Preparation and evaluation of a dry elixir for the enhancement of the dissolution rate of poorly water-soluble drugs

Abstract

Various products of microcapsules containing a drug and ethanol in a dextrin wall were prepared using a spray dryer to improve the dissolution rate of poorly water-soluble drugs. Indomethacin (IMC), ketoprofen (KPF) and ibuprofen (IPF) were selected as model compounds. The microcapsules were spherical in shape with a smooth surface and small pieces of broken shells were adhered to large particles regardless of the type of drugs. A cross-sectional view of the dry elixir indicates a large inner cavity containing the ethanolic drug solution in a dextrin shell. The thickness of the dextrin wall (1–3 μm) is sufficient to hold the ethanol solution in the dextrin wall. The geometric mean diameters of L and H microcapsules prepared at low (95°C) and high (140°C) inlet temperatures were about 5.59 and 5.11 μm, respectively. As the ethanol contents increased, the mean diameter of the dry elixir also slightly increased. When the inlet air temperatures (140 vs 95°C) increased, the ethanol contents in the microcapsules decreased due to heat damage, a ballooning effect on the drying droplets and rapid volatilization of ethanol. Ethanol contents were greatest at an inlet air temperature of 90–100°C. The amounts of ethanol in the microcapsules were primarily controlled by the type and concentration of dextrin and inlet air temperature. Ethanol contents in the microcapsules were unchanged during 2 months storage in a sealed glass bottle at 25 ± 1°C. In dissolution studies of microcapsules, the drug dissolution rate within the first 5 min ( k 1) from microcapsules increased dramatically. The k 1 of IPF, KPF and IMC in microcapsules was increased 2-3-, 3-4- and 4-9-fold when compared to drug alone. This result suggests that drugs encapsulated in microcapsules dissolve and disperse quickly as a result of the cosolvent effect of ethanol. However, the amounts of IPF and KPF in microcapsules dissolved for 60 min increased slightly whereas those of IMC were doubled when compared to drug only. The amounts of drugs dissolved from microcapsules were related to the ethanol content in microcapsules. The dissolution of drugs in microcapsules was satisfactorily described by a second-order kinetic process. The second-order dissolution rate constant ( k 2) of drug in microcapsules was much greater than that of drug except for IPF. In the case of IPF, the k 2 of drug in microcapsules decreased appreciably although k 1 was larger compared to drug alone. Microcapsules simultaneously containing ethanol and drug in water-soluble dextrin membranes might be useful to improve the solubility, dissolution rate and bioavailability of poorly water-soluble drugs as a novel dosage form.