Calcium and Strontium Coordination Polymers as Controlled Delivery Systems of the Anti-Osteoporosis Drug Risedronate and the Augmenting Effect of Solubilizers

Bisphosphonates (BPs) constitute a class of drugs used for the treatment of calcium- and bone-related disorders, including osteoporosis, Paget’s disease, etc. The presence of the anionic phosphonate groups endows them with the ability to act as ligands to metal ions. As a result, the synthesis of complexes or coordination polymers of various structural motifs can be accomplished. In this work, the 3rd generation BP drug risedronate (RIS) was combined with biologically acceptable alkaline earth metal ions (e.g., Ca2+ and Sr2+) in an effort to synthesize new materials. These metal–RIS compounds can operate as controlled delivery systems (CDSs) when exposed to appropriate experimental conditions, such as the low pH of the human stomach. CDS networks containing Ca2+ or Sr2+ and RIS were physicochemically and structurally characterized and were evaluated for their ability to release the free RIS drug during an acid-driven hydrolysis process. Due to the low solubility of RIS at low pH, cationic additives (linear polyethyleneimine and amine-terminated polyaminoamide dendrimer) were utilized as drug solubilizers. Based on the drug release results of this study, there was an attempt to correlate the drug release efficiency with the structural features of these CDSs.