[The effect of various types of Carbopol and different neutralizing bases on pharmaceutical availability of morphine hydrochloride from hydrogel preparations].
In the second half of the 20th century a heterogenic group of opioid receptors was discovered and identified in the central nervous system and in peripheral tissues. However, micro-type opioid receptors, responsible for analgesic effect of endogenic and egzogenic opioids, were not found on majority of peripheral neurons. They appear in skin or mucous membranes with active inflammatory or neoplastic process due to intensive migration to peripheral nerve efferent fibres. These discoveries made it possible to apply opioid analgesics topically (ointments, hydrogels) on pathologically changed skin or mucous membranes. This study presents the results of tests on two batches of hydrogel preparations produced according to own prescription on the base of acrylic acid polymers (Carbopol Ultrez 10 and Carbopol 980 NF). The polymer carboxyl groups were neutralized with different bases: sodium hydroxide, potasium hydroxide, triethanolamine, sodium tetraborate. The obtained hydrogel preparations were subjected to rheological tests. Extensibility was determined by extensometric method, whereas viscosity, yield stress and thixotropy were determined with the use of cone-plate digital rheometer. The activity of hydrogels hydrogen ions (pH) and the rate of their loss of volatile components at human body temperature were also tested. Using modified Mutimer apparatus morphine hydrochloride (MCl) diffusion was performed from the surface of the produced hydrogels through model stratum corneum (Tomofan) to acceptor fluid (water). The quantity of the released therapeutic agent in time function was determined by spectrophotometric method. The carried out studies have demonstrated that the produced hydrogels are non-Newtonian, viscoelastic, thixotropic systems of similar yield stress. The obtained results do not allow to determine unequivocally the effect of MCl, the kind of Carbopol and cross-linking base on hydrogel viscosity. The inversely proportional dependence between hydrogel viscosity (eta) and theoretical diffusion coefficient (D) of morphine hydrochloride was not observed, either. The loss of volatile components (water) is more effective from hydrogels produced on Carbopol Ultrez 10 base. The process of MCl diffusion is most effective from hydrogel made on Carbopol Ultrez 10 base and neutralized with sodium hydroxide or triethanolamine.
Samczewska
Grazyna
G
Zakad Farmacji Aptecznej, Katedra Farmacji Stosowanej Uniwersytet Medyczny w Łodzi. gsamczewska@o2.pl
D000180:Acrylic Resins; D001682:Biological Availability; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D009020:Morphine / Q000737:chemistry* / Q000493:pharmacokinetics; D011145:Polyvinyls / Q000737:chemistry*; D012212:Rheology
D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D011145:Polyvinyls; C006912:carboxypolymethylene; C097397:morphine methiodide; D009020:Morphine