Lornoxicam

Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (-11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 μM nimesulide as compared with 0.26-fold standard 10 μM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC₅₀ values of 0.52 ± 0.02 μM to 3.46 ± 0.13 μM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs.

Emulgel dosage form is an advanced form of transdermal drug de-livery. It is a combination of emulsion and gel in a definite ratio. Emulsions are incorporated into the gel with proper mixing. The emulsion present in emulgel can be either oil/water or water/oil, which is thickened by mixing it with a gelling agent.

On the basis of the solubility of lornoxicam in various oils, a surfactant and a co-surfactant were selected for further research. For the preparation of emulgel, the emulsion was prepared with Smix (surfactant and co-surfactant) in a ratio of 1:2. The prepared emulsion was incorporated into different concentrations of carbapol 934 in a 1:1 ratio to make a homogenous emulgel.

The emulgel was inspected visually to see if it had any phase behaviour, spreadabil-ity, or grittiness by applying it to a slide. All formulations were evaluated for pH, physical properties, drug content, spreadability, extrudability, swelling index, viscosity, and centrifu-gation. Franz diffusion cell was used to perform in-vitro release of formulation with the help of egg membrane. Among all formulations, F3 showed 83% release after 6 hours and showed acceptable physical properties like homogeneity, colour, consistency, pH value, spreadability, extrudability, and drug content.

Thus, emulgel can be regarded as a more feasible drug delivery system for hydrophobic drugs (lornoxicam) than the currently marketed formulation. Optimized emulgel formulation consists of a microemulsion of lornoxicam, 1% of carbopol 934, propylene glycol, sodium benzoate, lemon grass oil, glycerin, and distilled water. In the in-vitro release studies, pH 7.4 phosphate buffer emulgel formulation (F3) showed 83% after 6 hours. Emulgel was found to be stable under stable conditions.

The emulgel of the poorly water-soluble drug (lornoxicam) was formulated. The components and their optimum ratio for the formulation of microemulsion were obtained by solubility studies and droplet size analysis. Thus, microemulsion can be regarded as a more feasible dose delivery system for lornoxicam than the currently marketed tablet, capsule, and injection formulations. Optimized microemulsion of lornoxicam was incorporated into the gel base. Therefore, it may be concluded that emulgel of lornoxicam can be used as a controlled-release dosage form of the drug for local application in rheumatoid arthritis.