Comparison of the properties of implantable matrices prepared from degradable and non-degradable polymers for bisphosphonate delivery

• Published in: International journal of pharmaceutics 2017-11, Vol.533 (2), p.364-372
• Main Authors: Sovány, Tamás, Csüllög, Anna, Benkő, Ernő, Regdon, Géza, Pintye-Hódi, Klára
• Format: Article
• Language: English
• Subjects: Bone Density Conservation Agents - chemistry; Chitosan; Chitosan - chemistry; Design of experiments; Drug Delivery Systems; Drug Implants; Drug Liberation; Implantable matrix; Near-infrared spectroscopy; Polyvinyl Chloride - chemistry; PVC; Risedronate Sodium - chemistry; Tablets
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.07.023

[Display omitted] The aim of the present study was the development of directly compressed tablets for implantable delivery of risedronate sodium for osteoporosis treatment and the comparison of the mechanism and kinetics of drug release from biogradable (chitosan) and non-degradable (PVC) polymer matrices. The compositions and process parameters were optimized in accordance to a mixed 2 and 3 level full factorial design. Critical Quality Attributes (CQA), such as diametral breaking hardness, porosity and speed of drug dissolution were investigated. The results revealed significant differences between the behaviours of the two polymers. Chitosan exhibited poor compressibility, which resulted in poor mechanical properties and the fast disintegration of chitosan based tablets. Nevertheless, despite the fast disintegration, the chitosan based matrices exhibited one-week-long continuous drug release, which can be due to a strong drug-carrier interaction. The presence of intermolecular hydrogen bonds was confirmed with FT-IR and NIR measurements. In contrast, PVC based compositions exhibited excellent compressibility, good tablet hardness and low porosity. The tablets remained intact during the dissolution and exhibited a slower release rate than what was measured in the case of chitosan based matrices. There was no sign of intermolecular association on NIR spectra, suggesting that the dissolution rate is basically determined by the porosity of tablets, but FT-IR measurements revealed some details of the molecular background of drug release mechanism.