Microwave Synthesis of Nanostructured Functionalized Polylactic Acid (nfPLA) for Incorporation Into a Drug Crystals to Enhance Their Dissolution
Document Type
Article
Publication Date
8-1-2023
Abstract
Active pharmaceutical ingredients that have low aqueous solubility pose a challenge in the field of drug delivery. In this paper we report for the first time the synthesis of nano-structured, hydrophilized polylactic acid (nfPLA) and its application in the delivery of low solubility drugs. Microwave induced acid oxidation was used to generate nfPLA where the oxygen concentration increased from 27.0 percent to 41.0 percent. Also, the original non dispersible PLA was converted to a relatively dispersible form with an average particle size of 131.4 nm and a zeta potential of -23.3 mV. Small quantities of the nfPLA were incorporated into the crystals (0.5 to 2.0 % by weight) of a highly hydrophobic, low solubility antifungal drug Griseofulvin (GF) to form a composite (GF-nfPLA). An antisolvent approach was used for the synthesis of the drug composite. SEM and Raman imaging showed non-uniform distribution of the nfPLA on the crystal surface. The solubility of GF increased from 8.89 µg/mL to as high as 49.67 µg/mL for the GF-nfPLA. At the same time zeta potential changed from -15.4 mV to -39.0 mV, therefore the latter was a relatively stable colloid. Octanol-water partitioning also showed a similar effect as logP reduced from 2.16 for pure GF to 0.55 for GF-nfPLA. In vitro dissolution testing showed six times higher aqueous solubility of GF-nfPLA compared to pure GF. The time for 50 (T50) and 80 % (T80) dissolution reduced significantly for the nfPLA composites; T50 reduced from 40.0 to 14.0 min and T80 reduced form unachievable to 47.0 min. Overall, the PLA which is an FDA approved, bioabsorbable polymer can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower the required dosage for drugs.
Identifier
85151345581 (Scopus)
Publication Title
Journal of Pharmaceutical Sciences
External Full Text Location
https://doi.org/10.1016/j.xphs.2023.03.011
e-ISSN
15206017
ISSN
00223549
PubMed ID
36958690
First Page
2260
Last Page
2266
Issue
8
Volume
112
Recommended Citation
Islam, Mohammad Saiful and Mitra, Somenath, "Microwave Synthesis of Nanostructured Functionalized Polylactic Acid (nfPLA) for Incorporation Into a Drug Crystals to Enhance Their Dissolution" (2023). Faculty Publications. 1529.
https://digitalcommons.njit.edu/fac_pubs/1529