Spray-dried chitosan as a direct compression tableting excipient.

The objective of this study was to prepare and evaluate a novel spray-dried tableting excipient using a mixture of chitosan and lactose. Three different grades of chitosan (low-, medium-, and high-molecular-weight) were used for this study. Propranolol hydrochloride was used as a model drug. A specific amount of chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g). The resultant solution was sprayed through a laboratory spray drier at 1.4 mL/min. The granules were evaluated for bulk density, tap density, Carr index, particle size distribution, surface morphology, thermal properties, and tableting properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when the granules were prepared using medium- or high-molecular-weight chitosan compared with the low-molecular-weight chitosan. The relative proportion of chitosan also showed a significant effect on the bulk density. The granules prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index (11.1%) indicating the best flow properties among all five formulations. All three granules prepared with 1 g chitosan, irrespective of their molecular weight, showed excellent flow properties. Floating tablets prepared by direct compression of these granules with sodium bicarbonate showed 50% drug release between 30 and 35 min. In conclusion, the spray-dried granules prepared with chitosan and lactose showed excellent flow properties and were suitable for tableting.

Alternate delivery route for amifostine as a radio-/chemo-protecting agent.

Amifostine (ethiofos, WR-2721) is an organic thiophosphate prodrug that serves as an antineoplastic adjunct and cytoprotective agent useful in cancer chemotherapy and radiotherapy. The selective protection of certain tissues of the body is believed to be due to higher alkaline phosphatase activity, higher pH and vascular permeation of normal tissues. Amifostine is conventionally administered intravenously before chemotherapy or radiotherapy. It is approved by the Food and Drug Administration (FDA) to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. It was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer although this indication was withdrawn in 2005. Amifostine is also FDA approved for patients with head and neck cancer to reduce the incidence of moderate to severe xerostomia in patients who are undergoing postoperative radiation treatment where the radiation port includes a substantial portion of the parotid glands. The potential of amifostine as a cytoprotective agent is unlikely to be fully realized if the method of administration is restricted to intravenous administration. Attempts have been made to develop non-invasive methods of delivery such as transdermal patches, pulmonary inhalers, and oral sustained-release microspheres. It is the goal of this article to explore non-intravenous routes of administration associated with better efficacy of the drug. This review will primarily focus on the variety of more recently studied (2002 and later) alternative modes for amifostine administration, including subcutaneous, intrarectal and oral routes.

Engineered nanoparticles in cancer therapy.

Intense research has led to a more comprehensive understanding of cancer at the genetic, molecular, and cellular levels providing an avenue for methods of increasing antitumor efficacy of drugs while reducing systemic side effects. Nanoparticulate technology is of particular use in developing a new generation of more effective cancer therapies capable of overcoming the many biological, biophysical, and biomedical barriers that the body stages against a standard intervention. Nanoparticles show much promise in cancer therapy by selectively gaining access to tumor due to their small size and modifiability. Typically, though not exclusively, nanoparticles are defined as submicroscopic particles between 1 and 100 nm. Nanoparticles are formulated out of a variety of substances and engineered to carry an array of substances in a controlled and targeted manner. Nanoparticles are prepared to take advantage of fundamental cancer morphology and modes of development such as rapid proliferation of cells, antigen expression, and leaky tumor vasculature. In cancer treatment and detection nanoparticles serve many targeted functions in chemotherapy, radiotherapy, immunotherapy, immunodetection, thermotherapy, imaging, photodynamic therapy, and anti-angiogenesis. Not only are modifying agents allowing for greater and more accurate tumor targeting, they are also aiding in the crossing of biophysical barriers such as the blood brain barrier there by reducing peripheral effects and increasing the relative amount of drug reaching in the brain. Moreover, multifunctional nanoparticles perform many of these tasks simultaneously such as targeted delivery of a potent anticancer drug at the same time as an imaging material to visualize the effectiveness of the drug utilized for treatment follow-up. In this review, several recent US and World patents developing and modifying nanoparticles for the detection, analysis, and treatment of cancer are discussed.

Effect of co-solvents on the characteristics of enkephalin microcapsules.

The objective of this project was to study the effect of the presence of co-solvents with dichloromethane on the properties of leu-enkephalin microcapsules. Six co-solvents, including ethyl acetate, methanol, ethanol, acetone, isopropanol and acetonitrile, at three concentrations of 5%, 10% and 20% (v/v), respectively, of dichloromethane were selected for this study. The resulting microcapsules were evaluated for morphology and particle size, surface area, thermal characteristics and efficiency of encapsulation. The analysis of particle size distribution showed bi- and tri-modal distribution of the microcapsules. The median particle size of the microcapsules was between 17 microm and 57 microm. All microcapsules were smaller than 90 microm. Approximately 10% of the microcapsules were smaller than 500 nm. In general, the microcapsules prepared with co-solvents showed relatively smaller median size. The microcapsules were spherical in shape. DSC analysis of the microcapsules showed that there were no significant differences in the glass transition temperatures. There were significant changes in the efficiency of encapsulation due to the addition of co-solvents. Substitution with 20% methanol resulted in 40% increase in the efficiency of encapsulation (12% vs. 17%). Furthermore, substitution with 20% ethyl acetate, isopropanol, or acetonitrile, reduced the efficiency of encapsulation to as low as 6%.