Effect of Co-Solvents on the Controlled Release of Calcitonin Polypeptide fromIn SituBiodegradable Polymer Implants
Open Access
- 1 January 2005
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug Delivery
- Vol. 12 (6), 393-398
- https://doi.org/10.1080/10717540590968873
Abstract
The objective of this study was to design an in situ biodegradable polymer implant controlled-release drug delivery system, using novel combinations of co-solvents and a model polypeptide, calcitonin (CT), and to assess the release of drug as a function of these co-solvents. Formulations were prepared by dissolving/ suspending CT polypeptide in poly-(lactic acid) (PLA) polymer solutions/suspensions containing combinations of a hydrophobic (benzyl benzoate, BB) and a hydrophilic (benzyl alcohol, BA) solvent. The CT-PLA mixtures were each injected into test tubes containing phosphate buffered saline solution to form the in situ implant and sampling was conducted over a 28-day period. The samples were analyzed for drug content using a modified Lowry protein assay procedure. Cumulative drug release demonstrated a rank-order correlation depending on the amount of the hydrophobic (BB) and hydrophilic (BA) solvents within each system. Increasing the amounts of the hydrophobic solvent, BB, in formulations demonstrated a 1.2–4.4-fold increase in CT release. Stability studies of all formulations over a 4-month period showed progressive increase in degradation of the CT polypeptide, especially at 37°C, but a slower degradation pattern prevailed at 4° and 20°C. Differential scanning calorimetric studies revealed a homogenous mixture of drug in the polymer matrix. Overall, these studies demonstrated the feasibility of designing controlled release systems capable of releasing a polypeptide drug as a function of influence of different co-solvent combinations.Keywords
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