Associação de capsaicina com anestésicos locais para aumento da analgesia

Local anesthetics (LA) are crucial in medical practice to numb parts of the body. However, LA do not allow selective blocking of nociceptive fibers and fail to anesthetize inflamed tissues. Capsaicin (CAP) is a poorly hydrosoluble compound used as an analgesic. There are reports in the literature that the injection of LA followed by CAP leads to a decrease in motor blockade in animals. LA and CAP are also used individually in topical formulations for the treatment of chronic pain. This thesis reports for the first time the analgesic effect of a drug combination (LA and CAP) on inflamed tissue and also describes the development of a topical formulation of them. In part 1 CAP was complexed with HP-ß-cyclodextrin, which increases its water solubility by 20 times. The complex was lyophilized under an optimized cycle and characterized by Differential Scanning Calorimetry, X-ray Diffraction and Scanning Electron Microscopy. These techniques provided evidence on the complexation between cyclodextrin and CAP, while Nuclear Magnetic Resonance (NMR) proved the inclusion complex formation. The lyophilized complex (resuspended in a solution with mepivacaine) was injected in mice, resulting in: i) decreased motor blockade of the sciatic nerve; ii) significant increase of anesthesia in a mechanical test, in inflamed tissue. In part 2 of this thesis, a new formulation containing exclusively the lidocaine (LA) and capsaicin was reported. The equimolar mixture of these drugs produced a liquid system at room temperature, with an amorphous pattern reported by X-ray diffraction. Infrared spectroscopy indicated intermolecular interaction between the compounds, as confirmed by NMR. This technique indicated a strong intermolecular hydrogen bond between the carbonyl (CAP) and amide (LDC) groups, which explains the reduction of the melting temperature of the components to below 25 ° C, characterizing a deep eutectic mixture. The [LDC]1[CAP]1 mixture proved to be highly stable and it increased the lipophilicity of the drugs, which may lead to improve their permeation into the skin. Both parts of this thesis have generated promises for future clinical application of the combination of drugs (LA and CAP). In Part 1, a parenteral formulation was developed that achieved desirable anesthesia effect, despite the inflammatory condition. In Part 2, the pre-formulation study provided a new topical formulation suitable for the treatment of neuropathic pain (AU)