Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.
Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (<6%). The maximum achievable payload was equal to ≈2.5μg/cm(2), which was multifold higher than that achieved had inkjet printing of ciprofloxacin solution been performed. Nevertheless, print substrate with higher liquid uptake capacity is needed to increase the payload nearer to the therapeutic dose. Lastly, the drug release and non-cytotoxicity of the printed nanodrug were successfully established in vitro.
Singapore Institute of Technology, Singapore 138683.
Wean Sin
WS
Cheow
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459.
Tie Yi
TY
Kiew
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459. Electronic address: kunnong@ntu.edu.sg.
Kunn
K
Hadinoto
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D016264:Dextran Sulfate / Q000009:adverse effects / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D065347:Hypromellose Derivatives / Q000009:adverse effects / Q000737:chemistry*; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D057285:Precision Medicine; D066330:Printing, Three-Dimensional; D011786:Quality Control; D012995:Solubility; D013499:Surface Properties; D014783:Viscosity
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005079:Excipients; D020442:Poloxamer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002939:Ciprofloxacin; D016264:Dextran Sulfate; C000595216:polyethylene glycol 8000
Amorphous nanodrug; Individualized dosing; Printable medicine; Printed drug