Abstract:
Improvement of physicochemical properties of lactose carrier by means of crystal engineering has been reported to increase the deposition of drug in lower airways. α-lactose monohydrate was crystallized either from carbopol gel without strirring or from a constantly-stirred aqueous solution, to obtain lactose crystals designed as carbopol lactose crystals and water lactose crystals, respectively. The carbopol lactose crystals were shown to have a more narrow size distribution than water lactose crystals. The carbopol lactose crystals were tomahawk shape, with higher elongation ratio when compared with the lactose raw material crystals and water lactose crystals. DSC, TGA and FT-IR showed that lactose crystals produced from water or from carbopol gel solution existed as α-lactose monohydrate. The effect of milling on physicochemical characteristics of lactose crystals has been determined. It was shown that milling results in surface change of lactose crystal and a decrease in elongation ratio. As the elongation ratio decreased the flow properties of carbopol lactose crystals was improved. From DSC and XRD studies, it was shown that milling caused a decrease in crystallinity of α-lactose monohydrate. The effect of milling of the lactose crystals on the adhesion forces was investigated. Evaluation of adhesion was carried out by mechanical sieve and tensile strength methods. The results obtained from both methods demonstrated that physical interactions between propranolol hydrochloride or anhydrous theophylline with the lactose raw material crystals were significantly stronger than those with carbopol lactose crystals (p < 0.05). Adhesion force of both drugs was stronger as the milling time was increased. Adhesion force of small size (>150-420 μm) lactose was significantly stronger than that of large size (>420-850 μm) lactose. Additionally, it was shown that adhesion force of anhydrous theophylline was significantly stronger than propranolol hydrochloride for all types of lactose crystals. (p < 0.05).