Selection of PLA polymers for the development of injectable prilocaine controlled release microparticles: Usefulness of thermal analysis

• Published in: International journal of pharmaceutics 2013-01, Vol.441 (1-2), p.468-475
• Main Authors: Bragagni, Marco, Beneitez, Cristina, Martín, Cristina, de la Ossa, Dolores Hernán Pérez, Mura, Paola Angela, Gil-Alegre, María Esther
• Format: Article
• Language: English
• Subjects: anesthetics; Anesthetics, Local - administration & dosage; Anesthetics, Local - chemistry; Calorimetry, Differential Scanning; Compatibility; Delayed-Action Preparations; differential scanning calorimetry; Drug Carriers - chemistry; Drug Compounding; Drug–polymer miscibility; DSC; Emulsions; encapsulation; Highly water-soluble drug; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; intramuscular injection; intravenous injection; Lactic Acid - chemistry; Local anaesthesia; Microspheres; pain; Pain, Postoperative - drug therapy; Polyesters; polymers; Polymers - chemistry; Prilocaine - administration & dosage; Prilocaine - chemistry; raw materials; Solubility; subcutaneous injection; thermal analysis
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.11.007

The use of injectable local anaesthetics for the treatment of severe postoperative pain is limited by the short duration of the painkilling effect. Pre-formulation studies were carried out for the development of an injectable microparticle formulation for controlled release of prilocaine, an amino-amide type local anaesthetic suitable for intravenous, subcutaneous and intramuscular administration. To the best of our knowledge, the encapsulation of prilocaine into microparticles has not been investigated yet. Three different poly-lactic-acid (PLA) polymers were separately employed for the preparation of the microparticles. Thermal analyses by differential scanning calorimetry (DSC) were carried out for the characterization of the raw materials, to assess the drug–polymer compatibility and miscibility, to investigate the effects of the production process on the components. Empty and prilocaine loaded microparticles were prepared by double emulsion method. All formulations were fully characterized in terms of drug content, morphology, size and in vitro drug release. The preliminary value of PRL solubility in the polymer material determined by DSC was evaluated and discussed as a predictive value for encapsulation efficiency and controlled release. DSC analysis turned out to be a usefulness tool for a fast polymer selection. Microparticles prepared with PLA R202 and R203S showed desirable characteristics for subcutaneous administration and could represent two promising formulations for the development of innovative pharmacological tools in the treatment of postoperative pain.