Acute and subacute dermal toxicity analysis of film forming topical spray of meloxicam: in vitro and in vivo studies

Meloxicam is used in the treatment of clinical mastitis to promote milk production. Therefore, in the present investigation, acute and sub-acute dermal toxicity of our prototype film-forming topical dermal spray of meloxicam was carried out in addition to the dermal permeation rate. Implementing the OECD test norms, acute and repeated dose analyses were carried out in male and female groups of rats. Film-forming topical dermal spray of meloxicam released 68.62% of the drug over a 24-h period with a permeation rate of 22.58-µg/cm2. The lethal dose 50 (LD50) for film-forming topical dermal spray of meloxicam may be considered to be >2000 mg.kg−1. Various hematological, biochemical and histopathological parameters were examined post-treatment in sub-acute toxicity. Film-forming dermal spray of meloxicam at low and moderate doses did not exhibit any adverse effects on the skin and mammary glands whereas the high dose had shown hyperplasia in the tubuloalveolar area of mammary glands. Hence, the"no observed adverse effect level (NOAEL) was considered to be 1000-mg.kg−1 in experimental animals. The IC50 value for blank film-forming topical dermal spray and meloxicam film-forming topical dermal spray was found to be 2.655-µg/mL, and 1.871-µg/mL, respectively, as compared to 229.18-µg/mL of meloxicam solution at 72 h against normal breast epithelial, MCF-10A cells. Hence, meloxicam film forming dermal spray retains the normal breast epithelial cell viability at low to moderate doses in both in vitro and in vivo applications. In conclusion, the moderate dose of film-forming dermal spray of meloxicam was found to be safe for topical use.