Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold.
Carbamazepine is the first-line anti-epileptic drug for focal seizures and generalized tonic-clonic seizures. Although sustained-release formulations exist, an initial burst of drug release is still present and this results in side effects. Zero-order release formulations reduce fluctuations in serum drug concentrations, thereby reducing side effects. Three-dimensional printing can potentially fabricate zero-order release formulations with complex geometries. 3D printed scaffolds with varying hole positions (side and top/bottom), number of holes (4, 8, and 12), and hole diameters (1, 1.5, and 2 mm) were designed. Dissolution tests and high performance liquid chromatography analysis were conducted. Good correlations in the linear release profiles of all carbamazepine-containing scaffolds with side holes (R(2) of at least 0.91) were observed. Increasing the hole diameters (1, 1.5, and 2 mm) resulted in increased rate of drug release in the scaffolds with 4 holes (0.0048, 0.0065, and 0.0074 mg/min) and 12 holes (0.0021, 0.0050, and 0.0092 mg/min), and the initial amount of carbamazepine released in the scaffolds with 8 holes (0.4348, 0.7246, and 1.0246 mg) and 12 holes (0.1995, 0.8598, and 1.4366 mg). The ultimate goal of this research is to improve the compliance of patients through a dosage form that provides a zero-order drug release profile for anti-epileptic drugs, so as to achieve therapeutic doses and minimize side effects.
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
Seng Han
SH
Lim
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
Samuel Ming Yuan
SM
Chia
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
Lifeng
L
Kang
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore. Electronic address: kevinyap.ehealth@gmail.com.
Kevin Yi-Lwern
KY
Yap
D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients; D010349:Patient Compliance; D066330:Printing, Three-Dimensional; D015203:Reproducibility of Results; D012995:Solubility
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D005079:Excipients; D002220:Carbamazepine
3D printed scaffold; carbamazepine; sustained release; three-dimensional printing; zero-order release