Application Of Selective Laser Sintering Technology In Oral Solid Preparations

Selective laser sintering(Selective Laser Sintering,SLS)selectively sinter the powder layer by layer with a laser beam to prepare 3D printlets.Up to now,SLS technique has been widely used in the field of tissue engineering and personalized implants.However,the formability and functionality of pharmaceutical materials during laser sintering is still lack of systematic study,which limits the application of SLS technique in the field of oral preparations.The SLS printability of common drugs and excipients was systematically studied in this article.And the influence of formulation,process parameters and model design on the appearance and dissolution of printlets was investigated.The results could provide an experimental basis for SLS printing personalized oral preparations.With different laser powers,single layer of circle sample was printed on a pure drug powder bed.The SLS printability of different drugs was evaluated by observing the appearance of the printed circles.The results showed that yellow drugs could be directly sintered and had SLS formability.Nifedipine had printability at a lower power of 0.5 W.White drugs could be sintered by adding photoabsorber.Ibuprofen(IBU)and metoprolol tartrate(MT)had SLS printability at a lower laser power(0.75 W).The melting temperature range of drugs affected their SLS printability.Using MT as typical drug,circular and triangular were printed based on SLS.The center thickness of printed circle and warpage height at the edge were measured to evaluate the printing efficiency and accuracy,respectively.The arc length of external corner and the inner cavity area of the printed triangle were determined to evaluate the printing accuracy.The results showed that when 0.1%tartrazine lake was used as photoabsorber,the printed circular had the highest printing accuracy.Within the range of SLS printability,increasing the laser power or reducing the scanning speed facilitated the printing efficiency of MT powder but adversed to its printing accuracy.At the optimized laser power(1.0 W)and scanning speed(2.5 mm/s),both the printing accuracy of circular and the triangular sample were the highest.With different laser powers,single layer of circle sample was printed on powder bed containing different pharmaceutical polymers.The SLS printability of common immediate-release or sustained-release polymers was evaluated by observing the appearance of the printed circles.It was found that non-crystalline polymers such as polyvinyl alcohol(PVA)and Eudragit~?RL(RL)had good SLS printability at the laser power range of 1.5-3.5 W,and the printing mechanism was powder sintering.In contrast,crystalline polymers such as polyethylene glycol(PEG)and stearic acid were also printable showing obvious edge warpage,and the printing mechanism was powder melting.The thermal operating temperature range of polymers affected their SLS printability.Using RL as typical polymer,circular was printed based on SLS.It was found that when 0.2%tartrazine lake was used as photoabsorber,the printed circular had the best printing efficiency and accuracy.Using PEG and PVA as typical immediate-release polymers,RL and hydroxypropyl methylcellulose(HPMC)as typical sustained-release polymers,circular and triangular were printed based on SLS.The center thickness of printed circle and warpage height at the edge were measured to evaluate the printing efficiency and accuracy,respectively.The arc length of external corner and the inner cavity area of the printed triangle were determined to evaluate the printing accuracy.Within the range of SLS printability,increasing the laser power or reducing the scanning speed facilitated the printing efficiency but was adverse to the printing accuracy.Considering the printing accuracy,the optimized laser power of these polymers was 1.0 W;and the optimized scanning speeds were:PEG(3.0 mm/s)>PVA and RL(2.0 mm/s)>HPMC(1.75 mm/s).Using grid and shell models,insoluble drug IBU was directly printed to be immediate-release tablets and the drug immediate-release behavior was evaluated.It was found that grid tablets with smaller internal fill density had faster drug dissolution,due to the smaller the specific surface area.Shell tablets with higher side thickness had faster drug dissolution,due to the less sintered powder.Using shell model,the effect of additives on the immediate-release behavior was evaluated.It was found that when 10%sodium carboxymethyl starch was added,the immediate-release tablets had good printability,and the drug released within 3 min was completed(97.2%).This optimized formulation could be used to print various personalized immediate-release preparations,all of which had a good appearance and completely released within 5 min.Besides,the stability of IBU during the SLS printing process was evaluated by drug content determination and infrared spectroscopy analysis.And whether the crystal of IBU was changed during SLS printing was evaluated by DSC and XRD analysis.It was found that the drug content of printed tablets was(99.9±3.2)%,and no difference was observed in the infrared spectrum.The results indicated that IBU was chemical stable during printing.Besides,the DSC and XRD curves also proved that IBU crystal form kept the same during printing.With RL and HPMC as polymers,MT sustained-release tablets were printed using matrix,multiple-layers,and reservoir models to evaluate the sustained-release property.It was found that both matrix tablets and reservoir tablets have sustained-release property within 12 hr.When the coating thickness at the side was 3.5 mm and the HPMC concentration in the coating was 25%,the printed tablets had the best 12 hr sustained-release behavior:the drug released was 42.8%within 4 hr and 92.1%within12 hr.The corrosion behavior of optimized sustained-release tablets was studied,and the dissolution curve was fitted by different equations.The drug release mechanism was erosion(n>0.89).