Crystallization of progesterone for pulmonary drug delivery.

The purpose of this study is to investigate the suitability of the crystallization process to produce microcrystals of progesterone for respiratory drug delivery. Crystallization of progesterone was carried out from water-isopropanol (IPA) mixture. The antisolvent (water) was added at two different addition rates (10 and 100 mL/min). The mass percentage of antisolvent was varied between (50% and 75%), and the initial drug concentration was adjusted at (0.5 and 1 g/L). The effect of crystallization method (antisolvent precipitation or combined cooling and antisolvent) was also examined. These operating conditions were investigated in a 2(4) factorial design in an effort to optimize the process. Different solid-state and surface characterization techniques were applied in conjunction with measurements of powder flow properties using aerodynamic particle sizer (APS). Powder dispersibility and aerosol performance were analyzed using Anderson Cascade Impactor (ACI). Antisolvent addition rate, initial drug concentration and dynamic solvent composition are shown to have a significant effect on the aerosol characteristics of progesterone microcrystals. An increase of 38.73% in the fine particle fraction (FPF) was demonstrated for some powders produced by combined cooling and antisolvent crystallization. In conclusion, it was possible to control particle size and hence, pulmonary deposition using process parameters alone, and produce particles with a narrow particle size distribution and a mean particle size of 5 microm with nearly no particles larger than 10 microm by direct crystallization. The suitability of deep pulmonary deposition was proved by the platelet-like morphology of processed microcrystals and greater surface-to-volume ratio than spherical particles.

Characterization of ternary complexes of meloxicam-HPbetaCD and PVP or L-arginine prepared by the spray-drying technique.

Ternary complexes of meloxicam (ME) (a poorly water soluble anti-inflammatory drug) with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and either a hydrophilic polymer, namely, polyvinyl pyrrolidone (PVP) or a basic amino acid such as L-arginine, were prepared by the spray-drying technique. The solubilizing efficiency, physical properties and dissolution behaviour of each ternary system of ME-HPbetaCD with either PVP or L-arginine were compared with those of the corresponding binary system of ME-HPbetaCD. Tablets compressed from the ternary system of ME-HPbetaCD-L-arginine were compared with plain and commercial tablets. Phase solubility experiments suggested the formation of an inclusion complex of AL type. Ternary system of ME-HPbetaCD-L-arginine exhibited a stability constant 30.3 times higher than the binary system of ME-HPbetaCD, while the ternary system of ME-HPbetaCD-PVP increased the stability constant 2.2 times only. The prepared complexes were characterized by scanning electron microscopy, differential scanning calorimetry and infra red spectroscopy. Ternary solid complexes indicated the presence of strong interactions between the components. The dissolution behaviour of ME from different ternary complexes was higher than its dissolution from the binary system. Tablets compressed from ternary complexes of ME-HPbetaCD-L-arginine highly improved drug release compared to plain and commercial tablets.

Modulation of a pulsatile release drug delivery system using different swellable/rupturable materials.

Diclofenac sodium tablets consisting of core coated with two layers of swelling and rupturable coatings were prepared and evaluated as a pulsatile drug delivery system. Cores containing the drug were prepared by direct compression using microcrystalline cellulose and Ludipress as hydrophilic excipients with the ratio of 1:1. Cores were then coated sequentially with an inner swelling layer of different swellable materials; either Explotab, Croscarmellose sodium, or Starch RX 1500, and an outer rupturable layer of different levels of ethylcellulose. The effect of the nature of the swelling layer and the level of the rupturable coating on the lag time and the water uptake were investigated. Drug release rate studies were performed using USP paddle method. Results showed the dependence of the lag time and water uptake prior to tablet rupture on the nature of the swelling layer and the coating levels. Explotab showed a significant decrease in the lag time, followed by Croscarmellose sodium and finally by Starch RX 1500. Increasing the level of ethylcellulose coating retarded the diffusion of the release medium to the swelling layer and the rupture of the coat, thus prolonging the lag time.