Pain is experienced by a majority of cancer patients. As life expectancy has increased in developed and developing countries, cancer-related pain has become a major health concern. Despite the use of the three-step analgesic ladder proposed by the World Health Organization, pain still remains under treated. Morphine, the gold standard against which all other opioids has been compared is considered the first choice for management of cancer-related pain. However, recently focus has shifted to the use of hydromorphone, a semi-synthetic derivative of morphine, which is more potent, more soluble and has a comparable side-effect profile. This review focuses on the use of hydromorphone for the management of cancer-related pain emphasizing on the various routes of administration as well as dosage forms, and providing a direction for the preference of a particular route depending on the need for a rapid effect and the individual's situation. Various approaches used to modify the release of hydromorphone from the drug delivery systems with the perspective of improving patient compliance are also being discussed.
The feasibility of delivering hydromorphone by transdermal iontophoresis to obtain therapeutically effective analgesic concentrations for the management of cancer-related pain was evaluated. Anodal iontophoresis was performed, and the effect of current strength, current duration, solution pH, presence of buffer ions, and drug concentration on the transdermal permeation of hydromorphone was investigated in vitro. Freshly excised full-thickness hairless rat skin and side-by-side permeation cells connected to the Phoresor II with Ag/AgCl electrodes was used. The flux of hydromorphone was observed to significantly increase (P < 0.05) from 72.04-280.30 microg/cm(2)/h with increase in current strength from 0.10-0.50 mA. A linear relationship was obtained between hydromorphone flux and current strength. Furthermore, the flux of hydromorphone was influenced by solution pH and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone was observed to significantly increase (P < 0.05) with a 10-fold increase in hydromorphone hydrochloride concentration from 0.01-0.10 M. However, with further increase to 0.50 M, there was no significant difference in flux. These results show that by manipulating electronic and formulation variables, the transdermal iontophoretic delivery of hydromorphone can be controlled, and therapeutically effective concentrations of hydromorphone for the management of cancer-related pain can be obtained.
Transdermal iontophoresis, a noninvasive technique that facilitates drug transport through the skin by the use of an external electrical field, has expanded the scope of drugs that can be delivered transdermally and enables programmable drug delivery. In general, transdermal iontophoresis is considered to be a safe procedure, associated with moderate erythema and tingling sensations. However, ensuring that the skin barrier maintains its integrity during iontophoresis is an essential factor to increase its clinical applicability. This review focuses on the effect of transdermal iontophoresis on the integrity of skin, as evaluated by impedance spectroscopy, microscopy, differential scanning calorimetry, infrared spectroscopy, X-ray diffraction, transepidermal water loss, laser doppler velocimetry, visual scoring, chromameter readings, and patient evaluation studies.
Hydromorphone, a semi-synthetic derivative of morphine, is being used in the treatment of moderate to severe cancer-related and post-operative pain. It is also one of the most commonly prescribed drug that is often abused. Hence, its detection in biological samples and tissues is important for legal and therapeutic reasons. The purpose of this review is to give a brief description of the various non-chromatographic and chromatographic analytical techniques, namely immunoassays, thin layer chromatography, high performance liquid chromatography, liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and capillary electrochromatography, that have been used by analysts to assay hydromorphone from the early 1970s to present. This review aims to help the analytical community make efficient choices between various analytical methodologies based on concrete parameters of reliability, sensitivity, specificity, precision, accuracy, cost and potential for automation.
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