Microemulsion assisted transdermal delivery of a hydrophilic anti-osteoporotic drug: Formulation, in vivo pharmacokinetic studies, in vitro cell osteogenic activity

ABSTRACT

Gastrointestinal adverse effects such as esophageal irritation and ulcers are the major disadvantages of the oraladministration of alendronate (ALD) and nitrogen-containing bisphosphonate. We hypothesized that the transdermaldelivery of ALD via water in oil (w/o) microemulsion might help to prevent the aforementioned side effects withoutcompromising the efficacy. The pseudo-ternary phase diagrams were constructed with varying ratios of surfactantmixture and oil to recognize the concentration range of excipients required to form a monophasic microemulsion.Globule size, morphology transmission electron microscopy, and thermal behavior differential scanning colorimetryof drug-loaded microemulsion were investigated. The in vitro permeation studies revealed significantly enhancedpermeation of ALD through microemulsion than pure solution across the rat skin (p < 0.01). In an in vivopharmacokinetic study in Wistar rats, microemulsion achieved around two folds higher bioavailability than pure drugsolution (p < 0.05) when given in equal doses (30 mg/kg). Cell viability assay with human osteoblastic osteosarcoma(MG-63) cells exhibited the positive effects of ALD microemulsion on cell growth. Moreover, alkaline phosphataseand mineralization studies proved that microemulsion as a carrier retains distinct osteogenic properties of ALD.Overall, these outcomes demonstrated that the w/o microemulsion as a transdermal carrier is a promising approach forthe effective delivery of ALD, bypassing the adverse effects associated with oral administration