The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

Abstract

Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection/pre-puberty/post-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations.

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

“…Although the pH of the vagina is around 4.5, it can be affected when an infection occurs, then it could reach up to 7 [ 10 , 50 ]. In the present study, the pH of the formulations was found to be within the vaginal pH conditions.…”

“…To mimic application conditions, the formulations were mixed with SVF, which was prepared by mixing NaCl 3.510 g, KOH 1.400 g, Ca(OH) 2 0.220 g, bovine serum albumin 0.018 g, lactic acid 2.000 g, acetic acid 1.000 g, glycerol 0.160 g, urea 0.400 g and glucose 5.000 g to 900 mL of distilled water in a beaker, and stirred until completely dissolved. The pH of the mixture was then adjusted to 4.5 using HCl, and the final volume was adjusted to 1 L [ 50 , 80 ].…”

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles

“…Because of cationic amino groups, CS undergoes ionic interactions with carboxylic moieties of mucins, 8 , 10 the main component of mucus layers. Introducing thiol groups on CS is a well-established strategy to increase mucoadhesive properties further.…”

Vaginal delivery of clotrimazole by mucoadhesion for treatment of candidiasis

“…The plain CTZ and SDs [in excess quantity] were placed in a glass stoppered volumetric flask containing 10 ml of simulated vaginal fluid at pH 4.5. 11 The sample was placed in an orbital shaker [CIS-24 Remi, India] at 37ᵒC and 80 rpm for 24h. 12 The samples were filtered through Whatman filter paper (#11) and were diluted appropriately in simulated vaginal fluid at pH 4.5 and assayed UV spectrophotometrically (Jasco, V-730) at 263nm.…”