Natural polysaccharides platforms for oral controlled release of ketoprofen lysine salt

Abstract

Context: Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1–2 h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity.

Objective: In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release.

Materials and methods: Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment.

Results and discussion: Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DR^®caps) a delivery platform has been developed to control KL release in a delayed (90 min lag time) and prolonged way (270 min complete release).

Conclusion: The platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.

Keywords:

• Ketoprofen lysine salt
• oral controlled release platforms
• polysaccharides based beads
• prilling
• xerogel

Disclosure statement

The authors declare that they have no conflicts of interest to disclose.

Funding information

This work was supported by PON R&S 2007–2013 codex PON02_00029_3203241 (POLIFARMA) as part of the research project “Progettazione e Sviluppo di Sistemi Terapeutici per il Rilascio Controllato di Famaci Attivi nelle Early Morning Pathologies” and authors would like to thank MIUR (Ministero dell'Istruzione, dell'Università e della Ricerca) for the provided financial support.