W/O/W Multiple Emulsions Containing Nitroimidazole Derivates for Vaginal Delivery

Abstract

The aim of our study was to formulate a stable multiple emulsions containing two nitroimidazole derivates, metronidazole (MT) and ornidazole (OR), for vaginal therapy. MT and OR were located internal and external phases of multiple emulsion, respectively, and the in vitro release studies were realized in phosphate (pH 7) and lactate buffer (pH 4.5) solutions to investigate better the effect of pH and location of active substance on the release. The imaging studies were realized in rabbits following labeling MT and OR with Technethium-99m ( 99m Tc) to evaluate the in vivo absorption characteristics. The percentage of MT and OR released from the multiple emulsions in alkaline media were 3.2-and 2.8-fold greater than that observed in acidic media, respectively, when they were introduced in the internal phase of the multiple emulsions. The absorption rate of MT from vaginal epithelium was faster than OR. We observed that especially in alkaline medium a high release was found that was convenient for the vaginal infections seen in the alkaline pH. We concluded that W/O/W multiple emulsions were locally effective in vagina and they could be introduced as a new drug carrier system for vaginal delivery.

Recent Advances in Nanosystems and Strategies for Vaginal Delivery of Antimicrobials

“…Özer et al, in 2007, formulated two multiple emulsions containing metronidazole and ornidazole in different aqueous phases, monitoring both drug release in acidic/alkaline medium to understand the role played by pH on the release. A proper release was observed in alkaline medium, which is convenient for vaginal infection, and both the systems were found to be locally effective in the vagina [38].…”

Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels

“…Multiple emulsions are a specific case of emulsion systems whose manufacturing requires both lipophilic and hydrophilic surfactants (see Table 5 ). A non-ionic silicone based Abil EM 90 W/O emulsifier is the most commonly used lipophilic surfactant in the formation of internal emulsion, while a hydrophilic surfactant, e.g., poloxamer 407 provides w/o/w multiple emulsion stability by encapsulation of w/o emulsion in external aqueous phase [ 89 , 101 , 102 , 103 , 104 ]. In turn, obtaining SEDDS formulations is a difficult process due to the limited number of oil-surfactant combinations capable of forming these systems (see Table 6 ).…”

“…In multiple emulsions and SEDDS-type systems ( Table 5 and Table 6 ) the addition of gelling polymers is limited [ 89 , 106 ] as minor addition of an electrolyte into the internal aqueous phase of a multiple emulsion often increases the viscosity of the formulation [ 125 ]. The electrolytes influencing the stability and rheological properties of vaginally administered multiple emulsions include magnesium sulphate or sodium chloride [ 89 , 102 , 104 ].…”

Drug-Core Double Emulsions for Co-release of Active Ingredients

“…As research show double emulsion could contain such as sodium lactate, spironolactone and chlorhexidine digluconate in W/O/W double emulsion [7]. Encapsulation and release of metronidazole with ornidazole in internal and external phases of W/O/W emulsion for vaginal delivery were investigated by Özer et al [8].…”

“…As research show double emulsion could contain such as sodium lactate, spironolactone and chlorhexidine digluconate in W/O/W double emulsion [7]. Encapsulation and release of metronidazole with ornidazole in internal and external phases of W/O/W emulsion for vaginal delivery were investigated by Özer et al [8].The modern microencapsulation technology of bioactive substances is an important formulation strategy to multidrug therapies being involved into advanced drug delivery systems. Multidrug therapy was first proposed to the treatment of tuberculosis and is practice widely adopted against AIDS and cancer.…”