Metaxalone is commercially available as a 400-mg tablet, brand name Skelaxin. This product was approved by the FDA in 1962. 6 It is interesting to note that the package insert for Skelaxin does not contain any patient dosing, pharmacokinetic, or formulation information. Nor is there an indication of whether the product should be taken with or without food. However, according to patent US 6 407 128 B1, 7 the bioavailability of Skelaxin increases if dosed with food.The purpose of this study was to evaluate the effect of pH on the dissolution behavior of metaxalone in the marketed product Skelaxin tablets. The dissolution was evaluated using United States Pharmacopeia (USP) dissolution Apparatus 2 and 3 at pHs ranging from 1.5 to 7.4. Results from these studies show that the dissolution of this product is pH dependent. At low pH (simulated gastric fluid, pH 1.5), the dissolution of metaxalone from Skelaxin tablets was less than 10% over 75 minutes; whereas, dissolution at pH 4.5 showed greater than 90% release in the same time period. These results were consistent for both Apparatus 2 and 3. This suggests that Skelaxin Tablets should be considered a delayed release dosage form. According to AHFS Drug Information 2001,8 "following oral administration of a single 800 mg dose of metaxalone, mean peak plasma concentrations are attained in 2 hours. The onset of action is usually within 1 hour and the duration of action is about 4 to 6 hours. The drug has a plasma halflife of 2-3 hours. Metaxalone is metabolized in the liver and excreted in urine as unidentified metabolites." (p. 1331) Although, there is not much information on the metabolism of metaxalone in the literature, the chemistry of the metabolic products was proposed by Bruce et al.1 Several metabolites were identified, but no further information was found in the literature about the activity of these metabolites.

Glucocorticoids are utilized for their anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback of use of glucocorticoids is that it leads to senescence and toxicity. Therefore, based on the idea that decreasing particle size allows for increased surface area and bioavailability of the drug, in the present study, we hypothesized that nanodelivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared using nanoprecipitation method. The morphological characteristics of the nanoparticles were studied under scanning electron microscope. The particle size of nanoparticles was 217.5 ± 19.99 nm with polydispersity index of 0.14 ± 0.07. The nanoparticles encapsulation efficiency was 34.57% ± 1.99% with in vitro drug release profile exhibiting a sustained release pattern over 10 days. We identified improved skeletal muscle myoblast performance with improved closure of the wound along with increased cell viability at 10 nmol/L nano-dexamethasone-PLGA. However, dexamethasone solution (1 μmol/L) was injurious to cells because the migration efficiency was decreased. In addition, the use of dexamethasone nanoparticles decreased lipopolysaccharide-induced lactate dehydrogenase release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nanoparticles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function.

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