Ciklodekstrini u formulacijama nesteroidnih protuupalnih lijekova

Non-steroidal anti-inflammatory drugs (NSAIDs), a group of chemically heterogeneous compounds, are among the most widely prescribed drugs commonly used to manage pain, fever and inflammatory diseases, such as rheumatoid arthritis and osteoarthritis. Beside aspirin and paracetamol, NSAIDs are weak acids with limited aqueous solubility that raises difficulties in their formulation and therapeutic action, often leading to variable oral bioavailability, delayed onset of analgesic action and increased risk of adverse gastrointestinal effects. Cyclodextrins (CDs) are mulifunctional excipients able to modify unfavourable physicochemical properties of different drugs through inclusion complex formation. For example, inclusion complexation with hydroxypropyl- y-cyclodextrin (HPyCD) enabled the development of diclofenac sodium ophthalmic solution without the need to use potentially irritant surfactants and cosolvents. By that, the incompatibility issues between the drug and benzalkonium chloride were also avoided, providing the benefits to preserve the formulation with a physiologically more acceptable compound. All this resulted in better ocular tolerance of the formulation. Inclusion complexation with hydroxypropyl- -cyclodextrin (HPCD) enabled the development of parenteral, ready to use diclofenac sodium solution, suitable for subcutaneous, intramuscular and intravenous administration. When applied as a fast-intravenous bolus, diclofenac/ HPCD solution provides faster analgesic action of the drug compared to conventional, co-solvent based diclofenac solution, that needs to be diluted and buffered prior the administration as a 30-minute infusion. Another clinically important benefit of diclofenac/HPCD solution is in a lower incidence of thrombophlebitis at the administration site. Inclusion complexation of piroxicam with CD resulted in amorphous, readily wettable and fast dissolving products. When applied orally, such complex provides much faster drug absorption with the consequent faster achievement of therapeutically active drug concentrations in the systemic circulation. All this translates into the clinically significant faster onset of drug action accompanied by a lower incidence of gastrointestinal irritation and ulceration, that normally accompanies the administration of conventional, CD free oral formulations of piroxicam. The selected examples dearly demonstrate the potential of CD to facilitate the development of novel NSAID formulations with enhanced efficiency and safety