Spray Drying of Chitosan Acid Salts: Process Development, Scaling Up and Physicochemical Material Characterization.

We investigated a spray drying process for preparing water-soluble salts of high molecular weight chitosan (CH) intended for pharmaceutical excipient applications. CH was derived from chitin of marine lobster origin (Panulirus argus). The effects of organic acid (acetic or lactic acid) and the ratio (difference) of inlet/outlet air temperature (140/90 °C or 160/100 °C) on spray drying were studied. The yield of spray-dried CH salt powders ranged from 50% to 99% in laboratory and industrial-scale processes. The spray-dried dry powder of CH salts consisted of spherical agglomerated particles with an average diameter of 36.2 ± 7.0 µm (CH acetate) and 108.6 ± 11.5 µm (CH lactate). After dispersing the spray-dried CH salt powder samples in purified water, the mean particle sizes obtained for the CH acetate salts were 31.4 nm (batch A001), 33.0 nm (A002) and 44.2 nm (A003), and for the CH lactate salts 100.8 nm (batch L001), 103.2 nm (L002) and 121.8 nm (L003). The optimum process conditions for spray drying were found: an inlet air temperature of 160 ± 5 °C, an outlet temperature of 100 ± 5 °C and an atomizer disk rotational speed of 18,200 min-1. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) results confirmed the amorphous state of the CH salts. The 1H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectra of CH acetate and lactate salts verified that the spray drying process does not affect the polymer backbone. In conclusion, both laboratory and industrial-scale spray drying methods for preparing water-soluble acid salts of CH are reproducible, and the physicochemical properties of the corresponding CH acid salts are uniform.

Stability of spray-dried chitosan salts derived from lobster chitin as a raw material / Estabilidad de las sales de quitosana, obtenidas por secado de aspersión, derivadas de quitina de langosta

Aim. The objective of this work was to develop and validate a method for determining the degree of molar deacetylation of chitosan acetate and chitosan lactate, as well as to study the stability of both salts. Materials and Methods. A spectrophotometric method was validated according to internationally-established quantitative techniques. Three industrial batches of chitosan acetate and chitosan lactate, obtained by spray drying, were stored under shelf life conditions for twelve months. Organoleptic characteristics, the degree of molar deacetylation, pH, loss on drying and microbiological count were determined at the beginning and end of the study. Results and Discussion. The statistical data proved that the two methods complied with international standards for the validation of analytical techniques. It was shown that the procedures developed were linear, specific, precise and accurate, so they can be used for the purposes of quality control and stability study of the polymer salts. Salts remained in powder form, with a light-yellow to dark-yellow coloration. Values of loss on drying (2.5 - 5.2 %) of chitosan salt using acetic or lactic acid, as a solvent, indicated the good quality of spray-dried particles of chitosan. Similar behavior was obtained regarding pH. The two salts stayed within the parameters that determine their quality, both in the initial stage and after twelve months at room temperature. Conclusion: Spray drying chitosan acetate and chitosan lactate, stored at room temperature in a dry place, in double polyethylene bags and multilayer paper bags, kept their physical, chemical and microbiological characteristics for a period of twelve months

Objetivos. Desarrollar y validar un método para la determinación del grado de desacetilación molar del acetato de quitosana y lactato de quitosana, y realizar el estudio de estabilidad de ambas sales. Material y Métodos. Un método espectrofotométrico fue validado según lo establecido internacionalmente para técnicas cuantitativas. Tres lotes industriales de acetato de quitosana y lactato de quitosana, obtenidos mediante secado por aspersión, fueron almacenados bajo condiciones de vida de estante durante doce meses. Se determinaron las características organolépticas, grado de desacetilación molar, pH, pérdida por desecación y el conteo microbiológico al inicio y final del estudio. Resultados y Discusión. El análisis estadístico demostró que ambos métodos cumplieron con los parámetros internacionales establecidos. Se demostró que los procedimientos desarrollados fueron lineales, específicos, precisos y exactos, por lo que pueden ser empleados en el control de calidad y estudio de estabilidad. Las sales se mantuvieron en forma de polvo de coloración amarillo claro u oscura. Los valores de pérdidas por desecación (2,5 - 5,2 %), para el acetato y lactato de quitosana, demuestran la calidad de las partículas de quitosana obtenidas por secado por aspersión. Un comportamiento similar fue obtenido para el pH. Las dos sales mantuvieron los parámetros que determinan su calidad, transcurridos los doce meses a temperatura ambiente. Conclusión: El acetato y el lactato de quitosana, almacenados a temperatura ambiente y en lugares secos, en bolsas dobles de polietileno y sacos de papel multicapas, conservan durante doce meses sus características físicas, químicas y microbiológicas

Effect of molecular weight reduction by gamma irradiation on chitosan film properties.

