| Abstract (english) | 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. |
