title: Evaluation of creams and ointments as suitable formulations for peldesine.
abstract: In-vitro studies were conducted to study the efficacy of mixed and self-emulsifying creams and hydrophobic ointment formulations in delivering peldesine (BCX-34) into and across cryopreserved human cadaver skin (HCS). Oil-in-water cream formulations, containing 1% w/w of radiolabeled C(14) BCX-34 and propylene glycol (PG), glycerin (GLY), isopropyl myristate (IPM), oleic acid (OA) and capric-caprylic esters (CE) were prepared. Petrolatum and lanolin based ointments were also prepared with PG. Sections of the HCS, 250 microm thick, were fitted to vertical Franz diffusion chambers containing a receptor medium of pH 7.4 phosphate buffer solution maintained at 37 degrees C. Using the finite dose technique, 4-6 mg of a formulation sample was applied to the epidermal surface of each section and drug diffusion was permitted for 12 and 24 h periods. The distribution of drug into the HCS epidermis, dermis and into the receptor medium was measured by scintillation spectroscopy. The results show good correlation of the calculated in-vitro values for flux and skin-vehicle partition coefficients against the observed amounts of drug detected in the HCS. The mixed emulsion cream formulation containing PG delivered higher amounts of drug into the skin when compared to the same formulation containing GLY cream. The self-emulsifying cream formulation containing IPM had a higher skin-vehicle partition coefficient and delivered more drug into the dermis when compared to those formulations that contained OA and CE. The petrolatum ointment delivered six times more drug into the epidermis than the lanolin ointment, and had higher skin-vehicle partition values. In conclusion, creams containing PG and petrolatum-base formulations would be suitable for BCX-34 dermal delivery.
authors.affiliation: BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. tviegas@biocryst.com
authors.forename: T X
authors.initials: TX
authors.lastname: Viegas
authors.forename: L L
authors.initials: LL
authors.lastname: Van Winkle
authors.forename: P A
authors.initials: PA
authors.lastname: Lehman
authors.forename: S F
authors.initials: SF
authors.lastname: Franz
authors.forename: T J
authors.initials: TJ
authors.lastname: Franz
mesh_terms: D000465:Algorithms; D002210:Caprylates; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004058:Diffusion; D004655:Emulsions; D005079:Excipients; D006147:Guanine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D009226:Myristates; D009823:Ointment Bases; D009824:Ointments; D011409:Propylene Glycols; D012869:Skin Absorption; D012995:Solubility
chemical_list: D002210:Caprylates; D003879:Dermatologic Agents; D004655:Emulsions; D005079:Excipients; D007166:Immunosuppressive Agents; D009226:Myristates; D009823:Ointment Bases; D009824:Ointments; D011409:Propylene Glycols; C008205:isopropyl myristate; D006147:Guanine; C104194:peldesine