Stability Study of Drug-loaded Proteinoid Microsphere Formulations during Freeze-drying

Abstract

Drug-loaded proteinoid microspheres were freeze-dried to facilitate shipping and handling and to enable long term storage. Heparin was chosen as the model drug in developing the optimum lyophilization process. The factors influencing the integrity of either heparin-loaded or unloaded ('empty') proteinoid microspheres during freeze-drying were determined, with emphasis on: selecting an optimum freezing and resuspending temperature; choosing an appropriate cryoprotectant and its optimum concentration in the formulation; and, designing a suitable method for formulating the microspheres. Freezing at/below -70 degrees C was found to minimize damage to the microspheres. Addition of sugars, such as trehalose and lactose, as cryoprotectants, further increased the stability of the heparin-loaded microspheres during freeze-drying. The optimum trehalose or lactose concentrations were determined to be 5% (w/v). Using the optimumized lyophilization process described in this manuscript, microspheres remained intact during freeze-drying. The freeze-dried microspheres were stable for at least three months post-lyophilization.

Effects of preparative parameters on the properties of chitosan hydrogel beads containing Candida rugosa lipase

“…Fresh chitosan beads were rapidly frozen at À80 C, held there for 8 h, then placed ARTICLE IN PRESS on a precooled shelf of the freeze dryer for 14 h. Freezing at or below À80 C was found to minimize damage to biomedical products during freeze drying [21]. In preliminary studies with lipase-loaded chitosan hydrogel beads, freeze drying proved to be better than air drying, oven drying, or ethanol extraction of water in terms of retaining enzyme activity as well as the bead shape and size [22].…”

Stabilization of proteins in solid form

“…This approach is now commonly used in the biopharmaceutical industry, and has facilitated formulation development of many dried therapeutic protein products for human use. The use of disaccharides as stabilizers in drug delivery applications has been relatively limited, but has shown promise [6–10]. …”

Self-assembly of coumarin-conjugated acidic proteinoids

“…Especially, an acidic proteinoid pro tected drug in oral delivery from gastric juice [7,8]. It may give low toxicity to human body because the 1 The article is published in the original.…”