title: Effect of co-solvents on the controlled release of calcitonin polypeptide from in situ biodegradable polymer implants.
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 degrees C, but a slower degradation pattern prevailed at 4 degrees and 20 degrees 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.
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, California 91766-1854, USA. sprabhu@westernu.edu
authors.forename: Sunil
authors.initials: S
authors.lastname: Prabhu
authors.forename: Lan P
authors.initials: LP
authors.lastname: Tran
authors.forename: Guru V
authors.initials: GV
authors.lastname: Betageri
mesh_terms: D020341:Absorbable Implants; D001565:Benzoates / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D002116:Calcitonin / Q000737:chemistry*; D015195:Drug Design; D004343:Drug Implants; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D001565:Benzoates; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D012997:Solvents; D019344:Lactic Acid; C033616:poly(lactide); D002116:Calcitonin; D019905:Benzyl Alcohol; C006723:benzyl benzoate