Microenvironmental pH Modification in Buccal/Sublingual Dosage Forms for Systemic Drug Delivery

Many drug candidates are poorly water-soluble. Microenvironmental pH (pH_M) modification in buccal/sublingual dosage forms has attracted increasing interest as a promising pharmaceutical strategy to enhance the oral mucosal absorption of drugs with pH-dependent solubility. Optimizing drug absorption at the oral mucosa using pH_M modification is considered to be a compromise between drug solubility and drug lipophilicity (Log D)/permeation. To create a desired pH_M around formulations during the dissolution process, a suitable amount of pH modifiers should be added in the formulations, and the appropriate methods of pH_M measurement are required. Despite pH_M modification having been demonstrated to be effective in enhancing the oral mucosal absorption of drugs, some potential risks, such as oral mucosal irritation and teeth erosion caused by the pH modifiers, should not been neglected during the formulation design process. This review aims to provide a short introduction to the pH_M modification concept in buccal/sublingual dosage forms, the properties of saliva related to pH_M modification, as well as suitable drug candidates and pH modifiers for pH_M modifying buccal/sublingual formulations. Additionally, the methods of pH_M measurement, pH_M modification methods and the corresponding challenges are summarized in the present review.