Biphasic burst and sustained transdermal delivery in vivo using an AI-optimized 3D-printed MN patch.
Int J Pharm
; 636: 122647, 2023 Apr 05.
Article
in En
| MEDLINE
| ID: mdl-36754185
ABSTRACT
The objective of the present study was to fabricate microneedles for delivering lipophilic active ingredients (APIs) using digital light processing (DLP) printing technology and quality by design (QbD) supplemented by artificial intelligence (AI) algorithms. In the present study, dissolvable microneedle (MN) patches using ibuprofen (IBU) as a model drug were successfully fabricated with DLP printing technology at â¼ 750 µm height, â¼250 µm base diameter, and tip with radius of curvature (RoC) of â¼ 15 µm. MN patches were comprised of IBU, photoinitiator, Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), polyethylene glycol dimethacrylate (PEGDAMA)550 and distilled water and were developed using the QbD optimization approach. Optimization of print fidelity and needle morphology were achieved using AI implementing a semi-supervised machine learning approach. Mechanical strength tests demonstrated that IBU MNs formed pores both on Parafilm M® and human cadaver skin. IBU-MNs consisting of 0.23 %w/v and 0.49 %w/v LAP with 10 %w/v water showed â¼ 2 mg/cm2 sustained drug permeation at 72 h in skin permeation experiments with flux of â¼ 40 µg/cm2/h. Pharmacokinetic studies in rats displayed biphasic rapid first-order absorption with sustained zero-order input of Ko = 150ug/hr, AUC0-48h = 62812.02 ± 11128.39 ng/ml*h, Tmax = 2.66 ± 1.12 h, and Cmax = 3717.43 ± 782.25 ng/ml (using 0.23 %w/v LAP IBU MN patch). An in vitro in vivo relation (IVIVR) was conducted identifying a polynomial relationship between patch release and fraction absorbed in vivo. This study demonstrates fabrication of dissolvable DLP-printed microneedle patches for lipophilic API delivery with biphasic rapid first-order and sustained zero-order release.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Artificial Intelligence
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Pharm
Year:
2023
Type:
Article
Affiliation country:
United States