Polyelectrolyte-drug materials for nasal and pulmonary administrations obtained by spray-drying: A review.

CESCHAN NE; MANZO RH; PIÑA J; BUCALÁ V; RAMÍREZ RIGO MV

Rosario

Congreso; II RICIFA; 2012

Universidad Nacional de Rosario

Introduction The acid-base interaction between polyelectrolytes (PE) and ionizable drugs (D) may modify stability, solubility, dissolution or permeation of therapeutic agents. This strategy is a valuable resource to improve drug bioavailability or reduce side effects.(1) The PE-D complexes can be obtained in solution, dispersion or in solid state.(2) Regarding particulate systems solids forms, the design of powders with controlled properties (e.g., respirable particles) is a research area of high activity and importance.(3) Particularly, nasal and pulmonary administrations are receiving great attention as non-invasive drug delivery routes. However, the performance of the delivery system relies on, among other aspects, inhaler design, air flow generated by the patient and the powder formulation and properties. The powder properties (such as size, shape, specific surface area, density and crystallinity) can be adjusted by selecting adequate formulations, processes and operating conditions.(4) Spray-drying is an interesting option because it is a simple, continuous and scalable technique.(5) In this context, the aim of this work is to review scientific reports in order to determine the potentiality of obtaining particles of PE-D complexes by spray-drying for nasal and pulmonary administrations and to highlight the main achievements and challenges in the area. Materials and methods The information was recovered from scientific data bases using spray-drying, nasal/pulmonar administration and PE-D complexes as keywords. Results Twelve research articles or reviews meeting the search criteria were found. The analyzed information is described below: Materials: New materials combining PE with oppositely charged D or interpolyelectrolyte complexes with D that neutralize residual charges were reported. In particular, cationic PE (chitosan, polylysine, and cationic dendrimers) were studied as carriers of DNA, plasmids, oligonucleotides, zolmitriptan. On the other hand, anionic PE (dextran, alginic acid and poly(ε-caprolactone)) were associated with fluoroquinolones, rifampicin, isoniazid, perphenazine or peptides and proteins with positive charges. The reported interpolyelectrolyte-drug complexes were constituted by chitosan-alginic acid-fluoroquinolones or alginic acid-polylysine-oligonucleotides associations. Uses: Particulate systems were designed for nasal and pulmonary administrations to treat local and systemic infections, migraine, among others diseases and also for gene therapy. Particles properties: The reported particles were rounded or nearly rounded, dense, relatively monodisperse and had aerodynamic diameters smaller than 6µm. Ionic interaction between the components of the material was confirmed. Advantages of new materials: The PE-D particles were found to be carriers that can target the bioactive molecule to the action or absorption sites and can modify properties such as: compaction and transfection of DNA, bioadherence and mucociliary clearance of particles, stability, dissolution and permeability of drugs. The studies allow concluding that, the drugs bioavailability can be improved. Operating conditions: The effect of the processing variables on particles size was studied. The operating conditions that most affected the powder size were: inlet air temperature and feed and atomization air volumetric flowrates. The feed viscosity and solids concentration were also found relevant. The following unexplored aspects emerged from the performed review: a) combinations of PE and D with bioavailability problems or side effects (b-adrenoceptor blocking agents, opioid analgesics, other antibiotics, antihistamines, NSAIDs); b) detailed characterization of the solid state; c) global analysis about the influence of the atomized solution or suspension composition and the operating conditions on particles properties (e.g., shape, specific surface area, density and crystallinity) and; d) process optimizations in order to improve or tune specific properties of the powders. Conclusion The preparation of PE-D complexes by spray-drying is feasible. The obtained products combined the attractive characteristics of complexes and inhalable particles. The design of new powders focusing on the relationship between the product quality and feed formulation/operating conditions becomes an important challenge.