Dysphagia: daily concerns and formulative approaches for drug therapy

This doctoral thesis aimed to argue about the specific subject of dysphagia and its relative concerns. Dysphagia is defined as the sensation of delayed passage of the bolus from the mouth to the stomach and issues regarding swallowing of drug therapy are going to be discussed and faced in this work. In fact, focus was mainly pointed on the difficulty of solid oral dosage forms deglutition and, on problems related to compounding and administration of drug therapy. Two model drugs were examined: pravastatin sodium and potassium canrenoate. Their diffuse prescription makes them two interesting molecules in order to optimize alternative dosage forms with respect to the solid one. The pharmaceutical market offers a wide availability of dosage forms but solid ones are by far the most common due to some advantages that they have in terms of production, stability of the molecule, and costs. Sometimes, not all active molecules are formulated in the preferable form suitable to dysphagic people as well. Population with swallowing inability requires some specific arrangements to assume the prescribed drug therapy. Compounding commercial dosage forms is not always possible, for example in case of gastro-enteric or controlled-release formulations. Nevertheless, the lack of awareness and proper background make errors happen in the several care settings (hospital, nursing homes, long-term care facilities) where dysphagic patients are admitted. Other problems may occur during manipulation process such as, for example, invaluable drug losses, active molecule instability, palatability decrease, cross-contamination among the drug powders crushed in the same device. To overcome some issues related to drug intake in dysphagic people, the purpose of the work was to optimize compounding process in order to produce suitable dosage forms for this specific target population. The work was organized in the following parts. After a general introduction of dysphagia issue, biopharmaceutics considerations concerning drug compounding were argued in the first part of the thesis. In the second chapter, current clinical practice was dealt with. Whatever was daily performed in the hospital setting, for instance, tablet splitting to facilitate drug intake reducing tablet size, or inappropriate prescriptions of solid oral dosage forms when other therapeutic forms would be available, or occupation risks related to hospital workers during bedside compounding were discussed. The third chapter of the work addressed the optimization of some dosage forms. Liquid dispersions of pravastatin sodium and potassium canrenoate were set up and enteral delivery via feeding tubes was analyzed for both of them. Pravastatin sodium was further studied to prepare a gelified form to replace tablet. Rheological and kinetic release profile studies were evaluated. The same statin was used to refine an orodispersible film able to disintegrate in the mouth after contact with saliva. All these dosage forms, studied and tuned in the laboratory, might be able to replace commercial tablets. They might guarantee drug therapy to those who, due to their inability to swallow solid forms, would not have therapeutic alternative with the exception of extemporaneously and bedside produced preparations.