title: Dilution of semi-solid creams: influence of various production parameters on rheological properties and skin penetration.
abstract: In order to customise treatment for patients, topical formulations are often diluted with drug-free cream bases to adjust the drug dose and thereby the formulations' activity to the patients' needs. However, the process of dilution influences properties of the formulations. Stability can be reduced as well as the microbial stability and most importantly, efficacy and skin penetration behaviour can be severely and unpredictably changed. The present study investigates the effects of production parameters on creams, namely incorporation of an API (active pharmaceutical ingredients) into an OW cream with prior mixing with propylene glycol or without and subsequent automated or manual dilution of the resulting creams with three different cream bases. Effects were measured by influence on microscopic appearance, measurement of chemical stability, skin penetration and rheological behaviour.
  
  
  RESULTS
  suggest strong influence of the cream bases used for dilution of the formulations. Mixture of equal amounts of the employed OW and WO cream proved unfavourable due to inferior penetration behaviour and less appealing microscopic and macroscopic appearance. Prior mixing with PG was of negligible importance for the characteristics of the dilutions, however, the type of API and manner of dilution had an influence on the viscosity of the formulations.
authors.affiliation: University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Nagelreiter
authors.affiliation: University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Kratochvilova
authors.affiliation: University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Althanstraße 14, 1090 Vienna, Austria; University of Vienna, Research Platform 'Characterisation of Drug Delivery Systems on Skin and Investigation of Involved Mechanisms', Vienna, Austria. Electronic address: claudia.valenta@univie.ac.at.
authors.forename: C
authors.initials: C
authors.lastname: Valenta
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004008:Diclofenac / Q000737:chemistry; D004355:Drug Stability; D004917:Erythromycin / Q000737:chemistry; D005438:Fludrocortisone / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D009824:Ointments / Q000737:chemistry* / Q000494:pharmacology*; D019946:Propylene Glycol / Q000737:chemistry; D012212:Rheology; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine; D014867:Water / Q000737:chemistry
chemical_list: D008055:Lipids; D009824:Ointments; D014867:Water; D004008:Diclofenac; D004917:Erythromycin; D019946:Propylene Glycol; D005438:Fludrocortisone
keywords: Chemical stability; Manual mixing; Microscopic characterisation; Rheological characterisation