Development of Film Coated Tablets Containing Solid Dispersions of Canagliflozin Prepared by Kneading Technique for Solubility Enhancement

Abstract

Diabetes mellitus is characterized by impaired lipid, protein, and carbohydrate newlinemetabolism, which may be caused by both inadequate insulin production and poor newlineinsulin action. Type 1 and type 2 diabetes are the two subtypes of the disease, with newlinetype 2 being the more severe. The largest cause of illness and death globally, type 2 newlinediabetes affects around 451 million individuals worldwide. Canagliflozin (CGF) is a newlinesodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 newlinediabetes. Since SGLT2 proteins are highly expressed over the proximal convoluted newlinetubules of the kidney, they have been identified as a key target for the treatment of newlinetype II diabetes mellitus. About 90% of the filtered glucose is reabsorbable, and this newlineis facilitated by SGLT-2 proteins. As a result, SGLT-2 inhibitors prevent SGLT-2 newlinereceptor activity, which lowers renal tubular glucose absorption. An oral SGLT2 newlineinhibitor called CGF, combined with dietary and activity modifications, is used to newlinetreat type 2 diabetes mellitus. The FDA initially approved it in 2013 for the treatment newlineof diabetes, and then in 2018 it was given approval for a second use-reducing the risk newlineof cardiovascular events in people with type 2 diabetes mellitus. The first oral antidiabetic newlinemedication approved for use in people with type 2 diabetes in preventing newlinecardiovascular events is CGF. According to the biopharmaceutical classification newlinesystem, CGF is a BCS class II medication with high permeability (log P = 3.09) and newlinepoor water solubility (0.0045 mg/mL). Therefore, enhancing drug dissolution in GIT newlinefor increased blood stream absorption requires increasing CGF solubility. Solid newlinedispersion technology is a molecular drug dispersion in a polymer matrix that has the newlinepotential to significantly enhance the solubility and dissolution characteristics of newlinemedications with poor solubility. DOE is a robust statistical technique for analyzing newlineproduction and process problems and optimizing product or process designs. The newlineCCD response surface methodology was chosen becau