Delivery of Erythromycin to Subcutaneous Tissues in Rats by Means of a Trans-phase Delivery System

Abstract

Topical administration of antibiotics is associated with reduced risk of systemic side-effects and alteration of gut microflora, and results in higher concentrations of antibiotics at the site of application (and so a lower dose of the drug is required). In conditions such as acne vulgaris, infiltration of the antibiotics into the infected subcutaneous layers is highly desirable. A trans-phase delivery system (TPDS), a mixture of benzyl alcohol, acetone and isopropanol, has been shown to enhance the effective transport of the antibiotic erythromycin across the epidermal barrier and enhance accumulation in the dermis. Two formulations containing N-methyl[14C]erythromycin were compared, a TPDS solution and a propylene glycol solution. They were applied to the dorsal areas of 4-6 week old Fischer rats and tissues were removed for analysis of radioactivity after 2, 4, 8, 12 or 24 h and skin was biopsied and sectioned for autoradiography. The erythromycin dissolved in the TPDS solvent mixture penetrated the stratum corneum and a relatively high concentration was maintained in adjacent tissues for up to 24 h. Penetration was very effective and the erythromycin was detected in significant amounts in the underlying muscle, various organs and later in the urine. In contrast the propylene glycol carrier, probably because of its primarily hydrophilic character, caused the erythromycin to traverse tissue barriers rapidly and appear in the urine. Microautoradiographs qualitatively revealed progressive disappearance of radioactivity from the surface; this correlated with results obtained by direct isotope counting. The route of penetration, in addition to following the interkeratinocyte spaces, seemed to include the perimeter of the pilosebaceous glands and their appendages before diffusion into the capillaries. The propylene glycol solution seemed to traverse the epidermis and the papillary and reticular dermis more rapidly, which might explain its rapid appearance in the urine. These data suggest that the different solutions penetrate the skin by different mechanisms.

Development and Validation of LC Method for the Determination of Ampicillin and Dicloxacillin in Pharmaceutical Formulation Using an Experimental Design

“…The solution stability was checked for sample preparation up to initial, 3,6,9,12,15,18,21, and 24 hours. The results obtained are well within the acceptance criteria up to 24 hours at room temperature.…”

“…A significant improvement in antibiotic activity and a reduction of the allergic and toxic reactions to ampicillin 8,9 have been obtained by topical formulations 10,11 . The advantage of transdermal delivery of hydrophilic drugs versus oral delivery lies in the molecular nature of the gastrointestinal tract (GIT) 12 . As a lipid membrane, the GIT possesses hydrophobic properties; thus, the more hydrophilic a drug is, the more likely it is to be absorbed poorly through the GIT.…”

Distribution study of peplomycin in rat kidney revealed by immunocytochemistry using monoclonal antibodies

“…Autoradiography methods, which are commonly employed for pharmacological studies on drugs, are sensitive and specific but possess drawbacks inherent in the use of a radioisotope. They also require time-consuming and complicated techniques and provide only an indirect detection system for drug localization in cells and tissues (Peng and Nimni 1999;Mountfield et al 2000). Recently, we have successfully developed immunocytochemical (ICC) procedures for detecting the cellular uptake of other water-diffusible small-molecule drugs, such as anticancer antibiotic daunomycin (DM) (Fujiwara et al 2005(Fujiwara et al , 2007Ohara et al 2007a, b) and aminoglycoside antibiotic gentamicin (GM) ).…”

Formulation development and in vitro and in vivo evaluation of membrane-moderated transdermal systems of ampicillin sodium in ethanol: pH 4.7 buffer solvent system

“…10,11 The advantage of transdermal delivery of hydrophilic drugs versus oral delivery lies in the molecular nature of the gastrointestinal tract (GIT). 12 As a lipid membrane, the GIT possesses hydrophobic properties; thus, the more hydrophilic a drug is, the more likely it is to be absorbed poorly through the GIT. Moreover, the amino group in ampicillin confers 13 an ability to cross the cell wall barrier that is impenetrable to other types of penicillin.…”