based on Poly (N-vinylcaprolactam) with diethylene glycol diacrylate is presented. The N-Vinylcaprolactam-based hydrogels are synthesised by using a photopolymerisation technique using diethylene glycol diacrylate as a crosslinking agent, and Diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide as a photoinitiator. The structure of the polymers is investigated via Attenuated Total Reflectance–Fourier Transform Infrared Spectroscopy. The polymers are further characterised using differential scanning calorimetry and swelling analysis. This study is conducted to determine the characteristics of P (N-vinylcaprolactam) with diethylene glycol diacrylate, including the addition of Vinylacetate or N-Vinylpyrrolidone, and to examine the effects on the phase transition. Although various methods of free-radical polymerisation have synthesised the homopolymer, this is the first study to report the synthesis of Poly (N-vinylcaprolactam) with diethylene glycol diacrylate by using free-radical photopolymerisation, using Diphenyl (2, 4, 6-trimethylbenzoyl) phosphine oxide to initiate the reaction. FTIR analysis shows that the NVCL-based copolymers are successfully polymerised through UV photopolymerisation. DSC analysis indicates that increasing the concentration of crosslinker results in a decrease in the glass transition temperature. Swelling analysis displays that the lower the concentration of crosslinker present in the hydrogel, the quicker the hydrogels reach their maximum swelling ratio.
Previous studies involving poly N-vinylcaprolactam (PNVCL) and itaconic acid (IA) have synthesised the hydrogels with the presence of a solvent and a crosslinker, producing chemically crosslinked hydrogel systems. In this study, however, temperature sensitive PNVCL was physically crosslinked with a pH-sensitive comonomer IA through ultraviolet (UV) free-radical polymerization, without the presence of a solvent, to produce hydrogels with dual sensitivity. The attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy indicated successful polymerisation of the hydrogels. The temperature and pH sensitivity of the hydrogels was investigated. The lower critical solution temperature (LCST) of the gels was determined using the UV spectrometry and it was found that the incorporation of IA decreased the LCST. Rheology was conducted to investigate the mechanical and viscoelastic properties of the hydrogels, with results indicating IA that enhances the mechanical properties of the gels. Swelling studies were carried out at ~20 °C and 37 °C in different buffer solutions simulating the gastrointestinal tract (pH 2.2 and pH 6.8). In acidic conditions, the gels showed gradual increase in swelling while remaining structurally intact. While in basic conditions, the gels had a burst in swelling and began to gradually degrade after 30 min. Results were similar for drug release studies. Acetaminophen was incorporated into the hydrogels. Drug dissolution studies were carried out at 37 °C in pH 2.2 and pH 6.8. It was found that <20% of acetaminophen was released from the gels in pH 2.2, whereas the maximum drug released at pH 6.8 was 74%. Cytotoxicity studies also demonstrated the hydrogels to be highly biocompatible. These results indicate that physically crosslinked P(NVCL-IA) gels possess dual pH and temperature sensitive properties, which may be beneficial for biomedical applications such as drug delivery.