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https://doi.org/10.1002/jps.24558
Copy DOIJournal: Journal of Pharmaceutical Sciences | Publication Date: Oct 1, 2015 |
Citations: 25 | License type: publisher-specific-oa |
Phase-sensitive in situ forming implants (ISFI) are a promising platform for the controlled release of therapeutic agents. The simple manufacturing, ease of placement, and diverse payload capacity make these implants an appealing delivery system for a wide range of applications. Tailoring the release profile is paramount for effective treatment of disease. In this study, three innovative formulation modifications were used to control drug release. Specifically, water, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), and bovine serum albumin (BSA) were incorporated into an ISFI solution containing the small molecular weight mock drug, sodium fluorescein. The effects of these additives on drug release, swelling, phase inversion, erosion, and implant microstructure were evaluated. Diagnostic ultrasound was used to monitor changes in swelling and phase inversion over time noninvasively. Water, DiI, and the combination of BSA/DiI functioned to reduce burst release 47.6%, 76.6%, and 59.0%, respectively. Incorporation of water into the casting solution also enhanced the release of drug during the diffusion period of release by 165.2% relative to the excipient free control. Incorporation of BSA into the polymer solution did not significantly alter the burst release (p < 0.05); however, the onset of degradation facilitated release was delayed relative to the excipient-free control by 5 days. This study demonstrates that the use of excipients provides a facile method to tailor the release profile and degradation rate of implants without changing the polymer or solvent used in the implant formulation, providing fine control of drug dissolution during distinct phases of release.
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