Research Projects

Tyrosinemia type- I, also known as hepatorenal tyrosinemia type 1 HT-1, is a genetic condition affecting the liver, kidneys, and central nervous system. The treatment involves a diet restricted in protein tyrosine and phenylalanine and daily administration of 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC), or nitisinone, lifelong. Treatment results are best when treatment is started early. The drug NTBC, also known as Nitisinone, is commercially available and used for treatment along with dietary restrictions. The FDA approved nitisinone in 2002 and 2005, and its patent expires in 2017. However, the drug is not licensed in India and is imported on a named patient basis. The objective of this study is to develop a generic NTBC for patients with genetically proven hereditary tyrosinemia 1, evaluate the efficacy and safety of indigenously manufactured generic Nitisinone, and establish the minimum dose of NTBC effective in suppressing plasma succinylacetone production. The drug will be manufactured from the active pharmaceutical ingredient API as an immediate-release hard capsule, each containing 2 mg, 5 mg, or 10 mg of Nitisinone. The drug product will be dispensed into various dosage forms using good laboratory practices and undergo rigorous quality check parameters using analytical tools like LC-MS/MS. The proposed solution aims to create a first generic, temperature stable, safe, effective, and economical NTBC formulation for patients with Hereditary tyrosinemia 1, an inborn error of metabolism, which will impact the treatment of patients and their families. Key questions addressed by this proposal include manufacturing the drugs at a significantly lower price, paving the way for licensure in India, making the consumable tablet more temperature resistant, and establishing the ideal NTBC dose after evaluating the response in patients treated.