Polyoxyethylene fatty acid esters as potential promotors of transdermal absorption for morphine hydrochloride and sulphate.
The presence of opioid receptors mu in pathologically changed skin and mucosa justifies application of preparations with morphine salts to obtain topical analgesic activity. Numerous factors associated with the vehicle and therapeutic agent physiochemical properties affect the capability and rate of penetration of a therapeutic substance in the form of a drug into dermis. Promotors of transcutaneous absorption, which weaken the integrity of epidermal corneal layer and thus, increase therapeutic substance penetration play more and more important role. In this study non-ionic macromolecular surface active compounds from Rokacets group were suggested as potential promotors of transdermal absorption for morphine sulphate and hydrochloride. The aim of the study was to work out prescription composition of ointment with morphine salts of optimal rheological and morphological parameters and high pharmaceutical availability of the therapeutic agent (morphine sulphate, hydrochloride). Three model emulsive ointment vehicles were prepared and selected promoters of transdermal absorption were introduced into them. On the basis of the formed vehicles ointments were made with morphine sulphate and hydrochloride. The obtained vehicles and ointment preparations were subjected to rheological tests. Spreadness was determined by extensometric method and viscosity with digital cone-plate rheometer. Morphological parameters of the vehicles and ointments, such as: pH and pharmacopeal density were estimated. Carrying out direct diffusion from the surface of the preparation to acceptor fluid (to water), the amount of the released therapeutic substance in time function was determined by spectrophotometric method. The performed tests demonstrated that the investigated vehicles and ointments are non-Newtonian systems, viscoelastic and highly thixotropic. The kind of morphine salt affects the spreadness and viscosity of model ointments. Preparations with morphine hydrochloride have higher spreadness than viscosity and more alkaline pH. From among the investigated non-ionic surface active compounds Rokacet R-40 appeared to be the most beneficial promotor of transdermal absorption for both pharmacopeal morphine salts. Pharmaceutical availability of morphine sulphate and hydrochloride is the highest from ointments with its content in the vehicle prescription.
Samczewska
Grazyna
G
Katedra Farmacji Stosowanej, Uniwersytetu Medycznego w Lodzi.
Piechota-Urbańska
Magdalena
M
Kołodziejska
Justyna
J
D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D009824:Ointments / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D012212:Rheology / Q000145:classification; D012869:Skin Absorption / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D014783:Viscosity
D000701:Analgesics, Opioid; D005227:Fatty Acids; D009824:Ointments; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D009020:Morphine