Generational shifts in Parkinson’s therapy: A review of levodopa and carbidopa formulation technologies

Although the combination of levodopa and the decarboxylase inhibitor carbidopa for over ۵۰ years has been regarded as a gold standard in Parkinson’s disease therapy, it is paradoxically limited clinically by a relatively short biological half-life and a reliance on the saturable LAT۱ transporter. In this review, we compare the pharmaceutical development to overcome these pharmacokinetic challenges to achieve continuous dopaminergic stimulation. Although immediate-release (IR) and orally disintegrating tablets (ODT) share the fast onset characteristics, they result in pulsatile plasma profiles responsible for motor fluctuations. On the other hand, modified-release oral deliveries, going anywhere from controlled-release (CR) up to extended-release (ER) and gastroretentive systems, are designed to dampen these fluctuations; they often result in erratic absorption profiles and decreased bioavailability as a consequence of variations in gastric emptying. The review highlights a growing paradigm shift for non-oral delivery systems that circumvent unpredictable gastrointestinal environments. While pulmonary powders are a form of rapid rescue via inhaled therapeutics, and enteral gels provide phenomenological stability through invasive delivery, ۲۰۲۴–۲۰۲۵ is indeed “The year of the subcutaneous revolution.” By processes of phosphate-prodrug chemistry (foslevodopa/foscarbidopa) and liquid reformulation (ND۰۶۱۲), researchers have solved the challenge of levodopa’s poor water-solubility to achieve stable non-surgical ۲۴h infusions, which are dose-formulated on steady-state pharmacology. Both liposomes and dissolving microneedle arrays hope to decouple levodopa from systemic metabolism by releasing it, coated in auto-regulating polymer or dipcote on the skin surface, through the blood-brain barrier. Finally, the evolution of formulation development is headed from mechanical enlargements of gastric residence toward chemical and nanoscopic engineering to secure sustained bioavailability.

کلیدواژه ها:

Blood brain barrier ، Drug delivery systems ، Microneedle Arrays ، Nanocarriers ، Parkinson's disease