The present work aimed the influence of molecular weight (MW) reduction by irradiation with (60)Co and polymer concentration on some physical properties of chitosan films. Irradiation of chitosan with a MW of 275.221 kDa and 74.74% of deacetylation degree was performed using a (60)Co source to provide doses of 5, 10, 20 and 50 kGy to obtain chitosans with molecular weights of 247.847, 221.563, 126.469 and 77.063 kDa, respectively. Films were prepared via the solution casting method. Film-forming solutions (FFS) of chitosan irradiated or not, were prepared at 1.5 and 2% (w/v) in a solution of lactic acid at 1% (v/v) and 0.1% (v/v) of Tween 80. The FFS were poured into glass plates of 400 cm(2) and dried at 60 °C during 10h without airflow. The decrease of MW and increase of chitosan concentration increased the tensil strength and water vapor permeability while decreased the elongation at break of the films. The chitosan MW did not significantly influence (p>0.05) the water solubility of films within a same polymer concentration. There was a decrease in the films' brightness with the increase of concentration and a decrease of the MW of irradiated chitosan, while the b* values of films increased and there was an increasing tendency of their apparent opacity.

Safety evaluation of chitosan and chitosan acid salts from Panurilus argus lobster.

Chitosan is a natural polymer with excellent properties such as biocompatibility, biodegradability, non-toxicity and adsorptive abilities. We obtained chitosan derived from Panurilus argus lobster shell and its lactate and acetate salts to introduce in pharmaceutical industry. We examined the single and repeated dose toxicity of chitosan and its lactate and acetate salts. Single oral doses of 2000 mg/kg were well tolerated for all three materials. In the repeat dose tests, animals treated with chitosan only show a slight erythrocytes increase. Variations in erythrocyte and leukocyte count and some biochemical parameters were observed in animals treated with chitosan acid salts. One g/kg orally was found to be the subacute NOAEL for chitosan due to the hematological findings observed were not considered adverse. Chitosans obtained from Panurilus argus lobster shell have low toxicity and may be safe in rats because it did not cause any lethality or changes in the general behavior in both the single and repeated dose toxicity studies.

Effects of spray drying on physicochemical properties of chitosan acid salts.

The effects of spray-drying process and acidic solvent system on physicochemical properties of chitosan salts were investigated. Chitosan used in spray dryings was obtained by deacetylation of chitin from lobster (Panulirus argus) origin. The chitosan acid salts were prepared in a laboratory-scale spray drier, and organic acetic acid, lactic acid, and citric acid were used as solvents in the process. The physicochemical properties of chitosan salts were investigated by means of solid-state CP-MAS (13)C nuclear magnetic resonance (NMR), X-ray powder diffraction (XRPD), differential scanning calorimetry, and Fourier transform infrared spectrometry (FTIR) and near-infrared spectroscopy. The morphology of spray-dried chitosan acid salts showed tendency toward higher sphericity when higher temperatures in a spray-drying process were applied. Analysis by XRPD indicated that all chitosan acid salts studied were amorphous solids. Solid-state (13)C NMR spectra revealed the evidence of the partial conversion of chitosan acetate to chitin and also conversion to acetyl amide form which appears to be dependent on the spray-drying process. The FTIR spectra suggested that the organic acids applied in spray drying may interact with chitosan at the position of amino groups to form chitosan salts. With all three chitosan acid salts, the FTIR bands at 1,597 and 1,615 cm(-1) were diminished suggesting that -NH groups are protonated. The FTIR spectra of all chitosan acid salts exhibited ammonium and carboxylate bands at 1,630 and 1,556 cm(-1), respectively. In conclusion, spray drying is a potential method of preparing acid salts from chitosan obtained by deacetylation of chitin from lobster (P. argus) origin.